J Periodontol June 2008

Commentary
Strategic Extraction: A Paradigm Shift That Is Changing Our Profession
Richard T. Kao*

The greatest challenge in treatment planning is to assign an accurate prognosis and develop a predictable protocol. In the era of evidence-based dentistry, outcome studies have forced us to reexamine our treatment approaches and decide if superior treatment options should be pursued. As endosseous dental implants gain greater acceptance because of high success rates, the critical question is whether a tooth with a questionable prognosis should be managed conservatively in a traditional fashion or be strategically extracted in preparation for a dental implant. The outcomes of traditional periodontal, endodontic, and prosthodontic treatment approaches are compared to the option of strategic extraction. J Periodontol 2008;79:971-977. KEY WORDS Dental implants; prognosis; treatment.

trategic extraction originally described the removal of a tooth or root to create a more hygienic environment.1,2 The objective was to enhance the status and prognosis of an adjacent tooth or the overall prosthetic treatment plan, i.e., eliminate the high-risk element to improve the overall periodontal prosthetic prognosis. Prosthodontists began using this strategy to extract teeth that did not contribute to the removable partial denture design or compromised the nal xed prosthesis. Orthodontists expanded this concept of the extraction of healthy teeth in crowded dentition to achieve ideal occlusion. With the acceptance of dental implants and the use of recombinant biologic modiers for implant site preparation, strategic extraction merits reexamination. The decision to apply strategic extraction is based on each clinicians prognosis for each individual tooth as well as the overall dentition. Although there is some general agreement, there are subtle differences among practitioners based on opinions about what tooth or teeth can be successfully treated. These differences are the result of our personal clinical experiences, interpretation of the literature, and techniques at our disposal. With strategic extraction, the prognostic decision process is essentially the weighing of one option against another to determine which offers the best chance of success. As implants become a more accepted treatment, it is important to assess their value compared to other treatment modalities. Selecting implant treatment is essentially a decision to use strategic extraction, but there have been few articles3-5 on this subject. This commentary examines the therapeutic outcomes of placing dental implants compared to periodontal, prosthetic, and endodontic treatment options.

COMPARISON OF TREATMENT OPTIONS Comparing treatment options is a complex balance between relying on evidence-based dentistry and personal clinical experience.6 Nevertheless, the principles of evidence-based dentistry require us to be
* Private practice, Cupertino, CA; Division of Periodontology, University of California at San Francisco, San Francisco, CA; Department of Periodontology, University of the Pacic, San Francisco, CA. doi: 10.1902/jop.2008.070551

