Clinical Outcomes of Socket Preservation Using Bovine-Derived

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Clinical Outcomes of Socket Preservation Using Bovine-Derived Xenograft Collagen and Collagen Membrane Post–Tooth Extraction: A 6-Month Randomized Controlled Clinical Trial

Vincenzo Iorio-Siciliano, DDS, PhD1 Several studies have demonstrated Andrea Blasi, DDS, PhD1 that alveolar bone structures are lost Michele Nicolò, MD, DDS2 following tooth extraction.1–3 Dur- Alessandro Iorio-Siciliano, DDS3 ing the physiologic healing process, 2 Francesco Riccitiello, MD, DDS the bone loss will result in a ridge re- 3 Luca Ramaglia, MD, DDS duced in both vertical and horizontal dimensions.4 These physiologic alve- The aim of this study was to evaluate the clinical remodeling of the alveolar olar socket changes may limit bone socket following the application of bovine-derived xenograft collagen and availability, affecting conditions for collagen membrane compared to natural spontaneous healing during the ideal implant placement. For this rea- first 6 months following tooth extraction. A total of 20 patients with 20 fresh son, various bone grafts are used to alveolar sockets were randomly allocated into a test or control group. After a 6-month follow-up period, surgical reentry was performed and implants preserve the alveolar ridge following were placed. Significant statistical differences were recorded in terms of tooth extraction.5,6 Varying degrees vertical and horizontal bone changes between the test and control groups. of success have been reported in Within the limitations of this study, socket preservation procedures may maintaining the anatomical dimen- provide more favorable conditions for subsequent implant placement. Int J sions of the alveolar ridge after tooth Periodontics Restorative Dent 2017;37:e290–e296. doi: 10.11607/prd.2474 extraction.7–9 However, a recent systematic review10 suggested that socket preservation techniques may not prevent physiologic resorptive bone processes after tooth extraction but may reduce the resultant dimensional change to the bone. Vignoletti et al11 evaluated the scientific evidence on the efficacy of the surgical protocols designed to preserve the alveolar ridge after tooth removal. Results of meta-analyses showed statisti- 1Adjunct Professor, Department of Neurosciences, Reproductive and Odontostomatological cally significantly smaller variations Sciences, Department of Periodontology, University of Naples Federico II, Naples, Italy. 2Associate Professor, Department of Neurosciences, Reproductive and in bone height (1.47 mm) and width Odontostomatological Sciences, Department of Periodontology, University of Naples (1.83 mm) for grafted sites compared Federico II, Naples, Italy. to nongrafted sites. The potential 3Private Practice, Pomigliano d’Arco, Italy. benefit of socket preservation pro- Correspondence to: Dr Vincenzo Iorio-Siciliano, Department of Neurosciences, cedures has been demonstrated to Reproductive and Odontostomatological Sciences, Department of Periodontology, result in significantly less vertical and University of Naples Federico II, Naples, Italy. horizontal contraction of the alveolar Fax: +390818845462. Email: [email protected] bone crest.12 In recent experimental ©2017 by Quintessence Publishing Co Inc. studies,13,14 the placement of bovine-

