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    AAP

    November/December 2011, Volume 32, Issue 5
    Published by AEGIS Communications


    Advances in Regeneration: Restoratively Driven, Periodontally Enhanced

    Pamela K. McClain, DDS

    Although periodontal diseases continue to be a major health concern, oral healthcare practitioners have more treatment options available today than ever before. One of the challenges in treating patients is determining which therapeutic modality will be most effective. Regenerative therapy has become more predictable clinically with histologic proof of principle evidence of regeneration. Although periodontal regeneration has become a reality for selective osseous defects, in many cases teeth are extracted in favor of dental implants.

    The mission of dentistry is to help patients establish and maintain the stomatognathic system in an optimal state of health, function, comfort, and esthetics throughout their life-span. Numerous factors impact the decision-making criteria for maintaining or extracting a tooth that has periodontal involvement. Several of the more important criteria include the restorability of the tooth, endodontic status, degree of periodontal involvement, esthetic impact, occlusion, anatomic considerations, financial impact, and medical status of the patient.

    Periodontal regeneration is the formation of new bone, cementum, and functional periodontal ligament on a previously diseased root surface.1 Numerous studies have provided proof of principle demonstrating histologic evidence of regeneration using a variety of materials/techniques in intrabony defects.2-7 In addition, there is evidence for histologic regeneration in furcation and recession defects.8-10 Once histologic evidence has been established, clinical criteria are used to validate the effectiveness/predictability of the approach. These criteria include evidence of new bone via radiographs (Figure 1 and Figure 2), bone sounding and reentry procedures (Figure 3 and Figure 4), and improvement in clinical probing attachment levels (Figure 5 and Figure 6). Diagnostic accuracy of predicting the presence of bone approaches 100% when radiographic and attachment levels are in agreement and when compared to surgical reentry data.11

    Although they are an important diagnostic tool, radiographs can be misleading in evaluating bone improvement depending upon the type of bone graft. When a mineralized bone graft is used, there is the appearance of instant radiographic defect fill (Figure 7 and Figure 8). However, regeneration has not yet occurred. In contrast, when a demineralized graft is used (such as demineralized freeze dried bone allograft), improvement is not observed radiographically until the graft has become mineralized or turned over by the body, indicating new bone formation (Figure 9, Figure 10 and Figure 11).

    The different techniques and materials currently used for periodontal regeneration include bone replacement grafts, guided tissue regeneration, biologics, and combination therapies. Bone replacement grafts are among the oldest materials used for periodontal regeneration. A meta analysis with a systematic review of demineralized freeze dried bone allograft (DFDBA) studies showed an average of 60% bone fill and consistently superior improvements in clinical parameters (clinical probing attachment levels, recession, probing depth) compared to open flap debridement in intrabony defects.12 A similar review of the use of barriers for guided tissue regeneration (GTR) showed that GTR was favored over open flap debridement for both intrabony and furcation defects for primary outcome variables such as clinical probing attachment levels (CPAL), recession (REC), and probing depths (PD). In addition, findings indicated that augmentation of the barrier with bone graft enhanced outcomes in furcation defects.13 Other studies have established that when a non-resorbable barrier is used in combination with DFDBA, 75% of mandibular class II furcation defects demonstrated complete closure of the furcation.14,15 Furthermore, when the horizontal probing depth was less than 5 mm, 85% of the defects showed complete furcation closure.15 When the remaining furcations were evaluated, 68% were converted to class I defects, demonstrating a successful secondary outcome as these are considered maintainable. If both complete closure and conversion to class I defects were assessed, 92% of all sites treated would be considered successful treatment outcomes.