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familiar with outcome studies for the various treatment options. Periodontal Considerations Determining an accurate prognosis for each individual tooth and for the overall dentition is difcult. Forecasting individual tooth prognoses is usually based on clinical and radiographic parameters (e.g., radiographic bone loss, probing depths, clinical attachment levels, bleeding on probing, furcation involvement, and mobility). Classic studies by Hirschfeld and Wasserman7 and other investigators8-10 showed that even with highly compliant patients, it is almost impossible to predict the survival of a periodontally compromised tooth. During the period these patients were maintained, tooth loss ranged from 6.2% to 9.8%, with an annual average of 0.08% to 0.11%. Tooth loss for the treated, but not maintained, population was higher, with an annual tooth loss rate of 0.22%.10 These studies also generally indicated that it is more difcult to accurately forecast the prognosis of teeth with furcations and/or the multirooted tooth versus the singlerooted tooth. In a series of articles, McGuire and Nunn11-13 determined that clinical parameters were ineffective in predicting any outcome other (than those teeth with) good prognosis.13 The forecasting accuracy for teeth assigned a good prognosis was 81% after 8 years, but this decreased to 35% when applied to teeth with an initial prognosis of less than good.12 In a recent literature survey,5 the long-term retention of teeth with questionable prognoses ranged from 38% to 97%. A direct comparison of these studies is not possible because of differences in subject populations, clinical evaluation parameters, maintenance methods, and the number/type of teeth monitored. Most importantly, there were no standard criteria to dene a questionable prognosis. Extensive research efforts have focused on clinical parameters as predictors of disease progression. Bleeding on probing is a poor predictor of periodontal disease progression, and its absence on sequential visits was shown to be a good predictor of no future attachment loss.14 Several retrospective studies7-9 suggested furcation involvement was one of the main reasons for tooth loss. In a review of therapeutic outcomes, retention rates of furcated teeth ranged from 43% to 98%, suggesting that the actual retention rate is better than the long-term prognostication.5 Tooth mobility has also been proposed as a risk factor for attachment and tooth loss,15,16 but other reports suggest hypermobility is not always associated with advanced disease progression17 or worsening prognosis.12 Some studies18-20 suggested that deep probing depths predict future attachment loss; however, another study20 suggested that this relationship is
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not absolute. Deep probing depth seems to be associated with a higher risk for further attachment loss compared to shallow probing depth; however, further disease progression is not inevitable, although treatment can reduce this possibility. It is the absence of deep probing depth, similar to bleeding on probing, which is a good forecaster of periodontal stability. These clinical parameters have not been reliable forecasters of disease activity. In addition to the lack of reliable prognostic determinants for periodontal stability, the clinician is hampered by patient management issues that may complicate the periodontal forecast. The rst issue is patient compliance with home care instructions and maintenance therapy appointments. Studies21-23 indicated that 20% to 30% of treated patients do not comply with the recommended maintenance therapy, and of those who do comply, approximately half are erratic in their care. As expected, erratic compliers require more retreatment compared to patients who follow home care guidelines and regularly present for maintenance.23 The second issue is systemic disease risk factors, such as smoking, diabetes, and immunosuppression; these are not within the scope of this discussion, but they contribute to the difculty of periodontal evaluation. When analyzed in conjunction with the clinical parameter studies, these two issues result in a confounding combination of information. Like statistics where the odds that an event may occur under one situation are analyzed in a myriad of situations, the results are not additive, but synergistic. This is where the art of periodontal prognosis begins and why our opinions vary so widely. The decision to extract or preserve a tooth should be based on knowledge of the literature, accurate collection of clinical information (clinical parameter data and medical-social history), our past clinical experiences, and consideration of the patients values. But exactly when should strategic extraction be invoked? How should teeth with a questionable prognosis be managed? It is important to recognize that periodontal therapy and prognosis is not a static process. Despite the limited success associated with some treatments, the option for therapy and a chance for disease control are determined, in part, by the clinicians skills and information in the literature. The critical part of this decision is based on the discussion with the patient to determine his/her preferences. If the decision is made to begin periodontal treatment to control the disease, then reevaluation of the clinical response will result in a new prognosis. Similarly, maintenance requires constant monitoring and reformulation of the prognosis. Periodontal prognosis is shaped by how the clinical condition responds to our periodontal management and the patients home

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care. At any point in this process, the relative value of strategic extraction must be reviewed with the patient. The decision about strategic extraction should be made when a potential implant site is in danger because of continual bone loss, and it should be based on to what extent we can still predictably offer the patient the implant option. Endodontic Therapy Classically, when a tooth has a pulpal involvement secondary to tooth fracture and carious lesion, endodontic therapy has been the treatment of choice. However, dental implants have become an alternative for such therapy. In a systematic review24 of the endodontic literature, the survival rate after root canal treatment followed by coronal restoration ranged from 81.2% to 100% over 3 to 25 years. In the same review,24 the survival rates of single-tooth implants and restored endodontically treated teeth were statistically similar after 5 to 7.8 years. The investigators concluded that the decision to treat a compromised tooth endodontically or replace it with an implant should be based on factors other than treatment outcome. Endodontic factors to be considered include the presence/absence of a periapical lesion, the type of endodontic treatment, and the postendodontic restorative situation. The presence of preoperative periapical lesions decreases the endodontic success rate by 10%.25 A recent study26 reported that in the absence of such lesions, the healing rate was 94% compared to 79% in sites with lesions. Approximately 45% of the lesions slowly decreased in size. This has been interpreted as slow but progressive healing. Approximately 6% of the teeth had a persistent lesion 10 years after treatment.26 Endodontic retreatment can signicantly reduce the 97% success rate seen with initial endodontic therapy.27-29 Surgical retreatment of a poorly endodontically lled tooth can reduce the success rate by as much as 13% to 29%, with a reported mean healing rate of 78%.30,31 These ndings are consistent with a recent review28 that suggested the chance of success ranged from 37% to 85%, with an average of 70%. In one study29 of endodontic retreatment, perforations were seen in 12% of the cases; the outcome and prognosis were so poor that these teeth were excluded from analysis. These studies suggest that surgical retreatment of root perforation and poor root-lling quality are strong predictors of poor endodontic outcome. Periapical lesions, root perforations, and poor endodontic ll are factors that complicate endodontic evaluation; the restorability of the endodontically treated tooth is of greater importance. A systematic review24 suggested that root canal treatment followed