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© 2017 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER. e291 derived xenograft collagen into fresh extraction sockets appeared to preserve the dimension of the alveolar ridge and thereby counteract the marginal ridge contraction that oc- curs after tooth removal. The aim of the present study was to evaluate the clinical changes in fresh alveolar sockets treated with bovine-derived xenograft collagen and collagen membrane compared Fig 1 Occlusal view of fractured second Fig 2 Occlusal view of extraction socket. with spontaneous healing during a premolar. 6-month follow-up period. or control (ie, spontaneous healing). baseline; and presence of at least 2 The study protocol was submit- mm of keratinized tissue to allow flap Materials and Methods ted to and approved by the Ethical management. Subjects were exclud- Committee of the “Federico II” Uni- ed on the basis of the presence of Experimental Design versity, Naples, Italy (protocol No. any medical condition contraindicat- 25/14). Prior written consent was ob- ing surgical intervention, pregnancy The study was designed as a ran- tained, and the study was conduct- or lactation, or tobacco smoking. domized controlled clinical trial. In ed according to the principles of the the test sites, bovine-derived xeno- Declaration of Helsinki on experi- graft with 10% collagen (Bio-Oss, mentation involving human subjects. Experimental Procedures Geistlich) was placed immediately This report was conducted accord- after tooth extraction and covered ing to the CONSORT statement for Clinical Parameters with collagen membrane (Bio-Gide, improving the quality of reports of To achieve a baseline, FMPS15 and Geistlich), while in the control sites parallel-group randomized trials. FMBS16 were recorded at six sites regenerative procedures were not per tooth (distobuccal, buccal, me- performed. A single fresh alveolar siobuccal, mesiolingual, lingual, and socket was treated in each subject. Patient Population distolingual) using a manual peri- Each patient was unaware of which odontal probe (PCP-UNC 15, Hu- procedure had been performed. A total of 20 fresh alveolar sockets Friedy) and a probing force of 0.3 N. The fresh alveolar sockets were ran- in 20 patients were selected. The domly assigned to the test or control subjects were recruited from the Surgical Procedures group with the allocation conducted patient pool of the Department of After the elevation of the muco- using a commercially available com- Periodontology, “Federico II” Uni- periosteal flap extending one tooth puter software package (NCSS- versity, Naples, Italy. The following in the mesial and distal directions, PASS, Number Cruncher Statistical inclusion criteria were applied: aged tooth extraction was performed Systems). Treatment allocation was ≥ 18 years; presence of mandibular using forceps after a slight luxation performed at the time of surgery, or maxillary teeth to be extracted operated with rounded blades, so after tooth extraction, by opening because of an endodontic failure, that the periodontal socket fibers an envelope containing the informa- caries, or root fracture; integrity of were cut. Multirooted teeth were tion that the procedure was test (ie, extraction socket walls; Full-Mouth carefully extracted after separation bovine-derived xenograft with 10% Plaque Score (FMPS) and Full-Mouth of the roots (Figs 1 and 2). Granula- collagen and collagen membrane) Bleeding Score (FMBS) ≤ 25% at tion tissue was removed with hand

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Fig 3 Fresh alveolar socket filled with Fig 4 Bovine-derived xenograft with 10% Fig 5 The suture left the collagen bovine-derived xenograft with 10% collagen covered by collagen membrane. membrane partially uncovered. collagen.

Fig 6 Vertical distance from reference Fig 7 Horizontal alveolar width (WIDTH). Fig 8 Thickness of buccal alveolar bone periodontal probe that connected the wall. cementoenamel junction of the adjacent teeth (CEJ) and the alveolar crest (AC). instruments, and the fresh alveolar it (Fig 5). For the control group, no The thickness was measured at the socket was rinsed with sterile saline. further treatment was applied, and center of the buccal and lingual Subjects were randomly assigned to the coagulum in the socket was left walls, 1 mm apically from the crest. the test (n = 10) or control (n = 10) open for spontaneous healing. Horizontal alveolar width and thick- group according to randomized ness of the alveolar walls were mea- procedures. For the test group, Intrasurgical Measurements sured using a manual caliper. bovine-derived xenograft with 10% After tooth extraction and before collagen (Bio-Oss, Geistlich) was randomization procedures, the fol- Postsurgical Instructions and placed into fresh alveolar sock- lowing intrasurgical measurements Infection Control ets, completely filling the socket were recorded: vertical distance For both groups, the sutures were but without applying compression from reference periodontal probe removed after 7 days. Patients re- (Fig 3), and covered with a colla- that connected the cementoenamel ceived ibuprofen (600 mg immedi- gen membrane (Bio-Gide, Geistlich) junction (CEJ) of the adjacent teeth ately after the surgical intervention (Fig 4). The collagen membrane was and alveolar crest (AC) (Fig 6), hori- and again after 4 hours) and system- left intentionally exposed to the oral zontal alveolar width (WIDTH) (Fig ic antibiotics (amoxicillin + clavulanic cavity, and nonresorbable monofila- 7), and thickness of the buccal and acid, 1 g twice per day for 7 days). ment sutures were used to stabilize lingual alveolar bone walls (Fig 8). Patients were instructed to rinse

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Surgical Reentry After 6 months of healing, a surgical reentry procedure was performed (Fig 9). The full-thickness flap was elevated to allow access to the bone crest. The vertical and horizontal measurements (CEJ-AC and WIDTH) were repeated. All pa- Fig 9 Occlusal view of soft tissues healed Fig 10 Occlusal view of hard tissues tients received a submerged dental after 6 months of follow-up. healed and implant placement after 6 months of healing. implant (Fig 10). The surgical flaps were subsequently sutured.

