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Clinical Evaluation of the Effectiveness of Enamel Matrix Proteins and Autologous Bone Graft in the Treatment of Mandibular Class II Furcation Defects: A Series of 11 Patients

Mario Aimetti, MD, DDS* Furcation defects present one of the Federica Romano, DDS** greatest challenges in periodontal clin- Enrico Pigella, DDS** ical practice.1 The anatomic features of Matteo Piemontese, MD, DDS*** furcation-involved molars make peri- odontal treatment difficult and regen- erative outcomes unpredictable.2,3 These shortcomings and advances in developmental biology have caused a The purpose of this study was to evaluate the results of treatment of buccal growing interest in the possibility of mandibular Class II furcation defects with a combination of autologous bone modulating the periodontal wound- grafts and over a 24-month period. Eleven individuals healing process using biologic media- with were selected and contributed one furcation defect 4 each. Statistically significant improvements in mean vertical probing attachment tors. Enamel matrix proteins are level and horizontal probing attachment level were obtained at the 2-year evalua- secreted by cells of the Hertwig epithe- tion. Complete clinical closure was achieved in four sites, which exhibited favor- lial root sheath during root develop- able defect morphology for this regenerative procedure. All other residual defects ment and are crucial in stimulating the were reduced to Class I. (Int J Periodontics Restorative Dent 2007;27:441–447.) formation of acellular root and associated tooth-supporting tis- sues.5 The topical application of com- mercially available enamel matrix pro- teins to previously diseased roots appears to promote regenerative processes, mimicking developmental interactions in the clinical setting.6 Several studies have reported clinical and histologic evidence of the regen- *Professor and Head, Department of Biomedical Sciences and Human Oncology, Section of , University of Torino, Italy. erative potential of amelogenins in **Instructor, Department of Biomedical Sciences and Human Oncology, Section of periodontal tissues.7–9 Recently, Periodontology, University of Torino, Italy. enamel matrix proteins have been ***Associate Professor, Department of Periodontology, University Politecnica della Marche, employed in the management of Ancona, Italy. mandibular Class II furcation defects Correspondence to: Dr Mario Aimetti, Corso Marconi, 13, 10125 Torino, Italy; fax: +390- and have led to significant clinical 116682286; e-mail: [email protected].

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Fig 1 (left) Preoperative view of mandibu- lar right first molar.

Fig 2 (right) Intrasurgical view of Class II buccal furcation defect at the mandibular right first molar with a straight probe. The horizontal depth amounted to 4 mm, and the furcal bone crest was located below the interproximal bone level.

improvements.10,11 However, at pres- Method and materials logic periodontal treatment. Surgical ent, there are no data available on the treatment of the furcation defects was effects of the simultaneous use of Study design and patient not scheduled until patients presented enamel matrix derivative (EMD) and selection with full-mouth plaque and full-mouth bone grafts for the treatment of peri- bleeding scores under 20%. odontal furcation defects. The combi- Eleven patients (five women and six nation of osseous grafting with amel- men; mean age 49.64 ± 5.12 years) ogenins has the potential to result in a referred to the Department of Surgical procedures synergistic effect of both materials. Periodontology, University of Torino, Whereas the bone graft may act as an diagnosed with chronic periodontitis, All surgical procedures were performed osteogenetic, osteoconductive, and and showing at least one mandibular by a single clinician. An intrasulcular osteoinductive material while also facial Class II furcation defect were incision was made on the buccal and maintaining the defect space, amelo- recruited consecutively. These subjects lingual aspects of the experimental site genins can work at the root level, pro- were nonsmokers, free of systemic dis- and extended one or two teeth mesial moting periodontal regeneration. The ease, and receiving no medications. and distal to the treated area and inter- additional effect of the association of Only vital teeth with a minimum of 2 proximally. In this way, as much kera- enamel matrix proteins and bone graft- mm of keratinized tissue (to provide tinized tissue as possible was preserved ing material has been reported for ver- coverage of the furcation entrance dur- and no vertical releasing incisions were tical bone defects.12,13 ing surgery) were included. If suitable performed. Full-thickness buccal and Therefore, the aim of the present first and second mandibular molars lingual flaps were raised approximately investigation was to evaluate, clinically were present in the same patient, the 2 mm beyond the mucogingival junc- and radiographically, the effectiveness first molars were selected for the study. tion, giving access to the furcation. Root of the combination of amelogenins A total of 11 furcation defects were was accomplished using and autologous bone grafts for the treated with a combination of EMD ultrasonic manual instruments and car- treatment of buccal Class II furcation- (Emdogain, Straumann) and autolo- bide burs (Brasseler 7104014). The involved mandibular molars. gous bone grafts. morphology of the furcation defect was Prior to treatment, each patient examined and open surgical measure- received a description of the investi- ments were recorded (Figs 1 and 2). gation and provided written, informed Bone grafts were harvested from consent. Three months before the the maxillary tuberosity, placed into a surgery, all patients completed etio- sterile dappen dish, and mixed with

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Figs 3a and 3b Application of EMD (a, left) and autologous bone graft (b, right) on denud- Fig 4 The flap was sutured to completely ed root surface of the affected tooth. cover the coronal entrance of the furcation.

