Comparison of Bioactive Glass Synthetic Bone Graft Particles and Open Debridement in the Treatment of Human Periodontal Defects. A Clinical Study Stuart J. Froum,*' Mea A. Weinberg,' and Dennis Tarnow*^ THE PURPOSE OF THIS STUDY was to compare the repair response of bioactive glass synthetic bone graft particles and open debridement in the treatment of human periodontal osseous defects. Fifty-nine delects in 16 healthy adults were selected. Each patient had at least 2 sites with attachment loss of at least 6 mm with clinical and radiographic evidence of intrabony or furcation defects. One to 3 months after causerelated therapy (oral hygiene instructions, scaling and root planing), the following measurements were recorded prior to surgery: probing depths, clinical attachment level, and gingival recession. Each defect was surgically exposed and measurements made of the alveolar crest height and base of osseous defect. The test defects were implanted with bioactive glass. The other sites served as unimplanted controls. Flaps were sutured at or close to the presurgical level. Radiographs and soft tissue presurgical measurements were repeated at 6, 9, and 12 months. At 12 months all sites were surgically re-entered to record osseous measurements. At the 12-month evaluation, significantly greater mean probing depth reduction was noted in the bioactive glass group compared to the controls (4.26 mm versus 3.44 mm; P = 0,028). Clinical attachment level gain was significantly improved (P = O.(XX)4) in the bioactive glass sites {2.96 mm) compared to the control sites (1.54 mm). There was significantly less gingival recession in the bioactive glass sites (1.29 mm) compared to the control sites (1.87 mm). Defect fill was significantly greater in the bioactive glass sites (3.28 mm) compared to the control sites (1.45 mm). Defect depth reduction was significantly greater in the bioactive glass sites (4.36 mm) compared to the control sites (3.15 mm). In conclusion, bioactive glass showed significant improvement in clinical parameters compared to open flap debridement. J Pcriodontol 1998:69:698-709. Key Words: Grafts, bone; bone regeneration; periodontal diseases/surgery; periodontal diseases/therapy; glass, bioactive; surgical flaps. Periodontal surgical procedures have focused on the elimination of hard and soft tissue defects (i.e., probing depths and osseous defects) by regenerating new attachment. This new attachment ideally consists of new bone, cenientum. and attached periodontal ligament to replace that which was lost due to periodontal disease. Toward these ends a variety of materials and regenerative procedures have been utilized.' Many of these procedures include the use of bone grafts and bone replacement materials. A re- *New York University. Department of Implant Dentistry, New York. NY. Departmcn! of Surgical Sciences (Periodontics). cent review focused on the clinical and histological results following the use of bone autografts and allografts.: In their conclusions, the authors state that " . . . conclusive evidence now exists that some regeneration occurs after regenerative procedures in which bone grafts are used." Although the use of intraoral autogenous bone grafts is well accepted in the periodontal community, drawbacks such as limited availability of donor sites, requirement for an additional surgical procedure to obtain the graft material, and elimination of potential sites for the placement of dental implants are recognized limitations with this material. Volume M Number 6 FROl M, WEINBERG. TARNOW 699 Furthermore, although allografts obtained from an approved bone bank have been shown to be free of human immunodeficiency virus,1 questions have been raised as to the osteogenic potential of commonly used allografts.1 This has renewed interest in evaluating alloplastic materials as bone replacement grafts in treatment of intraosseous defects. A variety of alloplastic materials have been utilized in periodontal therapy.1 Positive clinical results for probing depth reduction and "till" of defects have been well documented. In clinical studies, an alloplastic material (porous hydroxyapatite) was compared to the most commonly used allografl (decalcified freeze-dried bone) with no statistical difference in results of the parameters measured (probing depth reduction and fill of the osseous defects)."1 However, to date, use of any of the reported alloplast materials has not resulted in histological evidence of new attachment. Materials such as porous hydroxyapatite (HA).* a calcium coated polymer alloplastic material,11 and tricalcium phosphate1"" when placed in human periodontal defects have demonstrated osseous fill and probing depth reduction, but show limited evidence of new connective tissue attachment. Bioactive glass1 has the ability to bond to both hard and soft tissue. The composition of bioactive glass particles is silicon dioxide (46 mole %). sodium oxide (24.4 mole 9c)% calcium oxide (26.9 mole %), and phosphorous pentoxide (2.6 mole %).12 Several animal studies have demonstrated advantages of hioactive glass compared to HA. In u Patus monkey surgical model, the clinical and histologic repair response of 45S5 bioactive glass, dense HA, tricalcium phosphate, and open debridement were compared. Two-walled defects were surgically created. The animals were