    The use of biologics in periodontal regenerative procedures continues to emerge with two products currently available. These include enamel matrix derivative (EMD) and recombinant human platelet-derived growth factor-BB (rhPDGF-BB). Many reports demonstrate varying levels of success including resolution of intrabony defects and histologic evidence of regeneration using EMD.4,16,17 A systematic review of EMD showed strong evidence of improved CPAL and reduced PD.16 Results on the use of EMD have been comparable to the use of GTR in intrabony defects. Others have shown that the use of EMD in combination with bone grafts appears to enhance outcomes in intrabony defects.18-20 In addition, the use of EMD with osseous autografts in mandibular class II furcation defects demonstrated 36% complete furcation closure, with conversion to class I furcations in all remaining defects.21

    Another biologic used for periodontal regeneration is recombinant human platelet-derived growth factor-BB (rhPDGF-BB), which requires a carrier. A pivotal trial using beta tricalcium phosphate as the carrier with rhPDGF-BB showed an increased CPAL with 56% bone fill of intrabony defects and statistically significant improvement in other clinical parameters.22 A subsequent study depicted histologic regeneration with this material in intrabony defects;5 another showed evidence of regeneration in furcation defects when rhPDGF-BB was used with DFDBA.9

    While individual materials or techniques have been commonly used for regenerative therapy, the trend has been towards the use of combination therapy: employing two or more materials/techniques to improve results. For example, combining a bone graft with GTR enhances the regenerative potential in furcations as well as in other complex osseous defects.12,14,23 Combination therapy appears to maximize results by capitalizing on the various materials’ advantages. Evidence indicates that DFDBA has inductive factors that can enhance new bone formation.24 The use of EMD can induce angiogenesis and promote formation of acellular cementum. GTR inhibits epithelial downgrowth and allows selective cells from the periodontal ligament and bone to fill the defect/wound, improving regeneration. Platelet-derived growth factor has numerous inductive factors critical in the regenerative process. Combining these therapies utilizes the advantages of each individual material and may enhance synergism between them, ultimately providing more options to treat complex osseous defects.

    Regenerative therapy can enhance planned restorative therapy, preserve teeth and their restorations, and enhance or preserve esthetics, thus achieving the optimal goal in dentistry of retaining the natural dentition. The following cases demonstrate indications of selective applications.

    Case 1

    At times teeth are needed as critical abutments. While implant replacement therapy has provided expanded alternatives for patients, fixed partial dentures remain a viable treatment option to replace missing teeth. In a case in which a bridge warranted replacement, the patient did not want to consider implant replacement therapy. A deep, wide intrabony defect was observed on the mesial aspect of tooth No. 31 (Figure 12 and Figure 13), and there was no mobility. The decision was made to use combination regenerative therapy with DFDBA and a resorbable barrier for GTR. The patient was seen for normal postoperative care including ongoing maintenance therapy at 2-3 month intervals. Long-term results (8 years) showed stability with increased bone levels, decreased probing depths, and improved attachment levels (Figure 14).

    Case 2

    While periodontal regenerative therapy can expand options for planned restorative therapy, it can also allow maintenance of teeth that have already been managed with extensive restorations. A patient who relocated and transferred her maintenance care to this author’s practice presented with an intrabony defect on the distal of tooth No. 27 at the time of initial evaluation. Five years earlier she completed full mouth reconstruction that included an implant-supported prosthesis on the maxilla and fixed bridgework that was tooth-supported on the mandible. The patient refused any treatment other than maintenance therapy due to a concern about recession and exposure of the crown margin. When the defect progressed, she agreed to regenerative therapy because of the risk of tooth loss (Figure 15, Figure 16 and Figure 17). The site was managed with a combination of rhPDGF-BB with freeze-dried bone allograft (FDBA) and covered with a resorbable barrier for graft containment. Healing was uneventful, and a 3-year follow up showed radiographic fill of the intrabony defect, improved CPAL, and minimal recession (Figure 18 and Figure 19).

