Periodontics

The use of enamel matrix protein in the treatment of iocaiized : A case report

Hernán Bonta, DDSVFernando Llambes, DDS^/Antonio J. Moretti, DDS, Hiru Mathur, DDS, MSVOtis J. Bouwsma, MS, PhD,

The previously named localized juvenile periodontitis (LJP), recently reclassified as localized aggressive periodcntitis (LAP) seen in young people, is a rare condition characterized by severe periodchtal destruc- tion arotjnd firsf molars and incisors in individuals with little or ho accumulation of visible plaque and/or . Treatment of this condition has tradificnally included periodonfal surgery and adjunctive antibiotic therapy. Even though several pericdontal regeneration techniques in these patients have been reported, there have been no reports of the use of the enamel matrix proteins in the treatment of intrabony defects caused by this disease. This report describes the case of a 15-year-old patient who was diagnosed as having LAP and the resulting treatment and outcome. The treatment consisted of systemic antibiotic ther- apy and periodcntal surgical procedures combined with enamel matrix protein application.The 6-month clinical probing and attachment level measurements and radiographie findings are reported. (Quintessence Int 2003:34:247-252)

Key words: attachment level, enamel matrix proteins, intrabony defect, localized aggressive periodontitis, periodontal regeneration, probing depth

he literature has described rapid periodontal at- the Classification of and Ttachment loss in young adults. The initial designa- Conditions,^ patiicipants agreed to discard classifica- tion was and was introduced by tion terminologies that were age dependent. Therefore, Gottlieb in 1923,' It was believed that this disease was the terms Iocaiized and generalized juvenile periodon- atrophie in nature. The term juvenile periodontitis was titis (LJP, GJP) have been renamed as localized and introduced in 1969,^ and was further clarified by generalized aggressive periodontitis (LAP, GAP). Baer,^ who defined the disease as a rapid loss of alveo- The prevalence of LAP varies according to the di- lar bone in the permanent dentition of adolescents agnostic criteria, geographies, and the diverse data- with minimal clinical signs of inflammation. Two base of the different studies.'-^ The largest epidemio- forms have been described; a generalized form (seen logic study performed in the United States reported an in late teens) and a locahzed form (seen around pu- overall prevalence of 0.53% between the ages of 14 berty) affecting mainly first molars and incisors.'^ and 17 years'"; however, blacks had a higher preva- During the most recent Ititernational Workshop for lence than whites (2.64''/o versus 0.17%), Among blacks, males were 2.9 times more likely to have LAP than females. Several factors appear to be involved in 'Prívale Practice, Buenos Aires, Argentina. the etiology and pathogenesis of this condition. ^Private Practice, Valencia, Spain. Newman et al" and Newman and Socransky'^ carried 'Assistant Professor, Department of Endodontics and Peiiodontics, out investigations on the specific microbial compo- University ot Texas Healtti Science Center at Houston Dental Branch, nents present in LAP. Actinobacillus actinomycetem- Hojslor, Texas. comitans (Aa) and are the most 'Ciirncai Assistant Professor, Department of Endodontics and Periodontics, common pathogens identified.'^"'' The high virulence University of Texas htealtfi Science Center at Houston Dental Branch, and pathogenic potential of Aa is due to the produc- iHouston, Texas. tion of leukotoxins, endotoxins, chemotactic inhibi- =Associate Professor and Graduate Piogram Director in Penodonlics, Department of Endodontics and Peiiodonlics, University of Texas Health tion factors, and collagenase. In addition, host re- Science Cenler at Hojston Dental Branch, Houston, Texas. sponse plays a major role in the pathogenesis of this Reprint requests: Dr Otis J. Bouwsma, Department of Endodonlics and condition, Immunologie deficiencies have been de- Periodontics, University of Texas Heaith Science Centei at Houston Dental tected in many cases in which lymphocyte activity,'^ Branch, Room 375A, S516 M.O. Anderson Boulevard, Houston, Texas function of polymorphonuclear leukocytes," antibody 77030. E-mail: OtJs.J.Boü[email protected],edu