EMD. The preliminary sutures were Postsurgical infection control (PAL-H) and vertical probing attach- made with vertical mattress sutures. and maintenance care ment level (PAL-V) were recorded at Root surfaces were then conditioned the midbuccal aspect of each furcation with a 24% ethylenediaminetetraacetic Patients were placed on amoxicillin (2 site using a Williams probe and a cali- acid (EDTA) gel (pH 6.7, PrefGel, g/day) for 6 days, and nimesulide was brated Nabers probe, respectively. The Straumann) for 2 minutes, after which prescribed for pain control. They were degree of furcation involvement was the surgical area was thoroughly rinsed instructed to clean the surgical sites calculated from the PAL-H according to with sterile saline solution. EMD was using a roll technique with an ultrasoft Hamp et al.14 applied immediately, starting at the and to rinse twice daily with Probing depth (PD), clinical attach- farthest end of the involved furcation 0.12% digluconate ment level (CAL), and location of the and covering the entire denuded root (60 seconds) for 4 weeks (REC) were scored at surface (Fig 3a). Great care was taken after surgery. six sites around each experimental to control bleeding and to prevent Recall appointments were sched- tooth using a Williams periodontal contamination of the surgical area with uled weekly during the first month and probe and rounded up to the nearest the use of sterile gauzes. The graft was subsequently at 3-month intervals up 0.5 mm. To evaluate sta- packed into the defect using a con- to 2 years postsurgery. Full-mouth pro- tus and the degree of gingival inflam- denser, and EMD was reapplied to fessional tooth cleaning was per- mation, the full-mouth plaque score cover the defect site and the bone formed and oral hygiene reinforced at (FMPS) and full-mouth bleeding score graft (Fig 3b). Flaps were repositioned each appointment. (FMBS) were determined. to the cementoenamel junction and mattress sutures were applied to Intrasurgical measurements obtain primary closure (Fig 4). Measurements The following linear measurements Gentle intermittent pressure was (mm) were recorded along the mid- applied to the surgical site for 4 to 5 Clinical measurements buccal plane of each furcation site to minutes to minimize blood clot for- Subjects were clinically monitored at characterize defect morphology and mation. No periodontal dressing was baseline (1 week before surgery) and root configuration following surgical placed over the surgical area. Sutures 24 months postoperatively by the site preparation. were removed at 7 days after surgery. same calibrated examiner. The primary outcome of the study was the change 1. Distance from the cementoenamel in horizontal furcation depth. junction (CEJ) to the roof of the fur- Horizontal probing attachment level cation (CEJ-ROF)

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Fig 5 Clinical soft tissue healing at the Table 1 Distance from furcation roof to 24-month evaluation. alveolar crest, as determined surgically at included defects

Group No. % A (0 to 3 mm) 2 18.2 B (4 to 6 mm) 9 81.8 C (≥ 7 mm) 0 0

Table 2 Intrasurgical characteristics of Table 3 Radiographic characteristics of defects (in mm) defects (in mm)

Measurement Mean SD Measurement Mean SD CEJ-BC 5.91 1.32 CEJ-AC 6.08 1.36 CEJ-BD 7.68 2.00 CEJ-Fx 3.41 1.24 CEJ-ROF 3.09 1.22 FW 2.23 0.22 HOPAL 6.27 1.68 CEJ-BL 5.91 1.80 PBH 5.84 1.77 CEJ-AC = CEJ line to alveolar crest at furcation site; CEJ-Fx = CEJ to fur- cation fornix; FW = furcation width at the level of the alveolar crest; CEJ-BC = CEJ line to BC; CEJ-BD = CEJ to base of bone defect; CEJ-ROF = CEJ-BL = CEJ to interproximal bone crest. CEJ to furcation roof; HOPAL = horizontal probing attachment level at the level of alveolar crest; PBH = CEJ to interproximal bone crest.