    Case 3

    A patient presented with a history of bridge replacement therapy of teeth Nos. 28 to 30, 2 years prior to initial examination in the periodontal office. Comprehensive periodontal evaluation revealed 14-mm pocketing on the mesial and buccal aspects and slight buccal swelling of tooth No. 27 (Figure 20). Radiographic assessment confirmed extensive bone loss on the mesial aspect and a suggestion of bone loss on the buccal and distal aspects (Figure 21). Treatment options included extraction, ridge augmentation, and implant replacement therapy; extraction and bridge replacement therapy using incisors as abutments and replacing the posterior bridge; and regenerative therapy using combination therapy. The patient preferred to preserve his existing bridge and maintain his natural tooth. At the time of surgery the defect was classified as a buccal dehiscence with a 2-wall intrabony defect on the mesial (Figure 22). Therefore, the site was managed with combination regenerative therapy including EMD, DFDBA, and a titanium-reinforced non-resorbable barrier to help maintain the space and contain the bone graft. Key factors related to the defect/tooth that enabled this type of therapy included minimal mobility, a long root, and good bone levels on the distal and lingual aspects. At 6 weeks, the membrane was removed and revealed significant new tissue filling the defect (Figure 23). The tissue was dense and resisted gentle pressure with the periodontal probe. This was consistent with a rapid healing response.25 Long-term evaluation (9 years) revealed 2-mm probing depth with radiographic improvement consistent with the clinical findings (Figure 24 and Figure 25).

    Case 4

    While there is a paucity of literature on the treatment of dehiscence-type (hidden recession) defects, these lesions occur rather frequently. In addition, it has been suggested that teeth treated endodontically may not be good candidates for regenerative therapy. However, when the diagnosis is accurate (absence of fracture) and treatment is properly performed, there is no evidence that these teeth will not respond favorably to regenerative therapy. In this case, tooth No. 10 exhibited 8-mm pocketing on the facial aspect (Figure 26). Over the previous 4 years, the patient had replaced the crown on this tooth three times. Finally pleased with the color and shape of this crown, the patient was concerned that she might need a new crown after periodontal therapy or possibly lose this tooth, warranting replacement. Treatment was aimed at preserving the tooth and maintaining the current esthetics. Flap reflection revealed a dehiscence defect that extended into the distal interproximal area (Figure 27). After thorough debridement, the site was managed with bone grafting (DFDBA) and GTR using a resorbable barrier. Careful flap management and use of special suturing techniques helped maintain the gingival margin position with minimal-to-no recession. At 11 years post surgery, the crown is still intact with 3-mm probing depth and elimination of the defect (Figure 28). The remaining gingival pigmentation however was not an esthetic concern to the patient.

    Conclusion

    These cases depict the potential that periodontal regeneration can play in preserving the natural dentition. The use of combination therapy enhances success and expands treatment applications. However, limitations do exist, therefore both sites and cases must be carefully selected. Regenerative therapy is technically challenging and warrants precision from the incisional design, material selection, and preparation of the defect to the suturing technique, postoperative care, and subsequent maintenance therapy. While dental implants provide solutions to many problems, regenerative therapy affords patients the opportunity to maintain the natural dentition in health, comfort, function, and esthetics.

    References

    1. Council on Scientific Affairs. American Dental Association. Acceptance Program Guidelines – Determination of Efficacy in Product Evaluation: Products to Regenerate Periodontal Tissues. Chicago, IL: American Dental Association; 1999.

    2. Bowers GM, Chadroff B, Carnevale R, et al. Histologic evaluation of new attachment apparatus formation in humans. Part III. J Periodontol. 1989;60(12):683-693.

    3. Mellonig JT. Enamel matrix derivative for periodontal reconstructive surgery: technique and clinical and histologic case report. Int J Periodontics Restorative Dent. 1999;19(1):8-19.

    4. Yukna RA, Mellonig JT. Histologic evaluation of periodontal healing in humans following regenerative therapy with enamel matrix derivative. A 10-case series. J Periodontol. 2000;71(5):752-759.