sacrificed at I, 4. and 6 months. The bioactive glass implanted sites showed significantly less junctional epithelium migration, stopping at the level of the material and bone formation around the particles by 4 months. The HA sites showed more junctional epithelium migration. The HA particles were not consolidated and were embedded in connective tissue." This study also found bioactive glass to be easier to handle and manipulate than the other materials. Bioactive glass has been used in humans to treat conductive deafness, alveolar ridge resorption, and bone loss due to periodontal disease." A recent study in humans compared bioactive glass panicles and flap debridement in the treatment of 12 pairs of interproximal intrabony periodontal defects in 12 patients. Six-month re-entry results demonstrated significantly greater gains in clinical attachment level (2.6 ± 1.49 mm test, 1.0 ± 0.75 mm control) and in hard tissue fill (1.75 ± 1.08 mm test, 0.04 ± 0.50 mm control) with the bioactive glass (test) than with the flap debridement (control) group (unpub- :PerioGlas. Block Drug, Inc.. Jersey City, NJ. lished data). Case report evidence of 37 sites utilizing bioactive glass, bioactive glass and autogenous bone, and bioactive glass and decalcified freeze-dried bone was recently published.1? The authors reported a 6-month mean probing depth reduction of 53%, 57%, and 53%, respectively and mean gains in probing attachment level of 5.3 mm, 4.S mm, and 5.6 mm. No re-entries or controls were included in the results. A recent clinical study compared bioactive glass and open flap debridement in the treatment of 44 periodontal intrabony defects in 20 patients. The authors measured plaque scores, bleeding scores, probing depth (PD) and clinical attachment level (CAL) ,n baseline, 3, 6, 9, and 12 months postsurgery. Standardized radiographs for computer-assisted densitometric image analysis (CADIA) were taken at baseline, immediately post-operatjvely and at 1 year. The authors reported that PD and CAL showed significant improvement in the experimental and control sites, "with a greater trend to improvement in experimental sites." A significant increase was reported in radiographic density and volume in favor of the bioactive glass treated sites when compared with the open debridement treated sites with CADIA analysis. No surgical reentries were performed." The present investigation was designed to clinically evaluate bioactive glass material and compare it to the open debridement controls in the treatment of human periodontal osseous defects. MATERIALS AND METHODS Patient Population Sixteen patients (8 males, 8 females: mean age, 43 years) were selected from those requiring routine periodontal therapy in the Department of Periodontics at New York University Dental Center. Each patient signed an informed consent form after the nature of the study was explained to them. Each patient was told that they could withdraw from the study at anytime without jeopardizing their rights to proceed with dental care at the Dental Center. The study and informed consent were accepted by the human research committee at New York University Dental Center prior to initiation of the study. Each patient selected for the study satisfied the following criteria: I. No medical problems that would contraindicate routine periodontal surgery. 2. Two or more sites in different quadrants with attachment loss ^ 6 mm. These •>itcs e x h i b i t e d clinical and radiographic evidence of intrabony or furcation defects. 3. Patients who had not taken antibiotics within 6 months of initial examination and did not require antibiotic premedication for any systemic condition. 4. No allergy to either tetracycline or chlorhexidine. 700 BIOACTIVE GLASS BONE GRAFT IN HUMAN PF.RIODONTAL LESIONS J Penodomol June 1998 Initial Therapy and Measurements Each patient had undergone cause-related therapy at least 1 to 3 months prior to enrollment in ihe study. This consisted of scaling, root planing, oral hygiene instruction, and occlusal adjustment where indicated. Prior to surgery, a customized acrylic stent was fabricated for each patient and stored on the study cast to minimize distortion. The stent was grooved in an occlusal apical direction with a tapered bur so that the silver point was returned to the same position for each successive measurement. Measurements for gingival recession probing depths and clinical attachment levels were recorded from a fixed reference point (stent) to the nearest 0.01 mm using a digital Boley gauge, silver point, and locking pliers.17 All measurements were recorded by a single investigator. Local site scores were recorded for: 1) plaque index (PI);1" 2) gingival index (GI);1" 3) gingival recession (Rec); 4) probing depth (PD); 5) clinical attachment level (CAL); and 6) mobility.