2. Distance from the CEJ to the alveo- proximal bone height above the furcal and (5) the AC line. The following lin- lar bone crest (CEJ-BC) bone crest were assigned a positive ear measurements were recorded by 3. Distance from the CEJ to the base score. the same examiner: of bone defect (CEJ-BD) 4. Distance from the alveolar bone Radiographic measurements 1. CEJ-AC line: distance from the CEJ crest to the base of the defect A commercially available film holder line to the AC within the furcation (BC-BD) device (Rinn centering device, perpendicular to the CEJ line and 5. Distance from the furcation roof to Dentsply) with personalized Duralay through Fx the coronal alveolar bone crest bite blocks was employed to obtain 2. Fx-AC line: distance from the AC (ROF-BC) standardized radiographs of all teeth line to Fx, perpendicular to the AC 6. Horizontal probing attachment level included in the study at baseline and line at the alveolar bone crest (HOPAL) at 24 months postsurgery. Digital 3. CEJ-Fx: difference between CEJ- manipulation and measurement of lin- AC line and Fx-AC line The distance from the CEJ to the ear distances were performed using 4. Furcation width (FW): distance mesial and distal alveolar bone crest Archimed implant software.15 The fol- between the mesial and distal root (PBH) was related to the CEJ-BC of lowing landmarks were identified on the level of the AC within the the respective furcation and scored as according to Horwitz et al16: (1) the furcation a dichotomous variable. Furcation CEJ, (2) the alveolar crest (AC), (3) the 5. CEJ-BL: distance from the CEJ to defects with mesial and/or distal inter- furcation fornix (Fx), (4) the CEJ line, the mesial and distal bone crest.

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Statistical analysis Table 4 Changes in clinical and radiographic parameters (mean ± SD) during the 2-year observation period All six scores recorded around each experimental tooth were used for sta- Measurement Baseline 24 mo Change P tistical analysis of PD, CAL, and REC. PD 4.26 ± 1.73 2.59 ± 0.98 1.67 ± 1.37 < .0001 Radiographic bone gain/loss, PAL-H, CAL 5.73 ± 2.62 3.51 ± 1.54 2.23 ± 1.92 < .0001 REC 1.48 ± 1.39 0.92 ± 1.10 0.56 ± 0.99 < .0001 and PAL-V were measured at furcation PAL-H 4.91 ± 0.83 1.55 ± 1.29 3.39 ± 1.12 < .0001 sites. The data were expressed as PAL-V 6.64 ± 2.20 3.00 ± 0.89 3.64 ± 2.11 < .0001 means ± standard deviations. The CEJ-AC 6.08 ± 1.36 5.48 ± 1.25 0.60 ± 0.30 < .0001 paired t test was used to compare clin- PD = probing depth; CAL = clinical attachment level; REC = recession depth; PAL-H = horizontal probing attachment level; PAL-V = vertical probing attachment level; CEJ-AC = CEJ line to alveo- ical and radiographic measurements lar crest at furcation site. between baseline and at the 2-year evaluation. For FMPS and FMBS val- ues, a Chi-square analysis was per- formed. All results were considered to be significant at the .05 level.

Results

All patients completed the 2-year fol- low-up period. No infections, delayed healing, or adverse tissue reactions were observed during the course of the study (Fig 5). One patient (9.1%) Figs 6a and 6b Defect during reentry procedure 2 years after surgery. (a, left) A paramar- ginal incision was made at the furcation area. (b, right) The furcation closure was assessed experienced root hypersensitivity dur- with a Williams . Newly formed tissue completely covered the furcation ing the early healing period. FMPS and defect. The new tissue appeared bonelike and resisted penetration. FMBS remained under 20% during the entire study period. The morphologic and radio- graphic characteristics of the included defects are reported in Tables 1 to 3. Four molars (36.36%) presented with a short root trunk (CEJ-ROF of 2 mm), involvement, subclass A (0 to 3 mm) treatment effect was observed in terms two sites (18.18%) had a CEJ-ROF of represented 18.2% of defects, and of clinical and radiographic gains (P < 3 mm, and the remaining five sites subclass B (4 to 6 mm) represented .0001). Complete furcation closure was (46.46%) presented with a long CEJ- 81.8% of the furcations.17 In addition, obtained in four defects (36.36%). At ROF (4 to 5 mm). The mean FW was six teeth (54.54%) exhibited interprox- the 2-year examination, one furcation 2.23 ± 0.22 mm. Four defects (36.36%) imal bone height coronal to the mid- defect among those exhibiting com- were early furcation sites (PAL-H (≤ 4 furcal bone level. plete clinical closure was reentered. mm), whereas seven (64.64%) were The clinical and radiographic Newly formed hard tissue completely advanced lesions (PAL-H (≥ 5 mm). results obtained in the study are sum- covered the defect (Fig 6). All seven According to the subclassification of marized in Table 4. At the 24-month sites with residual furcation involve- the vertical component of the furcation examination, a statistically significant ment had improved to Class I.