by coronal restoration has a success rate similar to implants. The review has limited value because of the short mean time (7.8 years) used to evaluate tooth survival, the assumption that all endodontically treated teeth will be coronally restored, and because monitoring occurred after restorations were placed. The evaluation period may be too short to support the assumption that all endodontically treated teeth can be successfully restored. The clinical reality is that not all endodontically treated teeth are restored; other factors, such as postplacement fracture or perforation, types of posts inserted, form of supracoronal restorations, and prosthetic issues, were not addressed and may have resulted in an overestimation of the success rate. In a survey32 of 12 studies with a 6-year followup, 10% of teeth with posts had complications. Other complications that occurred with conventional single crowns included crown fracture (7%), loss of retention (2%), post and core loosening (5%), root fracture (3%), and caries (3%).32 Some studies33-35 reported that 24.2% to 85% of root canaltreated teeth were extracted because they were not properly restored. Until there are more outcome studies that evaluate these individual factors, equating the success rate of endodontically treated teeth to that of implants should be accepted with the caveat that there are limitations to this comparison. Prosthetic Therapy There are limited longitudinal studies assessing the survival of xed partial dentures (FPDs) to replace missing teeth. Additionally, the results are difcult to analyze because of different follow-up periods and denitions of failure. The only meta-analysis36 that assessed the overall effectiveness of FPD therapy reported that <15% of FPDs had been removed or needed replacement at 10 years; the gure increased to nearly one-third after 15 years. In another study,32 the three most commonly reported FPD complications were caries (18% of abutments), need for endodontic treatment (11% of abutments), and loss of retention (7% of prosthesis). These complications are costly nancially and often require additional procedures that increase the chances for failure. Implants The efcacy and predictability of endosseous implants in treating partially and totally edentulous cases have been well documented.37-39 Regardless of the implant system used, functional success was achieved in >90% of the patients after 8 to 15 years.37,38 In situations involving limited bone volume, socket or ridge preservation, guided bone regeneration, and distraction osteogenesis can be effective ridge-enhancement techniques.40,41 Nevertheless, the principle challenges in implant dentistry are to regenerate adequate bone volume and clinical esthetics.
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Although implant survival and function success rates are high, there are clinical complications. According to a review by Goodacre et al.,42 the most common surgical complications were hemorrhage related, mostly hematomas and ecchymosis (24%), followed by neurosensory disturbance (7%), and mandibular fracture (0.3%). However, most of the bleeding and neurosensory situations were transitory and had no effect on long-term implant success.42 Other complications included implant loss in irradiated maxillae (25%), type IV bone (16%), and patients with diabetes (9%).42 These latter complications and those observed with mandibular fracture are more accurately identied as issues relating to case selection and evaluated as implants placed in compromised sites or in high-risk patients. Prosthetic complications included loosening of the overdentureretentive mechanism (33%), resin veneer fracture with xed partial dentures (22%), implant loss with maxillary overdentures (21%), overdentures needing to be relined (19%), and overdenture clip/attachment fracture (16%).42 Most prosthetic complications are related to the use of implants with overdentures or xed removable prostheses. Although these issues may be classied as complications, most of them are normal events associated with prosthetic maintenance and are generally correctable. From a functional perspective, esthetic complications occurred with a mean prevalence of 10%, and phonetic complications occurred with a mean prevalence of 7%. From this survey, Goodacre et al.42 concluded that implants and implant prostheses had a trend toward a greater incidence of complications compared to single crowns, FPDs, all-ceramic crowns, resin-bonded prostheses, and post and cores. Although the incidence rate may be higher, most of the situations identied can be resolved with no long-term negative consequences. Lastly, the data collected included a wide cross-section of implants used in compromising situations, such as removable denture design, or in highrisk patients. DISCUSSION Strategic extraction has been and will continue to be a subject of debate, with no clear algorithm for decision making. In the review of periodontal, endodontic, and prosthetic options by Goodacre et al.,42 the conclusion is that this decision-making process is difcult. As we compile outcome data, we start to understand that any clinical situation may have a multitude of factors that need to be considered before a treatment plan is developed. An example is a carious pulpal exposure on a tooth with a furcation involvement. Instead of considering only the outcome of endodontic treatment, we need to consider the periodontal prognosis of the furca, the success rate of the post and core
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placement, and the long-term crown survival. With many situations, we may know the probability of successful outcome for any single aspect, but when there are so many confounding factors, the possibility of successful treatment decreases. In addition, the patients concern over losing a tooth, possible changes in esthetics, and the length and cost of treatment must be considered in the decision-making process. Because of the high success rate of dental implants, there are concerns that teeth with a guarded prognosis will be prematurely extracted to be replaced with dental implants.5 Although this author shares some of these concerns, the critical premise on which strategic extraction should be based is: Do not take a stance of watchful waiting. That is, do not postpone extraction until the situation deteriorates to the point where other options are eliminated or compromised. In many situations, implants provide a good functional option with acceptable esthetics. A major key to implant success is adequate bone volume: ideally, native bone. Strategic extraction should be considered if other therapeutic options compromise the potential to obtain or preserve this bone volume. Situations in which this guiding principle may not apply are elderly patients if there are other serviceable options, when satisfactory esthetic results cannot be achieved, or when the patient objects to a perceived premature tooth loss. One of the main limitations to successful implant placement is inadequate bone volume at the recipient site. Our ability to work with compromised sites has improved with the variety of techniques available for increasing bone volume through ridge preservation, augmentation, sinus grafting, and distraction osteogenesis.40,41 Incorporating recombinant biologic modiers in regenerative therapeutics further increases the possibility of success. Within the past 2 years, the United States Food and Drug Administration (FDA) has approved two recombinant protein therapeutic products: recombinant human platelet-derived growth factor (rhPDGF)-BB and recombinant human bone morphogenetic protein (rhBMP)-2. rhPDGF has been used in the treatment of severe periodontal intrabony and Class II furcation defects,43-45 and its potential use in bone augmentation procedures46,47 and soft tissue reconstruction47,48 may improve implant site development. Similarly, rhBMP has been used successfully for bone augmentation in the maxillary sinus oor, extraction sites, and alveolar ridge defects.49,50 Three obstacles have prevented the rapid incorporation of these products into clinical practice. The rst is that the exact requirements for clinical use are being rened. The ideal carrier/regenerative scaffolding is still being explored to optimize release kinetics and to serve as scaffolding for the early cellular events