*1 All of the above measurements were recorded for each test and control tooth. Measurements were recorded from: 1) stent to cemento-enamel junction (CEJ); 2) stent to gingival margin; and 3) stent to deepest probing depth at the test sites. Only when the patient demonstrated adequate plaque control (no visible plaque around all surfaces of the test and control teeth) was surgery performed. At time of surgery following flap reflection, the following measurements were recorded: 1) stent to CEJ (to test for seating of the stent); 2) stent to alveolar crest; and 3) stent to base of defect. Values for osseous defect depth were calculated by subtracting "stent to alveolar crest" from the measurement of "stent to base of defect" for each defect. Intrabony defect classification 1, 2, 3, or a combination was recorded. Classification of furcation defect (I, II, III) was also determined following defect and root debridement. Clinical soft tissue measurements were repeated at 6, 9, and 12 months by the same investigator, utilizing the same instruments and stent. Measurements for PI, GI, and mobility were repeated prior to re-entry surgery at 12 months. All sites were re-entered 12 months postsurgery and all hard tissue measurements recorded utilizing the same technique. Values for crestal resorption were calculated by subtracting the initial measurement of "stent to alveolar crest" from the measurement of "stent to alveolar crest" obtained at the time of re-entry surgery. Defect fill was calculated for each defect by subtracting the measurement of "stent to base of osseous defect" at initial surgery from the measurement of the same site repeated at reentry. Radiographs and photographs were taken presurgically and just prior to re-entry. Additional photographs were taken at each postsurgical appointment to document the healing response. Surgical Protocol One to 3 months following cause-related therapy, surgery was performed. Sites were selected by the flip of a coin and designated as test (t) or control (c). Additional sites in the same quadrant (if present) were treated with the same modality. Following measurements and administration of local anesthesia, all sites were treated via reflection of a full thickness mucoperiosteal flap attempting to retain all soft tissue. Following flap reflection, all accretions were removed from the root with hand and ultrasonic instruments. Defects were debrided and wherever there was no observable intramarrow bleeding, small penetrations were made with a 1/2 round bur or curet tip. All defects were irrigated with saline. The control sites were then sutured with interrupted sutures using 4-0 silk.5 The test sites were treated in the same manner. However, following debridement of the root and bone defect, the bioactive glass replacement graft material was utilized to fill the defects to the most coronal level of the osseous walls. No osteoplasty/ostectomy was done on any control or test treated defects at time of initial surgery. The alloplast (bioactive glass) was prepared in the mixing cup provided by adding 4 to 6 drops of saline or sterile water until the mixture was paste-like in consistency. Working time was approximately 2 to 3 minutes as indicated by the manufacturer. All patients received systemic tetracycline HC1 1 gm/ day for 14 days postsurgery and were instructed to rinse with 0.12% chlorhexidine gluconate twice daily until the sutures were removed. Patients were seen 7 days postsurgery for suture removal (two patients returned at 10 and 14 days postsurgery for suture removal following one area of surgery in each patient). Patients were instructed in home care procedures including the continued use of 0.12% chlorhexidine rinses twice daily for 2 weeks, brushing, and flossing. Patients were seen weekly for 6 weeks, then monthly for the next 10 Vi months. At each visit oral hygiene was reinforced and the surgical sites professionally debrided by the same investigator (MAW). Prior to professional debridement at the 6- and 9-month recall appointments, soft tissue measurements were recorded. Twelve months postsurgery, re-entry surgery was performed at the test and control sites at which time measurements were repeated. Re-entry surgery included procedures to treat any remaining osseous defects at the experimental or control sites with appropriate therapy. 'Ethicon Inc.. Somerville, NJ. Volume 69 Nunities- h FROUM, WEINBERG, TARNOW 701 Statistical Methods Data consisted of individual site measurements of probing depth, clinical attachment level, and gingival recession at baseline and 6, 9, and 12 months postsurgery. Individual site measurements were recorded for osseous depth, crestal resorption, and defect till at baseline and 12 months postsurgery. Mobility and scores for PI and GI were assessed at baseline and 12 months postsurgery for each of 59 sites clustered in 16 patients. Each patient had at least 2 sites treated (range: 2 to 10 sites), with at least one site assigned by the flip of a coin to debridement and at least one site assigned to bioactive glass. Additional adjacent sites received the same treatment assigned to that quadrant. A 2-group randomized block analysis of variance (ANOVA) with patients considered as randomized blocks was used to compare mean change from baseline per individual site in soft tissue and osseous outcome measurements between the debridement and bioactive glass treatments both with and without covariance adjustment for respective baseline measurements of probing depth and osseous depth. This analysis accounted for potential correlation among multiple debridement and bioactive glass site measurements clustered within individual patients. For each outcome measurement, least-squares (LS) means, standard errors (SE), and 95% confidence intervals (Cl) were estimated for all observation times and for change from