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thorough root preparation by means of fluted carbide burs and Gracey curettes. As previously demonstrated by Dibart et al, rotating instruments would seem to be more effective than hand scaling in achieving decontami- nation of furcation areas.21 At present there are no data avail- able from other studies on the effects Figs 7a and 7b Preoperative (a, left) and 24-month postoperative (b, right) radiographs of the mandibular right first molar are suggestive of new bone formation and increased bone of EMD and autologous bone graft density. application in furcation defects. A few investigations have addressed the clin- ical effectiveness of amelogenins in An increase in radiopacity was defects exhibited interproximal bone the management of Class II furcated detected in 54.54% of the furcation height coronal to the furcal bone crest, molars.10,11 They reported frequencies defects (Fig 7). 64.64% had advanced horizontal of complete closure that varied from attachment loss, 81.82% were subclass 0% to 18% and gains in PAL-H that B defects, and 36.36% presented a ranged from 0.8 mm to 2.6 mm.10,11 Discussion short root trunk. Molars with short root The additional effect of the com- trunks are considered less favorable bination of enamel matrix proteins and The results of the present study indi- for membrane coverage, whereas the material has been cate that a combination of EMD and root trunk length would not seem to demonstrated in vertical bone autologous bone graft may be effica- impair the outcome of EMD therapy.20 defects.12,13 The application of autol- cious in improving the clinical furcation We noted a strict correlation between ogous bone graft as an adjunct to status of mandibular molars. At the baseline proximal bone height and amelogenins provides, in addition to 24-month evaluation, 4 of 11 Class II gains in vertical and horizontal attach- its osteogenetic, osteoconductive, and furcation–involved molars (36.36%) dis- ment levels. Four of the six defects osteoinductive properties, an advan- played complete closure, while the with furcal bone height below the adja- tage of space maintenance. By filling remaining 7 defects (63.64%) had cent hard tissues displayed complete the defect it enhances the stability of improved to Class I. This is clinically rel- furcation closure at the 2-year evalua- the grafting material and provides bet- evant, because Class I furcation defects tion. The residual defects, which pre- ter material handling characteristics are generally considered maintainable sented an interproximal bone level at than EMD alone. It has been sug- with nonsurgical therapy and effective or below furcal bone crest, were less gested that the absorption of EMD in plaque control. responsive to the combined therapy bone graft particles may increase Several factors were found to be and improved only to Class I. retention rates of EMD for a sufficient predictive of regenerative treatment The architecture of the furcation amount of time and enhance thera- outcome. Apart from the level of entrance represents another signifi- peutic outcomes.9 plaque control and smoking habits, cant determinant of treatment success. In the present investigation we bony defect morphology, anatomy of A narrow opening, which is associated avoided reentry procedures.10 With the roots, radicular trunk length, and with a greater amount of regenera- the 24-month stability in clinical and interproximal bone height relative to tion, may be an obstacle to effective radiographic outcomes, coupled with the furcal bone crest have been related and plaque removal.18 All fur- the additional discomfort for the to regenerative outcomes.18,19 In the cations treated in this study exhibited patient of a reentry surgery and a pos- current investigation, 54.54% of sufficient root divergency to permit sible traumatic effect on newly formed