Statistical Analysis Table 1 Patient Population

Test sites Control sites P Descriptive statistical analyses (mean ± SD) were used to represent Age (y) 38.2 ± 9.4 40.2 ± 12.1 .73* the patient population. All variables Sex (M/F) (%) 60/40 50/50 .66* were expressed in millimeters with Mean FMPS (%) 21.2 ± 2.6 19.7 ± 3.3 .21* the exception of FMPS, FMBS, and Mean FMBS (%) 17.1 ± 3.1 16.7 ± 3.7 .85* sex, which were expressed as per- Anterior/Posterior (n) 2/8 1/9 1.00* centages. Since the variables were *Not statistically significant. not normally distributed, nonpara- FMPS = Full-Mouth Plaque Score; FMBS = Full-Mouth Bleeding Score. metric testing was performed. To compare subjects in the test and who fulfilled the inclusion criteria cally significant difference P( > .05) control groups (intergroup compari- were enrolled. No statistically sig- recorded in the test group (0.3 ± son), Kruskal-Wallis test was chosen; nificant differences P( < .05) were 0.5 mm) with respect to the control to compare baseline and follow-up observed with respect to mean age, group (1.1 ± 1.0 mm). Table 3 illus- values (intragroup comparison), sex, FMPS, and FMBS. Table 2 sum- trates the mean change in horizontal Wilcoxon test was applied. P < .5 marizes the mean change in vertical distance (WIDTH) at buccal-palatal was accepted to identify a statisti- distance (CEJ-BC) at baseline and aspects. Statistically significant dif- cally significant difference. The data after surgical reentry between test ferences (P > .05) in WIDTH variation analysis was performed using statis- and control groups. In the test at baseline and after surgical reentry tical software (NCSS-PASS, Number group, no statistically significant dif- were noted in the test and control Cruncher Statistical System). ference (P > .05) was recorded in groups. The differences in WIDTH CEJ-BD between baseline and re- change between test and control entry. In the control group, statisti- groups were statistically significant Results cally significant differences P( < .05) (P > .05). Table 4 shows the vertical were observed at buccal and linguo- bone resorption (at the buccal as- The characteristics of the patient palatal aspects after surgical reen- pect) and horizontal alveolar bone population at baseline are present- try. Also after surgical reentry only resorption in fresh alveolar sockets ed in Table 1. A total of 20 patients at the buccal aspect was a statisti- between groups with respect to the

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Table 2 Vertical Changes (in mm; mean ± SD) Assessed at Four Sites per Alveolar Socket Between Baseline and Surgical Reentry at 6 Months

Test sites Control sites P CEJ-AC MBD LP MBD LP MBD LP Baseline 2.3 ± 0.5 2.7 ± 0.7 2.2 ± 0.6 2.4 ± 0.5 2.7 ± 0.5 3.0 ± 0.5 2.7 ± 0.5 2.8 ± 0.4 .08 .23 .07 .08 Reentry 2.3 ± 0.5 3.0 ± 0.7 2.3 ± 0.7 2.5 ± 0.5 2.7 ± 0.5 4.1 ± 1.0 2.8 ± 0.4 3.5 ± 0.7 .08 .01* .07 .003* Difference 0.0 ± 0.0 0.3 ± 0.5 0.1 ± 0.3 0.1 ± 0.3 0.0 ± 0.0 1.1 ± 1.0 0.1 ± 0.3 0.7 ± 0.7 1.00 .04* 1.00 .02 P 1.00 .08 .32 .32 1.00 .02* .32 .02* *Statistically significant. CEJ-AC = vertical distance from reference periodontal probe that connected the CEJ of the adjacent teeth (CEJ) and alveolar crest (AC); M = mesial; B = buccal; D = distal; LP = linguopalatal.

significant differences between test Table 3 Horizontal Changes (in mm; mean ± SD) Between Baseline and control groups (P < .05) were and Surgical Reentry After 6-Month Healing Period recorded in vertical and horizontal WIDTH Test sites Control sites P changes of the alveolar crest at sites Baseline 11.3 ± 2.0 12.6 ± 1.3 .11 with an initial buccal wall thickness Reentry 9.7 ± 2.3 9.8 ± 1.5 .82 > 1 mm. Difference 1.6 ± 1.3 2.8 ± 1.1 .04* P .02* .005* *Statistically significant. Discussion WIDTH = horizontal alveolar width. The findings of this randomized controlled clinical trial demonstrate that Table 4 Vertical and Horizontal Changes (in mm; mean ± SD) in the use of bovine-derived xenograft Fresh Alveolar Sockets with Respect to the with 10% collagen and collagen Thickness of the Alveolar Bone Walls membrane could preserve the hard Vertical changes Horizontal tissue dimension more successfully Buccal aspect Linguopalatal aspect changes than simply allowing spontaneous Thickness < 1 mm healing. Test sites (n = 6) 0.3 ± 0.5 0.2 ± 0.4 2.2 ± 1.3 In the current study, vertical Control sites (n = 3) 1.7 ± 0.6 1.3 ± 0.6 3.3 ± 0.6 and horizontal bone resorption at the test sites (0.3 ± 0.5 mm and P .04* .02* .03* 1.6 ± 1.3 mm, respectively) was Thickness > 1 mm lower compared with the alveolar Test sites (n = 4) 0.3 ± 0.5 0.0 ± 0.0 0.8 ± 1.0 bone resorption recorded in the Control sites (n = 7) 0.9 ± 1.1 0.4 ± 0.5 2.6 ± 1.3 control group (1.1 ± 1.0 mm and P .34 .33 .55 2.8 ± 1.1 mm, respectively). These *Statistically significant. results corroborate and expand current available evidence on the use thickness of the buccal bone wall observed in the vertical and hori- of biomaterials to promote bone (< 1 mm vs > 1 mm). Statistically zontal changes of the alveolar crest modeling and compensate marginal significant differences between test at sites with an initial buccal wall ridge resorption after tooth extrac- and control groups (P > .05) were thickness < 1 mm. No statistically tion. The present outcomes are in