baseline at each postsurgery observation time. (LS-means are means which have been weighted to account for the variable number of teeth assessed in control or test quadrants in each subject. As such the LSmean for change from baseline at a given observation time will not necessarily be the exact difference between the baseline LS-mean and the LS-mean for that observation time). Differences between treatments in change from baseline were also estimated for each observation time along with corresponding standard errors and 95% CIs. An indicator variable distinguishing between vertical defect and bifurcation sites was considered as covariate within the randomized block ANOVA framework to determine if change from baseline and differences in change from baseline between treatments depended on defect type (i.e., by testing for interaction between defect type and treatment effects). Repeated measures ANOVA. with the patient again considered as a randomized block and observation time postsurgery considered as a repeated factor, was used to determine if differences in change from baseline between treatments depended on time (i.e., by testing for interaction between observation time and treatment effects). Changes in each patient's gingival index from baseline were assessed by first computing the mean change per patient for each treatment. The per patient estimates of change from baseline for each treatment were analyzed separately and also compared between treatments using the Wilcoxon signed rank test. Table 1. Summary of Mobility, Plaque Index, and Gingival Index Determined :ii Baseline and 12 Months Clinical Parameter Mobility Initial 12-month 12-month change Plaque Index Initial 12-month 12-month change Gingival Index Initial 12-monlh 12-montli change Control (n = 16 patients) Mean 1.05 0.90 -0.15 0.32 0.57 0.25 0.46 0.37 -0.09 SD 0.56 0.57 0.62 0.47 0.88 0.77 0.49 0.50 0.45 Test in = 16 patients) Mean 1.05 0.81 -0.24 0.31 0.45 0.14 0.37 0.29 -0.08 SD 0.64 0.52 0.54 0.47 0.80 0.80 0.45 0.40 0.41 Signed Rank P Value* 0.951 0.570 0.443 1.000 1.000 1,000 l.(XH) 0.500 1.000 value nol significant. Table 2. Summary of Mean Soft Tissue Measurements at Baseline and 6 Months Clinical Parameter Initial PI) 6-momh PD (vmonth change in recession 6-month CAL 6-month change in PD Control (n = 27 siles) LSMean 7.31 4.17 1.59 1.46 3.12 SE 0.32 0.29 0.16 0.24 0.26 Test (n = 32 sites) 1 S Mk.MII 7.7S 3.78 1.05 3.19 4.11 SE 0.30 0.27 0.15 0.23 0.24 ANOVA P Value 0.266* 0.309* 0.017* 0.0001 0.006 *Not significant. Significant. RESULTS Fifty-nine intraosseous defects in 16 patients were treated, 32 test sites and 27 control sites. There were no significant differences in PI, GI, or mobility from baseline to 12 months postsurgery in either the debridement or bioactive glass treatment sites nor between the 2 groups. Nor did changes from baseline differ significantly between debridement and bioactive glass sites (Table 1). There were no significant differences (P = 0.266) in the initial probing depths within both the bioactive glass and debridement treatment groups with a mean of 7.78 mm for the bioactive glass sites and 7.31 mm for the debridement sites. 6-Months Postsurgery {Table 2) The mean change in gingival recession from baseline to 6 months postsurgery was significantly lower in the test sites (1.05 mm) compared to the control sites (1.59 mm). There was a statistically significant (P = 0.006) mean reduction in probing depths at the test sites (4.11) compared to the control sites (3.12 mm). Probing depth was less in the test than in the control sites (3.78 mm versus 4.17 mm) but the differences were not statistically sig702 BIOACTIVE GLASS BONE GRAFT IN HUMAN PERIODONTAL LESIONS J Periodonlol June 1998 1.1 hli- .1. Summary of Mean Soft Tissue Measurements at Baseline .IIHI *> Months Clinical Parameter Initial PD 9-montb PD 9-month change in recession 9-month CAL 9-month change in PD Control (n = 27 sites) LSMean 7.31 3.98 1.54 1.74 3.31 SE 032 0.24 0.16 0.27 0.28 Test (n = 3 LSMean \ ^ 3.30 1.24 3.31 4.66 2 sites) SB 0.30 0.23 0.16 0.26 0.27 ANOVA P Value 0.266* 0.040* 0.174' 0.0001' 0.0007- •Not significant. 'Significant. Table 4. Summary of Mean Soft Tissue Measurements at Baseline and 12 Months Clinical Parameter Initial PD 12-month PD 12-month change in recession 12-month CAL 12-month change in PD Control In = 27 sites) LSMean 7.31 3.52 1.87 1.54 3.44 SE 0.32 0.24 ii l; 0.28 0,27 Test (n = 32 sites) LS Mean 7.78 3.48 1.29 2.96 4.26 SI 0.30 0.23 0.15 0.26 0.26 ANOVA P Value 0.266* 0.891* 0.008' 0.0004 0.028' *Not significant. Significant. nificant. Results were similar when mean change from baseline was adjusted for baseline probing depth. There was also a significant (P = 0.0001) clinical attachment gain in the test sites (3.19 mm) compared to the control sites (1.46 mm). 