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associated with bone formation. rhPDGF and rhBMP-2 exhibit a biphasic mode of action. Three concentrations of rhPDGF were used in the FDA trial. The intermediate concentration of 0.3 mg/ml proved optimal for periodontal regeneration, whereas the other two concentrations yielded a lower response.45,51 This was also true in rhBMP-2 studies;50,52 the lower concentrations (0.43 and 0.75 mg/ml) were less effective for ridge preservation than the highest concentration (1.5 mg/ml). These optimal concentrations were established for a specic defect situation, and it remains to be determined if these concentrations deliver the optimal regenerative response under different clinical situations. These are challenges that clinicians using these biologic modiers need to address through clinical studies. The second issue is whether the regenerated bone possesses adequate bone quality, especially in terms of bone density, to support implant osseointegration. The third issue is the relatively high cost for one of these products. Given the current cost, it is difcult for clinicians to incorporate them into practice until there is clear evidence of technique superiority and well-documented treatment protocols are established. However, these recombinant biologic modiers seem to hold great promise and may change how we dene the critical time point to implement strategic extraction. CONCLUSIONS Although periodontists are viewed by the dental profession as experts in forecasting tooth prognosis, we have no infallible method for making these decisions. Although there is an ingrained tendency to try to save teeth, we must remember that our therapy works best with good patient compliance. Additionally, should our results be unsuccessful, we must readily consider other options, including strategic extraction. As we increasingly accept evidence-based dentistry as a basis for practice decisions, we discover that limited outcome studies are the foundation for this approach to treatment. Further complicating the decision-making process is the fact that many clinical situations require us to consider a multitude of confounding factors. Nevertheless, we recognize that there is a critical point where elective or strategic extraction is the best solution for dealing with compromised dentition. Because of the high success rate of dental implants, this critical point has shifted toward an earlier strategic extraction to preserve the bone volume necessary for implant placement. Additionally, with the availability of recombinant biologic modiers, this critical point may shift again. The critical point for each practitioner will reect individual interpretations of the outcome studies discussed above and personal experience. It is important to reemphasize that patient age, personal preferences, and -