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tissues, a routine second intervention 6. Giannobile WV, Somerman MJ. Growth 15. Aimetti M, Romano F, Pigella E, Pranzini F, was not ethically justified. For this rea- and amelogenin-like factors in periodon- Debernardi C. Treatment of wide, shallow, tal wound healing. A systematic review. and predominantly 1-wall intrabony son, only one defect was reentered at Ann Periodontol 2003;8:193–204. defects with a bioabsorbable membrane: 24 months. In this case, complete fill of 7. Cochran DL, King GN, Schoolfield J, A randomized controlled clinical trial. J the furcation by newly formed hard tis- Velasquez-Plata D, Mellonig JT, Jones A. Periodontol 2005;76:1354–1361. sue was evident. The effect of enamel matrix proteins on 16. Horwitz J, Matchei EE, Reitmeir P, Holle R, A limitation of this clinical investi- periodontal regeneration as determined Kim TS, Eickholz P. Radiographic parame- by histological analyses. J Periodontol ters as prognostic indicators for healing of gation was the inability to assess the 2003;74:1043–1055. Class II furcation defects. J Clin Periodontol histologic characteristics of the newly 8. Donos N, Sculean A, Glavind L, Reich E, 2004;31:105–111. formed tissue. However, new attach- Karring T. Wound healing of degree III fur- 17. Tarnow D, Fletcher P. Classification of the ment formation has been demon- cation involvements following guided tis- vertical component of furcation involve- strated histologically in Class III furca- sue regeneration and /or Emdogain. A his- ment. J Periodontol 1984;55:283–284. tologic study. J Clin Periodontol tion involvements8,22 treated with 18. Bowers GM, Schallorm RG, McClain PK, 2003;30:1061–1068. amelogenins and in intrabony defects Morrison GM, Morgan R, Reynolds MA. 9. Kalpidis CDR, Ruben MP. Treatment of Factors influencing the outcome of regen- treated with enamel matrix proteins intrabony periodontal defects with enam- erative therapy in mandibular class II fur- and autologous bone graft.13 el matrix derivative: A literature review. J cations: Part I. J Periodontol 2003;74: Periodontol 2002;73:1360–1376. 1255–1268. 10. Donos N, Glavind L, Karring T, Sculean A. 19. Roussa E. Anatomic characteristics of the References Clinical evaluation of an enamel matrix furcation and root surfaces of molar teeth derivative in the treatment of mandibular and their significance in the clinical man- degree II furcation involvement: A 36- agement of marginal periodontitis. Clin 1. Jepsen S, Eberhard J, Herrera D, month case series. Int J Periodontics Anat 1998;11:177–186. Needleman I. A systematic review of guided Restorative Dent 2003;23:507–512. tissue regeneration for periodontal furca- 20. Hutchens LHJ. Hypothetical considera- tion defects. What is the effect of guided 11. Jepsen S, Heinz B, Jepsen K, et al. A ran- tions in the regenerative treatment of tissue regeneration compared with surgi- domized clinical trial comparing enamel molar furcation defects. Curr Opin cal debridement in the treatment of furca- matrix derivative and membrane treatment Periodontol 1996;3:157–167. tion defects? J Clin Periodontol 2002; of buccal Class II furcation involvement in 21. Dibart S, Capri D, Casavecchia P, Nunn M, 29:103–116. mandibular molars. Part I: Study design Skobe Z. Comparison of the effectiveness and results for primary outcomes. J of in vivo using 2. Camelo MC, Nevins ML, Nevins M. Periodontol 2004;75:1150–1160. Treatment of Class II furcations with auto- hand vs. rotary instruments. Int J genous bone graft and e-PTFE mem- 12. Zucchelli G, Amore C, Montebugnoli L, Periodontics Restorative Dent 2004;24: branes. Int J Periodontics Restorative Dent De Sanctis M. Enamel matrix proteins and 370–377. 2000;20:233–243. bovine porous bone mineral in the treat- 22. Hovey LR, Jones AA, McGuire M, Mellonig ment of intrabony defects: A comparative 3. Reynolds MA, Aichelmann-Reidy ME, JT, Schoolfield J, Cochran DL. Application controlled clinical study. J Periodontol of periodontal tissue engineering using Branch-Mays GL, Gunsolley JC. The effi- 2003;74:1725–1735. cacy of bone replacement graft in the treat- enamel matrix derivative and a human ment of periodontal osseous defects. A 13. Cochran DL, Jones A, Heijl L, Mellonig JT, fibroblast-derived dermal substitute to systematic review. Ann Periodontol Schoolfield J, King GN. Periodontal regen- stimulate periodontal wound healing in 2003;8:227–265. eration with a combination of enamel Class III furcation defects. J Periodontol matrix proteins and autogenous bone 2006;77:790–799. 4. Camelo M, Nevins ML, Schenk RK, Lynch grafting. J Periodontol 2003;74: SE, Nevins M. Periodontal regeneration in 1269–1281. human Class II furcation using purified recombinant human platelet-derived 14. Hamp SE, Nyman S, Lindhe J. Periodontal growth factor-BB (rhPDGF-BB) with bone treatment of multirooted teeth. Results allograft. Int J Periodontics Restorative after 5 years. J Clin Periodontol 1975;2: Dent 2003;23:213–225. 126–135. 5. Hammarström L. Enamel matrix, cemen- tum development and regeneration. J Clin Periodontol 1997;24:658–668.

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