9-Months Postsurgery (Table 3) The mean change in probing depths from baseline to 9 months postsurgery was significantly (P = 0.0007) greater in test sites (4.66 mm) compared to debridement sites (3.31 mm). There was a statistically significant (P = 0.0001) clinical attachment gain from baseline in the test sites (3.31 mm) compared to the coniiol sites (1.74 mm). The amount of gingival recession between groups was statistically different (1.24 test versus 1.54 control). Probing depth was less in the test compared to the control sites (3.30 mm versus 3.98 mm), but the differences were not statistically significant. Results were similar when mean change from baseline was adjusted for baseline probing depth. Soft Tissue Changes 12-Months Postsurgery (Table 4) There was a statistically significant (P = 0.028) greater mean reduction in probing depth at the test sites (4.26 mm) compared to the control sites (3.44 mm). The mean gain in clinical attachment level from baseline was significantly (P = 0.0004) greater at the test sites (2.96 mm) compared to the control sites (1.54 mm). The mean change in the recession from baseline was significantly (P = 0.008) less in the test sites (1.29 mm) compared to the control sites (1.87 mm). Probing depth was not significantly different in the test versus the control group. Results were similar when mean change from baseline was adjusted for baseline probing depth. Figures 1 and 2 illustrate preoperative and 12-month control and test sites, respectively. Osseous Changes 12-Months Postsurgery (Table 5) Mean fill of the osseous defects was significantly greater (P = 0.0001) in the test sites (3.28 mm: 62.0%) compared to the control sites (1.45 mm; 33.6%). The mean reduction in osseous depth from baseline to 12 months was significantly (P = 0.0001) greater in the test sites (4.36 mm) compared to the control sites (3.15 mm). The mean change in crestal resorption from baseline to 12 months was significantly (/> = 0.0005) lower in the test sites (1.06 mm) compared to the control sites (1.69 mm). Results were similar when mean change from baseline was adjusted for baseline osseous depth. Differences in mean change from baseline between the control and test sites did not depend on defect type (i.e.. no significant interaction between defect type and treatment effects were observed). Mean residual osseous depth was not significantly different between the test and control group (Figs. 3 and 4). Bifurcations Versus lntraosseous Defects, 12-Months Postsurgery (Table 6\ Separating the data according to the type of defect treated (furcation or intraosseous defect) at 12 months demonstrated differences in healing responses. Furcation defects at 12 months showed no statistical difference in any soft tissue parameters. Osseous re-entry results showed significant advantage in osseous fill (2.59 mm test versus 0.84 mm control) and percent defect fill (55.6% test versus 15.4% control). In contrast, intraosseous defect results at 12 months showed significant advantage in recession (1.47 mm test versus 2.06 mm control), gain in clinical attachment (2.96 mm test versus 1.46 control) and change in probing depth (4.43 mm test versus 3.56 mm control) of the test versus control measurements respectively. Twelve-month re-entry results revealed significant advantages with the test group in crestal resorption (1.17 mm test versus 1.76 mm control), fill of the defect (2.84 mm test versus 1.09 mm control), and change in osseous depth (4.58 mm test versus 3.28 mm control). Differences in 12-month osseous defect depth between test and control groups were not significant. DISCUSSION This study compared the repair response of periodontal osseous defects treated by flap debridement with and V ulumc 69 Number f> FROHM, WEINBERG, TARNOW 703 Figure I. A. (lop) Preoperative probing of the control site (X.4X mm), maxillary left first molar. B. (center). Preoperaiive osseous depth of the control site is 5.63 mm. By a flip of the coin the control site received debridement alone and the t!t\ps were closed with interrupted sutures, (". (bottom). Control sire at 12-month re-entry. Reduction of osseous depth was 1.24 mm with n 4W'i /til oj the defect. Figure I. {Continued) D. {topi Preoperative radiograph of the control site, mesial aspect of the maxillary right first molar. E. (bottom). Rudiograph taken 12-months postsurgery of the control «r< without the implantation of a bioactive glass alloplastic graft. Measurements at 6, 9, and 12 months postsurgery demonstrated significantly better soft tissue responses in the graft treated sites. Mean gain in clinical attachment level and probing depth reduction was significantly better in the bioactive glass sites than in the control 6 and 9 months postsurgery. This advantage was also evident 12 months postsurgery, where gain in clinical attachment levels (2.96 mm versus 1.54 mm) and probing depth reduction (4.26 mm versus 3.44 mm) showed a statistically significant difference between test and control sites, respectively. In addition at all time periods, there was significantly less postsurgical gingival recession in the test versus control group and at 12 months it was 1.29 mm versus 1.87 mm. Although initial and 12 months probing depths showed no statistical difference between the groups, the greater reduction in PD in the test group was the result of a greater gain in clinical attachment compared to a greater postsurgical gingival shrinkage that took place in the control group. The hard tissue results followed similar trends. The 12-month re-entry measure7( 14 BIOAl TIVK CLASS HONE GRAKT IN HI MAN PERIODONTAL LESIONS J Penodontol June 1998 Figure 2. A. Preoperativt probing of test site 16.04 mm), disml aspect qf the nuixilhiry right first molar. Figure 2C. Test site at 12-month re-entry. Reduction of osseous depth was 4.62 mm, with a 659c fill