nances must always be part of the decision-making process. In summary, because of the acceptance of dental implants, the emergence of biologic modiers, and growing reliance on evidence-based dentistry, our profession needs to change its view of prognosis and its clinical implications for treatment. It is imperative that we understand this situation and alter our educational focus to adequately prepare periodontists for this future. ACKNOWLEDGMENT The author reports no conicts of interest related to this study. REFERENCES
1. Corn H, Marks MH. Strategic extractions in periodontal therapy. Dent Clin North Am 1969;13:817-843. 2. Rosenberg MM, Kay HB, Keough BE, Holt RL. Initial therapy phase. In: Rosenberg MM, Kay HB, Keough BE, Holt RL, eds. Periodontal and Prosthetic Management for Advanced Cases. Chicago: Quintessence Books; 1988:73-79. 3. Davarpanah M, Martinez H, Tecucianu JF, Fromentin O, Celletti R. To conserve or implant: Which choice of therapy? Int J Periodontics Restorative Dent 2000; 20(4):413-422. 4. Mordohai N, Reshad M, Jivraj SA. To extract or not to extract? Factors that affect individual tooth prognosis. J Calif Dent Assoc 2005;33:319-328. 5. Greenstein G, Greenstein B, Cavallaro J. Prerequisite for treatment planning implant dentistry: Periodontal prognostication of compromised teeth. Compend Contin Educ Dent 2007;28:436-447. 6. Kao RT. The challenges of transferring evidence-based dentistry into practice. J Evid Based Dent Pract 2006; 6:125-128. 7. Hirschfeld L, Wasserman B. A long-term survey of tooth loss in 600 treated periodontal patients. J Periodontol 1978;49:225-237. 8. McFall WT Jr. Tooth loss in 100 treated patients with periodontal disease. A long-term study. J Periodontol 1982;53:539-549. 9. Becker W, Berg L, Becker B. The long-term evaluation of periodontal treatment and maintenance in 95 patients. Int J Periodontics Restorative Dent 1984;4: 54-71. 10. Becker W, Becker B, Berg L. Periodontal treatment without maintenance. A retrospective study in 44 patients. J Periodontol 1984;55:505-509. 11. McGuire MK. Prognosis versus actual outcome: A long-term survey of 100 treated periodontal patients under maintenance care. J Periodontol 1991;62: 51-58. 12. McGuire MK, Nunn ME. Prognosis versus actual outcome. II. The effectiveness of clinical parameters in developing an accurate prognosis. J Periodontol 1996;67: 658-665. 13. McGuire MK, Nunn ME. Prognosis versus actual outcome. III. The effectiveness of clinical parameters in accurately predicting tooth survival. J Periodontol 1996;67: 666-674. 14. Lang NP, Adler R, Joss A, et al. Absence of bleeding on probing. An indicator of periodontal stability. J Clin Periodontol 1990;17:714-721. 975