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© 2017 BY QUINTESSENCE PUBLISHING CO, INC. PRINTING OF THIS DOCUMENT IS RESTRICTED TO PERSONAL USE ONLY. NO PART MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM WITHOUT WRITTEN PERMISSION FROM THE PUBLISHER. e295 agreement with findings from ex- results of the present randomized Acknowledgments perimental studies indicating that controlled trial are in agreement the use of bovine-derived xeno- with previous studies22 that record- The authors reported no conflicts of interest graft with 10% collagen may modify ed a more pronounced buccal bone related to this study. the marginal ridge resorption after resorption of grafted sites with re- tooth extraction.17 The histometric spect to nongrafted sites in case of measurements reveal that the non- thin buccal bone walls. References grafted sites (35 ± 15%) showed less A significant difference be- resorption compared to the grafted tween grafted and nongrafted sites . 1 Cardaropoli G, Araújo M, Lindhe J. sites (12 ± 10%). In the grafted sites, was noted in terms of vertical (0.3 ± Dynamics of bone tissue formation in tooth extraction sites. An experimatal the collagen membranes were ex- 0.5 mm vs 1.7 ± 0.6 mm) and hori- study in dogs. J Clin Periodontol 2003;30: posed at the time of flap suturing; zontal (2.2 ± 1.3 mm vs 3.3 ± 0.6 mm) 809–818. 2. Schropp L, Wenzel A, Kostopoulos L, however, no postsurgical wound bone resorption. Karring T. Bone healing and soft tissue healing complications were ob- Flap elevation may represent a contour changes following single-tooth served. Although studies have sug- limitation of the present study, but extraction: A clinical and radiographic 12-month prospective study. Int J Peri- gested that wound dehiscence and this surgical approach was chosen odontics Restorative Dent 2003;23: membrane exposure could result in to perform the required intrasurgi- 313–323. 3. Araújo M, Lindhe J. Dimensional ridge infection and lack of bone forma- cal measurements and to place the alterations following tooth extraction. tion,18 more recent studies show membrane. The elevation of a flap is An experimental study in the dog. J Clin that intentional exposure of bioab- generally associated with increased Periodontol 2005;32:212–218. 4. Discepoli N, Vignoletti F, Laino L, de sorbable membrane does not ad- bone resorption, and in clinical Sanctis M, Muñoz F, Sanz M. Early heal- versely affect bone regeneration practice it should be limited to the ing of the alveolar process after tooth 23 extraction: An experimental study in procedures when used to treat fresh treatment of dehiscences. the beagle dog. J Clin Periodontol 2013; extraction sockets.19,20 While the clinical relevance of 40:638–644. After surgical reentry, nongraft- socket preservation is still debated 5. Carmagnola D, Adriaens P, Berglundh T. Healing of human extraction sockets ed sites with an initial buccal bone in the literature, as is the identifica- filled with Bio-Oss. Clin Oral Implants wall of < 1 mm showed a tendency tion of the best surgical technique Res 2003;14:137–143. 6. Nevins M, Camelo M, De Paoli S, et al. to present more resorption with re- and grafting materials/membranes, A study of the fate of the buccal wall spect to grafted sites, which nega- the present study defines a clear of the extraction sockets of teeth with tively interferes with rehabilitation. need for postextractive socket prominent roots. Int J Periodontics Re- storative Dent 2006;26:19–29. In addition, no significant difference preservation in case of thin alveolar 7. Iasella JM, Greenwell H, Miller RL, et al. was noted between grafted and walls. Ridge preservation with freeze-dried bone allograft and a collagen mem- nongrafted sites with buccal bone brane compared to extraction alone for wall > 1 mm. These findings demon- implant site development: A clinical and strate that if buccal bone thickness Conclusions histologic study in humans. J Periodon- tol 2003;74:990–999. is sufficient (ie, > 1 mm), mainte- 8. Crespi R, Capparè P, Gherlone E. Den- nance of the bone dimension is pos- Although vertical and horizontal tal implants placed in extraction sites grafted with different bone substitutes: sible without socket preservation. bone resorption occurred indepen- Radiographic evaluation at 24 months. However, this kind of situation is un- dently of the use of bovine-derived J Periodontol 2009;80:1616–1621. fortunately rare around the maxillary xenograft collagen and collagen 9. Barone A, Todisco M, Ludovichetti M, et al. A prospective, randomized, con- anterior teeth. These findings are membrane in thicker buccal bone trolled, multicenter evaluation of extrac- supported by evidence that shows walls, it is clear that socket preservation socket preservation comparing two bovine xenografts: Clinical and histo- significant vertical and horizontal tion procedures should be recom- logic outcomes. Int J Periodontics Re- buccal bone resorption associated mended in the case of thin buccal storative Dent 2013;33:795–802. with a thin-wall phenotype.21 The bone walls.