of the defect. I igure 2H. Preopeniiive osseous depth of the resi site wits 6.33 mm ments demonstrated a significantly greater mean osseous till (3.28 mm versus 1.45 mm) and mean defect depth reduction (4.36 mm versus 3.15 mm) in the bioactive glass versus control sites. These values were significant at the 0.0001 level of confidence. Defect fill of bioactive glass was 62.0% versus 33.6% for open debridement. Again there was significantly less mean crestal resorption in the bioactive glass sites (1.06 mm) versus the open debridement sites (1.69 mm). The results of the present study are consistent with Garrett's assessment that "In controlled clinical trials treating furcation defects and intraosseous defects non-absorbable Figure 2l> (lop). Preoperathe radiograph of the test site, distal aspect of the maxillary right first motor. E (bottom). Radiograph taken 12- months posisurgery of the test site. Volume 69 Number 6 FROt M. WKINBERC, TARNOVV 705 and absorbable synthetic graft materials have consistently demonstrated clinical advantages beyond that achieved by debridement alone.""' Studies cited by Garrett comparing bone replacement graft and flapi debridement demonstrate a greater reduction in probing depth, less postsurgical gingival recession, and greater till of the osseous defect with porous hydroxyapatite,- non-porous hydroxyapatite,2'24 porous calcium carbonate.^ and composite graft tricalcium phosphate and doxycycline than in open debridement controls.-" The same trends were reported in clinical comparison studies with a calcium coated polymer (great- Tabk' 5. Summary of Mean Osseous Defect Measurements at Baseline :unl 12 Months Clinical Parameter Iniliul OD* 12-month OD 12-month crcst;il rcsorption 12-month defect fill 12-month ehanne m Ol> Percent defect 611 Control (n - T l.SMcan 4.34 1.19 1.69 1.45 3.15 33.60 ' sites) SE 0.23 0.16 0.12 0.18 0.19 3.40 Test (n = 32 LSMi-. ui 5.42 1.06 1.06 3.28 4.36 62.0 sites) SI. 0.22 0.15 0.12 0.17 0.18 3.30 AN< IV \ P Value 0 (K) 1 0.536' 0.0005: 0.0001' 0.0001' 0,0001' *OINCI>US depth. 'Not significant. 'Significant. er probing depth reduction and fill of the osseous defect), however, with no significant difference in postsurgical recession.^-* Other clinical human studies utilizing nonporous hydroxyapatite with re-entry ranging from 6 to 9 months showed 3 to 7 times the defect fill with the alloplast when compared with flap debridement."" " Kenney et a), reporting on 6 months re-entry results of 15 porous hydroxyapatite grafted sites versus 15 open debridement treated sites in the same individuals showed significantly better results in the grafted sites.'-' Comparison of grafted versus control sites documented defect fill of 3.5 mm versus 0.7 mm, probing depth reduction of 4.3 mm versus 2.5 mm and gain in clinical attachment of 3.6 versus 1.2 mm, respectively.1' While the same clinical superiority of the grafted (bioactive glass) versus the open debridement control is evidenced in the present study, our results with debridement treated sites appear to be better than in the studies cited above. In the present study, defect fill at 12-month re-entry measured 33.6% of the initial defect with open debridement. This is comparable to the defect fill of 34.4% reported previously when 31 defects in 19 patients were treated with open flap debridement and re-entered 24 to 28 weeks postsurgery.17 In both studies, measurements were performed by the same individual using the same measurement techniques described in the Table 6. Bifurcation Versus Intraosseous Defects 12-Months Po.stsurgi.Tj Control Test ANOVA Clinical Parameter Bifurcation Defect Initial PD 12-month PD 12-month change in RKC 12 month CAL 12-month change in PD Initial OD* 12-month OD 12-month crcstal RES 12-month defect till 12-month change in OD 12 month percent detect fill Intraosseous Defect Initial PD 12-month PD 12-month change in REC 12-month CAL 12-monlh change in PD Initial OD 12-monlh OD 12-month crestal RES 12-month defect fill 12-month change in OD 12-month percent defect fill 'Osseous depth. Not significant, 'Significant. LS-Mean n 7.00 3.99 0.97 1.91 2.91 4.69 2.09 1.44 0.84 2.59 15.4 n 7.37 3.41 2.06 1.46 3.56 4.28 0.99 1.76 1.09 3.28 24.6 SE = 4 1.16 0.87 0.55 1.02 1.00 0.85 0.56 0.46 0.66 0.68 12.5 = 23 0.40 0.30 0.19 0.35 0.35 0.29 0.19 0.16 0.23 0.23 4.3 LS-Mean n 7.31 4.16 0.69 2.90 3.66 4.93 1.39 0.63 2.59 3.54 55.6 7.90 3.29 1.47 2.96 4.43 5.52 0.93 1.17 2.84 4.58 51.8 Si' = 5 1.06 0.79 0.50 0.93 0.42 0.78 0 - 0.42 0.60 0.62 11.5 = 27 0.41 0.31 0.19 0.36 0.36 0.30 0.20 0.16 0.23 0.24 44 P Value 0.802' 0.837' 0.593' 0.304' 0.430 0.761 • 0.190' 0.069' 0.007= 0.1441 0.002= 0.264' 0.744' 0.012' 0.00071 0.037' 0.0008' 0.792' 0.003' 0.0001' 0.0001 = 0.0001' 706 B1OACTIVE GLASS BONE GRAFT IN HUMAN PERIODONTAL LESIONS J Periodontol June 1998 Figure 3 A. Preoperative probing of the control site (7.42 mm), mesial aspect of the numdibular right second molar. Figure 3C. 12-month re-entry of the control site. Reduction of osseous depth was 3.66 mm with a 30% fill of the defect, present study. Frequent professional supportive therapy may have contributed to the improved results seen in these studies. A correlation between the number of postsurgical visits and improved clinical parameters was previously documented." Initial PD between treatment and