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15. Fleszar TJ, Knowles JW, Morrison EC, Nyman S. Tooth mobility and periodontal therapy. J Clin Periodontol 1980;7:495-505. 16. Wang HL, Burkett FG, Sheer Y, et al. The inuence of molar furcation involvement and mobility on future clinical periodontal attachment loss. J Periodontol 1994; 65:25-29. 17. Ericsson I, Giargia M, Lindhe J, et al. Progression of periodontal tissue destruction at splinted/non-splinted teeth. J Clin Periodontol 1993;20:693-698. 18. Badersten A, Nilveus R, Englberg J. Scores of plaque, bleeding, suppuration and probing depth to predict probing attachment loss. 5 years of observation following nonsurgical periodontal therapy. J Clin Periodontol 1990;17:108-114. 19. Nordland P, Garrett S, Kiger R, et al. The effect of plaque control and root debridement in molar teeth. J Clin Periodontol 1987;14:231-236. 20. Claffey N, Egelberg J. Clinical indicators of probing attachment loss following initial periodontal treatment in advanced periodontitis patients. J Clin Periodontol 1995;22:690-696. 21. Wilson TG Jr., Hale S, Temple R. The results of efforts to improve compliance with supportive periodontal treatment in a private practice. J Periodontol 1993;64: 311-314. 22. Mendoza A, Newcom G, Nixon K. Compliance with supportive periodontal therapy. J Periodontol 1991;62: 731-736. 23. Schmidt J, Morrison E, Kerry G, Caffesse R. Patient compliance with suggested maintenance recall in private periodontal practice. J Periodontol 1990;61: 316-317. 24. Iqbal MK, Kim S. For teeth requiring endodontic treatment, what are the differences in outcomes of restored endodontically treated teeth compared to implant-supported restorations? Int J Oral Maxillofac Implants 2007;22(Suppl.):96-116. 25. Sjogren U, Hagglund B, Sundqvist G, Wing K. Factors affecting the long-term results of endodontic treatment. J Endod 1990;16:498-504. 26. Farzaneh M, Abitbol S, Lawrence HP, Friedman S. Treatment outcome in endodontics The Toronto Study. Phase II: Initial treatment. J Endod 2004;30:302-309. 27. Friedman S. Treatment outcome and prognosis of endodontic therapy. In: Orstavik D, Pitt Ford TR, eds. Essential Endodontology. Oxford, U.K.: Blackwell Science; 1996:367-401. 28. Farzaneh M, Abitbol S, Friedman S. Treatment outcome in endodontics: The Toronto Study. Phase I and II: Orthograde retreatment. J Endod 2004;30:627633. 29. Friedman S, Mor C. The success of endodontic therapy Healing and functionality. J Calif Dent Assoc 2004;32:493-503. 30. Molven O, Halse A, Fristad I, MacDonald-Jankowski D. Periapical changes following root-canal treatment observed 20-27 years postoperatively. Int Endod J 2002;35:784-790. 31. Sundqvist G, Figdor D, Persson S, Sjogren U. Microbiologic analysis of teeth with failed endodontic treatment and the outcome of conservative re-treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:86-93. 32. Goodacre CJ, Bernal G, Rungcharassaeng K, Kan JY. Clinical complications in xed prosthodontics. J Prosthet Dent 2003;90:31-41. 976