    5. Ridgway HK, Mellonig JT, Cochran DL. Human histologic and clinical evaluation of recombinant human platelet-derived growth factor and beta-tricalcium phosphate for the treatment of periodontal intraosseous defects. Int J Periodontics Restorative Dent. 2008;28(2):171-179.

    6. Camelo M, Nevins ML, Schenk RK, et al. Clinical, radiographic, and histologic evaluation of human periodontal defects treated with Bio-Oss and Bio-Gide. Int J Periodontics Restorative Dent. 1998;18(4):321-331.

    7. Stahl SS, Froum S, Tarnow D. Human histologic responses to guided tissue regenerative techniques in intrabony lesions. Case reports on 9 sites. J Clin Periodontol. 1990;17(3):191-198.

    8. Harris RJ. Human histologic evaluation of a bone graft combined with GTR in the treatment of osseous dehiscence defects: A case report. Int J Periodontics Restorative Dent. 2000;20(5):510-519.

    9. Nevins M, Camelo M, Nevins M, et al. Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. J Periodontol. 2003;74(9):1282-1292.

    10. Harris RJ. Treatment of furcation defects with an allograft-alloplast-tetracycline composite bone graft combined with GTR: human histologic evaluation of a case report. Int J Periodontics Restorative Dent. 2002(4);22:381-387.

    11. Tonetti M, Pini-Prato G, Cortellini P. Periodontal regeneration of human intrabony defects. IV. Determinants of healing response. J Periodontol. 1993;64(10): 934-940.

    12. Reynolds MA, Aichelmann-Reidy ME, Branch-Mays GL, Gunsolley JC. The efficacy of bone replacement grafts in the treatment of periodontal osseous defects. A systematic review. Ann Periodontol. 2003;8(1):227-265.

    13. Murphy KG, Gunsolley JC. Guided tissue regeneration for the treatment of periodontal intrabony and furcation defects. A systematic review. Ann Periodontol. 2003;8(1):266-302.

    14. McClain PK, Schallhorn RG. Long-term assessment of combined osseous composite grafting, root conditioning and guided tissue regeneration. Int J Periodontics and Restorative Dent. 1993;13(1):9-27.

    15. Bowers G, Schallhorn R, McClain P, et al. Factors influencing the outcome of regenerative therapy in mandibular Class II furcations: Part I. J Periodontol. 2003;74(9):1255-1268.

    16. Giannobile WV, Somerman MJ. Growth and amelogenin-like factors in periodontal wound healing. A systematic review. Ann Periodontol. 2003;8(1):193-204.

    17. Froum SJ, Weinberg MA, Rosenberg E, Tarnow D. A comparative study utilizing open flap debridement with and without enamel matrix derivative in the treatment of periodontal intrabony defects: A 12-month re-entry study. J Periodontol. 2001;72(1):25-34.

    18. Lekovic V, Camargo P, Weinlaender M, Nedic M, Aleksic Z, Kenney EB. A comparison between enamel matrix proteins used alone or in combination with bovine porous bone mineral in the treatment of intrabony periodontal defects in humans. J Periodontol. 2000;71(7):1110-1116.

    19. Cochran D, Jones A , Heijl L, Mellonig JT, Schoolfield J, King GN. Periodontal regeneration with a combination of enamel matrix proteins and autogenous bone grafting. J Periodontol. 2003;74(9):1269-1281.

    20. Guirinsky BS, Mills MP, Mellonig JT. Clinical evaluation of demineralized freeze-dried bone allograft and enamel matrix derivative versus enamel matrix derivative alone for the treatment of periodontal osseous defects in humans. J Periodontol. 2004;75(10):1309-1318.

    21. Aimetti M, Romano F, Pigella E, Piemontese M. 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. Int J Periodontics Restorative Dent. 2007;27(5):441-447.