control was greater in the test group (7.78 mm) than in the control group Figure 3B. Control site debrided. Clinical view of the debrided 2-walled imrabony defect on the mesial aspect of the mandilndar right second molar. Preoperative osseous depth of the control site was 4.96 mm. (7.31 mm), but this difference was not statistically significant. The initial osseous depth of the test group (5.42 mm) and the control group (4.34) did differ significantly. However this difference did not impact our statistical findings of improved clinical values for the treatment group because the same results were obtained after covariate adjustment for initial probing and osseous depths. Moreover, often times the deepest areas of probing depth did not correspond with the depth of osseous defect.17 It was also interesting to note that when the clinical results were calculated according to type of defect (furcation or intraosseous). differences in test versus control soft tissue results did not mirror the hard tissue findings. In fact with furcation defects at 12 months postsurgery, there was no statistical difference in any of the soft tissue parameters between test and control groups. Hard tissue results did demonstrate a significant difference in defect fill and percent defect fill. Twelve-month results in the treatment of intraosseous defects did show statistical differences in gingival recession, gain in clinical attachment, and change in probing depth in favor of grafted sites. These advantages occurred concomitantly with hard tissue results including less crestal resorption, greater rill, greater percent defect fill, and greater change in osseous defect with the grafted versus the open debridement group. The small sample size of furcation defects (5 test, 4 control compared to vertical defects 27 test, 23 control) would make comparisons difficult. However, the defect type, furcation or vertical, may have mediated an altered response. It would appear that Class II furcations show a more favorable osseous response when treated with the Volume 69 Number fi FROUM, WEINBERG, TARNOW 707 Figure 4A. Preoperalive probing of the test site 19,50 mm), mesial aspect of the mandihuhir left second molar. | Figure 4C. 12-month re-entry of lest site. Reduction of osseous depth was 4.28 mm with a 70% fill of ike defect. bioactive glass material. This is in agreement with Kenney et al." and Pepelassi et a!.:is Percent fill in the latter study was 62% with a composite allograft and 17% with open debridement. This is similar to the results in the present study. Soft tissue results significantly favored the test compared to the controls in the above mentioned studies. This was not true in our results where there were no statistical differences in soft tissue furcation results with bioactive glass and open debridement. Considering that 5 of the 9 treated furcation sites in our study were lingually located may account for the difference in results. Soft and hard tissue improvements with significant advantage in the graft treated sites were seen in our intraosseous defect results. This is similar to those seen in sev- Figure 48. Preoperative osseous depih of the test site was 5.68 mm. eral comparisons studies on the use of various alloplasts versus open debridement.24-23-21-'2 All of these studies demonstrated an advantage in grafted versus open debridement sites in defect fill and gain in clinical attachment levels. The 2 exceptions showed a statistically significant advantage in fill, but not in attachment level gain.2"•" These latter studies evaluated 6-month re-entry changes. Our 12- month re-entry time and other differences in methodology may account for differences in results. The results of the present study are generally in agreement with the findings of Zamet et al. in their clinical comparison of intrabony defects treated with bioactive glass or open flap debridement.16 Their conclusion that bioactive glass treated sites showed a "greater trend to improvement" compared to open debridement treated sites is consistent with our findings. Although no means or re-entry bone measurements were reported in their study, the CADIA analysis indicated greater radiographic density and volume in bioactive glass treated sites. This, too, is consistent with the greater fill of defect documented in the present study with bioactive glass versus open debridement treated sites.16 In the present study, improvement in soft and hard tissue parameters occurred in both groups in spite of the fact that there was no significant change in plaque index or gingival index 12-months postsurgery compared to baseline values. Moreover these parameters were not significantly different in a comparison between test and control sites. The lack of improvement in home care in this university-based population must be viewed in the context of poor compliance even in private periodontal practices, where "complete compliance was seen in one third or less of the patients."33 Perhaps improved compliance could have been achieved with more time and individual effort. 708 BIOACTIVE (;i.\SS BONK (.RAH \ HUMAN PERIODONTAL LESIONS J Periodontol June 1998 If better plaque control were attained, clinical results may have been improved.14••" Although the above mentioned controlled human reentry studies show similar trends, direct comparison of clinical results and materials may lead to invalid conclusions. 