33. Salehrabi R, Rostein I. Endodontic treatment outcomes in a large patient population in the USA: An epidemiological study. J Endod 2004;30:846-850. 34. Aquilino SA, Caplan DJ. Relationship between crown placement and the survival of endodontically treated teeth. J Prosthet Dent 2002;87:256-263. 35. Sorensen JA, Martinoff JT. Endodontically treated teeth as abutments. J Prosthet Dent 1985;53:631636. 36. Scurria MS, Bader JD, Shugars DA. Meta-analysis of xed partial denture survival: Prostheses and abutments. J Prosthet Dent 1998;79:459-464. nemark PI. A 37. Adell R, Lekholm U, Rockler B, Bra 15-year study of osseointegrated implants in the treatment of the edentulous jaw. Int J Oral Surg 1981;10: 387-416. 38. Jemt T, Lekholm U, Adell R. Osseointegrated implants in the treatment of partially edentulous jaws: A preliminary study on 876 consecutively placed xtures. Int J Oral Maxillofac Implants 1989;4:211-217. 39. Buser D, Mericske-Stern R, Bernard JP, et al. Longterm evaluation of non-submerged ITI implants. Part 1: 8-year life table analysis of a prospective multi-center study with 2,359 implants. Clin Oral Implants Res 1997;8:161-172. 40. Fiorellini JP, Nevins ML. Localized ridge augmentation/ preservation. A systematic review. Ann Periodontol 2003;8:321-327. 41. Wallace SS, Froum SJ. Effect of maxillary sinus augmentation on the survival of endosseous dental implants. A systematic review. Ann Periodontol 2003;8: 328-343. 42. Goodacre CJ, Bernal G, Rungcharassaeng K, Kan JY. Clinical complications with implants and implant prostheses. J Prosthet Dent 2003;90:121-132. 43. Nevins M, Camelo M, Nevins ML, Schenk RL, Lynch SE. Periodontal regeneration in humans using recombinant human platelet-derived growth factor BB (rhPDGF-BB) and allogenic bone. J Periodontol 2003; 74:1282-1292. 44. Camelo M, Nevins ML, Schenk RK, Lynch SE, Nevins M. Periodontal regeneration in human Class II furcations using puried recombinant human plateletderived growth factor-BB (rhPDGF-BB) with bone allograft. Int J Periodontics Restorative Dent 2003; 23(3):213-225. 45. Nevins M, Giannobile W, McGuire MK, et al. Plateletderived growth factor stimulates bone ll and rate of attachment level gain: Results of a large multicenter randomized controlled trial. J Periodontol 2005;76: 2205-2215. 46. Simion M, Rocchietta I, Kim D, Nevins M, Fiorellini J. Vertical ridge augmentation by means of deproteinized bovine bone block and recombinant human plateletderived growth factor-BB: A histologic study in a dog model. Int J Periodontics Restorative Dent 2006; 26(5):415-423. 47. Fagan MC, Miller RE, Lynch SE, Kao RT. Simultaneous augmentation of hard and soft tissues for implant site preparation using recombinant human platelet-derived growth factor: A human case report. Int J Periodontics Restorative Dent 2008;28(1): 37-43. 48. McGuire MK, Scheyer ET. Comparison of recombinant human platelet-derived growth factor-BB plus beta tricalcium phosphate and a collagen membrane to subepithelial connective tissue grafting for the treatment

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of recession defects: A case series. Int J Periodontics Restorative Dent 2006;26(2):127-133. 49. Boyne PJ, Lilly LC, Marx RE, et al. De novo bone induction by recombinant human bone morphogenetic protein-2 (rhBMP-2) in maxillary sinus oor augmentation. J Oral Maxillofac Surg 2005;63:1693-1707. 50. Fiorellini JP, Howell TH, Cochran D, et al. Randomized study evaluating recombinant human bone morphogenetic protein-2 for extraction socket augmentation. J Periodontol 2005;76:605-613. 51. Howell TH, Fiorellini JP, Paquette DW, et al. A phase I/II clinical trial to evaluate a combination of recombinant human platelet-derived growth factor-BB and recombinant human insulin-like growth factor-I in

patients with periodontal disease. J Periodontol 1997; 68:1186-1193. 52. Cochran DL, Jones AA, Lilly LC, et al. Evaluation of recombinant human bone morphogenetic protein-2 in oral applications including the use of endosseous implants: 3-year results of a pilot study in humans. J Periodontol 2000;71:1241-1257. Correspondence: Dr. Richard T. Kao, 10440 S. DeAnza Blvd., Suite #D-1, Cupertino, CA 95014. Fax: 408/2529596; e-mail: richkao@sbcglobal.net. Submitted October 15, 2007; accepted for publication December 3, 2007.

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