    22. Nevins M, Giannobile WV, McGuire MK, et al. Platelet-derived growth factor stimulates bone fill and rate of attachment level gain: results of a large multicenter randomized controlled trial. J Periodontol. 2005;76(12):2205-2215.

    23. Paolantonio M. Combined periodontal regenerative technique in human intrabony defects by collagen membranes and anorganic bovine bone. A controlled clinical study. J Periodontol. 2002;73(2):158-166.

    24. Boyan BD, Ranly DM, McMillan J, Sunwoo M, Roche K, Schwartz Z. Osteoinductive ability of human allograft formulations. J Periodontol. 2006;77(9):1555-1563.

    25. Schallhorn RG, McClain PK. Clinical and radiographic healing pattern observations with combined regenerative techniques. Int J Periodontics Restorative Dent. 1994;14(5):391-403.

    About the Author

    Pamela K. McClain, DDS
    Private Practice
    Aurora, Colorado


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    Image Gallery

    Figure 1  X-ray shows bone loss on the distal aspect and in the area of the furcation of tooth No. 31.

    Figure 1

    Figure 2  Postoperative x-ray depicts bone fill of the defect 2 years after regenerative therapy.

    Figure 2

    Figure 3  Surgical photograph of bone loss in tooth No. 31 buccally and distally.

    Figure 3

    Figure 4  2-year reentry of tooth No. 31 showing complete bone fill in the furcation and distal intrabony defect.

    Figure 4

    Figure 5  Preoperative CPAL of tooth No. 22 mesial was 9 mm.

    Figure 5

    Figure 6  10 years post-regenerative therapy tooth No. 22 CPAL was 3 mm (gain of 6 mm CPAL).

    Figure 6

    Figure 7  Pretreatment radiograph of tooth No. 21 with bony defect on mesial.

    Figure 7

    Figure 8  Radiograph of tooth No. 21 treatedusing a mineralized bone graft at 1 week shows

    Figure 8

    Figure 9  Preoperative x-ray of tooth No. 18. Bone loss is evident on distal aspect.

    Figure 9

    Figure 10  3-month postoperative x-ray of tooth No.18 treated using a demineralized bone graft shows no improvement in bone fill.

    Figure 10

    Figure 11  2-year postoperative x-ray of tooth No. 18 shows bone fill of defect on distal aspect.

    Figure 11

    Figure 12  Surgical photograph of an intrabony defect on the mesial of tooth No. 31.

    Figure 12

    Figure 13  Preoperative radiograph, bone loss on the mesial of tooth No. 31.

    Figure 13

    Figure 14  8-year postoperative radiograph of tooth No. 31 with bone fill on the mesial.

    Figure 14

    Figure 15  Clinical appearance of tooth No. 27 with CPAL of 7 mm.

    Figure 15

    Figure 16  Surgical photograph of tooth No. 27 showing calculus and distal intrabony defect.

    Figure 16

    Figure 17  Preoperative radiograph of tooth No. 27 with bone loss evident on the distal.

    Figure 17

    Figure 18  3-year postoperative radiograph showing bone fill on tooth No. 27 distally.

    Figure 18

    Figure 19   3-year clinical photograph of tooth No. 27 with 3-mm CPAL (gain of 4-mm CPAL)

    Figure 19

    Figure 20  Clinical photograph of tooth No. 27 with buccal PD of 14 mm.

    Figure 20

    Figure 21   Radiograph of tooth No. 27showing extensive bone loss on the mesial.

    Figure 21

    Figure 22  Surgical photograph depicting bone loss on the buccal and mesial aspects of tooth No. 27.

    Figure 22

    Figure 23  GTRmembrane removal shows new tissue 6 weeks following surgery on tooth No. 27.

    Figure 23

    Figure 24  9-year postoperative clinical photograph shows tooth No. 27 with a 2-mm PD.

    Figure 24

    Figure 25  9-year postoperative radiograph of tooth No. 27 shows a resolution of the defect.

    Figure 25