1" Differences in patient population, study design, measurement techniques, microbial pathogens, disease activity, and human defect variation between populations make it difficult to compare clinical results.'^ Although several defect characteristics which may effect healing responses have been identified, control of these factors in a human clinical comparison study is impossible."1 Moreover in many of these studies, including (he present investigation, the periodontal status of the soft tissue complex as well as the probing force may result in inaccurate or inconsistent probing measurements.'"42 Hie improved clinical hard and soft tissue responses at the bioactive glass treated sites may be a function of the chemical reactivity of the material. When the material comes in contact with body fluids a unique surface reaction occurs within minutes of implantation.i: Initially there is an ionic exchange whereby the cations are leached from the surface of the material in exchange for hyrodonium or hydrogen ions forming sttanol groups (SiOH). This ion exchange process leads to an increase in interfacial pH.4' Silanol groups bond to adjacent silanol groups through a polycondensation reaction forming a silica- rich gel layer {in the particle surface. Silica plays a key role in developing the bone bonding of bioactive glasses.44 This silica-rich gel layer has a high surface area which creates a site for the redeposition of calcium and phosphorous from the material and blood.•" Within hours a calcium phosphorous layer forms on top of the silica gel layer. Initially this calcium phosphate layer is amorphous because it is thin, but in time as the layer builds up in thickness and size crystallinity is detected, it becomes a crystalline hydroxy carbon ate apatite (HCA) layer which is identical to bone mineral. This apatite layer provides the basis for the bonding of bone and the material. For a bond with tissue to occur, a layer of biologically active HCA layer must form. This surface reaction occurs until all of the ions in the internal part of the glass have undergone ionic exchange and ultimately the HCA layer becomes remodeled and incorporated into the bone. The primary advantage of bioactive glasses is their rapid rate of surface reaction which leads to fast tissue bonding.'-4* Particle sizes range from 90 to 710 microns, Smaller particles of < 300 microns undergo complete ionic dissolution and are not present by 1 year. These particles are completely devoid of any cations. The larger particle sizes are present for longer periods of time, but by 3 years the particles have been replaced by bone.J(l The silica-rich gel layer has a negatively charged surface. This increases the electrostatic charges enough so that water is absorbed quickly. Hydrogen bonding occurs between the water molecule and the hydroxyl groups of the silanol. This hydrostatic attraction gives bioactive glass a cohesiveness that when in contact with blood is prevented from migrating from the surgical site. This does not occur with HA.i:4347 The negatively charged surface of the HCA layer attracts proteins such as growth factors and fibrin which act like an "organic glue" attracting osteoblastic stem cells to the layer which differentiate into osteoblasts and produce bone. Collagen attaches to the surface and embeds into the HCA layer. Apical migration of the junctional epithelium is indirectly inhibited by the extension of the collagen up to the junctional epithelium.4* Histological differences in the repair response was seen in a study comparing bioactive glass, fluoride bioactive glass, tricalcium phosphate, and hydroxyapatite in Patus monkeys. In the bioactive glass sites no new attachment was seen at 1 month and particles were present in the defects surrounded by connective tissue. At 9 months, the bioactive glass particles were seen within the bone and the junctional epithelium was close to the original level. The other materials were slower to act and apical migration of the junctional epithelium was evident.4" The results of the present study show that bioactive glass improves the healing outcomes when probing depth reduction, osseous defect fill, and gain in clinical attachment are used as clinical parameters. However, a review of the literature has shown that synthetic graft materials to date have functioned primarily as biocompatible defect fillers.-' In order to establish the efficacy of using bioactive glass or any other bioactive alloplast. long-term controlled studies and histologic evidence of regeneration are essential prerequisites. Based on the results of the present clinical investigation further studies are warranted. Acknowledgments This study was supported by USBiomaterials. Alachua. Florida. The efforts of Paul Kubilis with his assistance in the statistical analysis of the data and Daphna R. Ariel for her technical assistance are greatly appreciated. REFERENCES 1. Froum SJ. Gomez C. Periodontal regeneration. Curr Opin Perith dontol 1993:111-128. 2. Garrelt S. Bogle G. Penodontal regeneration. Curr Opin Periodoniot 1994:1(18-177, 3. Mellonig JT, Preuett AB. Moyer MP HIV inactivution in a bone allograft. J Perindomol 1992;63:979-9S3. 4. Becker W, Becker BE. Caffesse R. 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