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10. Ten Heggeler JM, Slot DE, Van der Wei- 15. O’Leary TJ, Drake RB, Naylor JE. The 21. Brownfield LA, Weltman RL. Ridge pres- jden GA. Effect of socket preservation plaque control record. J Periodontol ervation with or without an osteoinduc- therapies following tooth extraction in 1972;43:38. tive allograft: A clinical, radiographic, non-molar regions in humans: A system- 16. Claffey N, Nylund K, Kiger R, Garrett S, micro-computed tomography, and his- atic review. Clin Oral Implants Res 2011; Egelberg J. Diagnostic predictability of tologic study evaluating dimensional 22:779–788. scores of plaque, bleeding, suppuration changes and new formation of the alveo- 11. Vignoletti F, Matesanz P, Rodrigo D, and probing depth for probing attach- lar ridge. J Periodontol 2012;83:581–589. Figuero E, Martin C, Sanz M. Surgical ment loss. 3 1/2 years of observation fol- 22. Cardaropoli D, Tamagnone L, Roffredo protocols for ridge preservation after lowing initial periodontal therapy. J Clin A, Gaveglio L. Relationship between tooth extraction. A systematic review. Periodontol 1990;17:108–114. the buccal bone plate thickness and Clin Oral Implants Res 2012;23(suppl): 17. Araújo MG, Lindhe J. Ridge preserva- the healing of postextraction sockets s22–s38. tion with the use of Bio-Oss collagen: with/without ridge preservation. Int J 12. Fiorellini JP, Howell TH, Cochran D, et A 6-month study in the dog. Clin Oral Periodontics Restorative Dent 2014;34: al. Randomized study evaluating re- Implants Res 2009;20:433–440. 211–217. combinant human bone morphogenetic 18. Verardi S, Simion M. Management of 23. Barone A, Toti P, Piattelli A, Iezzi G, Der- protein-2 for extraction socket augmen- the exposure of e-PTFE membranes chi G, Covani U. Extraction socket heal- tation. J Periodontol 2005;76:605–613. in guided bone regeneration. Pract ing in humans after ridge preservation 13. Araújo M, Linder E, Wennström J, Lind- Proced Aesthet Dent 2007;19:111–117. techniques: Comparison between flap- he J. The influence of Bio-Oss collagen 19. Barone A, Ricci M, Tonelli P, Santini S, less and flapped procedures in a ran- on healing of an extraction socket: An Covani U. Tissue changes of extraction domized clinical trial. J Periodontol 2014; experimental study in the dog. Int J sockets in humans: A comparison of 85:14 –23. Periodontics Restorative Dent 2008;28: spontaneous healing vs. ridge preserva- 123–135. tion with secondary soft tissue healing. 14. Araújo MG, Liljenberg B, Lindhe J. Clin Oral Implants Res 2013;24:1231–1237. Dynamics of Bio-Oss collagen incorpo- 20. Cardaropoli D, Cardaropoli G. Preser- ration in fresh extraction wounds: An vation of the post-extraction alveolar experimental study in the dog. Clin Oral ridge: A clinical and histologic study. Implants Res 2010;21:55–64. Int J Periodontics Restorative Dent 2008;28:469–477.

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