Quintessence International 247 Bonta et al

LAP. Medical, dental, and family histories were not TABLE 1 Probing depth and attactimetit level measurements (mm) at baseline and 6 motiths clinically significant posttreatment and resultant probitig depth A complete clinical and radiographie examination reduction and clinical attachment gain revealed several small carious lesions. The initiai O'Leary plaque control record^' was 30%. In general, Clinical attachment Probing depth (PD) level (CAL) gingival tissues presented with a pink color, firm tex- ture, and adequate contour. Probing depth (PD) mea- PD CAL Tooth/site Baseline 6 mo reduction Baseline 6 mo gam surements ranged from 1 to 10 mm, with the most se- vere sites being present around tbe maxillary rigbt 16 first molar (tooth 16[3]) and the mandibular left first Mesiobticcai 9 4 5 8 3 5 Mesiopaiatal 6 3 3 5 2 3 molar (tootb 36[19]), Clinical attacbment level (CAL) 36 ranged from 0 to 9 mm, and again tbe greatest loss Mesiobuccal 10 3 7 9 2 7 was found at teetb 16 and 56 (Table 1}. Bleeding on Mesiolingual 6 3 3 5 2 3 probing was localized at the mesiobuccal and mesiopaiatal surface of tooth 16 and tbe mesiolingual surface of tooth 36. No furcation involvement or in- creased mobility was detected. Radiographically, production,'* and complement activation'^ are af- mesial vertical bony defects were associated witb both fected, A genetic component is likely to be present in teeth 16 and 36 (Figs 1 and 2), Initial tberapy in- LAP since some studies have shown an increased cluded Instruction and scaling and root prevalence among certain family groups.^" planing. Probing deptbs following initial therapy were The elimination of Aa is orte of the main goals of virtually uncbanged. Following consultation with the treatment. This can lead to the arrest of the disease patient and bis parents, it was decided tbat tbe patient and allow an environment in which healing can occur. would benefit from reduction in probing depths. To Continued suppression of Aa is apparently critical for achieve this goal, periodontal surgeries were suggested posttreatment periodontal stability. Nonsurgical and on teetb 16 and 36, and the patient and bis family surgical therapy with or without adjunctive use of an- agreed. Full tbickness, mucoperiosteal flaps were ele- tibiotics has shown reasonable success in controlling vated in both areas, the defects were debrided, and attachment loss.^'-^* A number of approaches have tbe roots were scaled and root planed. A large two- been suggested for restoration of the lost periodon- walled circumferential bony defect of 5 mm in depth tium. A wide variety of materials, including bone (from the hone crest to tbe most apical portion of the grafts, bave been used in conjunction witb surgical defect) was found on the mesial sitrface of tooth 16 procedures witb tbe goal of acbieving periodontal re- (Fig 3). A large two/three-walled bony defect of 6 tnm generation wben treating LAP."-^^ However, tbere has in depth (from tbe bone crest to the most apical por- been little or no evidence regarding tbe type of perio- tion oí the defect) was detected on the mesial surface dontal attacbment obtained after tbese procedures in of tooth 36 (Fig 4). Root surfaces were conditioned LAP patients. Enamel matrix proteins (Emdogain, with 24% ethylenediaminetetraacetic acid (EDTA) at Biora) bave been sbown to produce periodontal re- a neutral pH (PrefGel, Biora) for 2 minutes. After irri- generation in some cases.^^'^' Human histology has gation of the sites with sterile saline to remove EDTA, demonstrated tbat tbe formation of new bone, cemen- a gel containing enamel matrix proteins (Emdogain, tum, and periodontal ligament can be ohtalned follow- Biora) was applied to the root surfaces. The flaps then ing the use of this material,^'•^•' This report describes were repositioned and single, interrupted Vicryl 4/0 ibe clinical and radiographie outcomes following use (Ethicon) sutures were placed, which resulted in pri- of enamel matrix proteins in the treatment of localized mary closure. Postoperative care included 100 mg aggressive periodontitis in a 15-year-old patient. doxycycline hyclate per day for 3 weeks (200 mg only on the first day)'«-^* and a 0.12% diglu- conate mouthrinse twice daily for 6 weeks. The su- tures were removed 14 days after surgery, and profes- CASE DESCRIPTION AND RESULTS sional supragingival plaque control was scheduled every 2 weeks during the first 6 months following A 15-year-old black male was referred to the surgery,5«-'"' Healing was uneventful. There was a Periodontics Postgraduate Clinical Service at Tbe marked improvement in botb clinical and radio- University of Texas Health Science Center Houston graphic parameters at 6-month postsurgery examina- Dental Branch, for periodontal diagnosis and treat- tion, (Table 1, Figs 5 and 6), ment. The patient was diagnosed as having untreated

248 • Bonta et al •

Fig 1 Periapical radiograptí of the maxillary right first molar prior Fig 2 Periapical radiograph of the mandibular ieft tirst moiar prior to treatment.

Fig 3 Surgical view of intrabony defect on mesiai paiatal side ot Fig 4 Surgicai view of intrabony defect on mesial palatai side of the maxillary right first molar. the mandibular lefL first molar.

Fig 5 Periapical radiograph of the maxillary right firsi mo[ar 6 Fig 6 Periapioai radiograph of the mandibuiai ieft first moiar 6 months after surgical treatment. months after surgical treatment

Quintessence International 249 • Bonta et al •

DISCUSSION The current study is the first known report in the literature describing the use of these proteins in intra- Localized aggressive periodontitis (previously called lo- bony defects in patients with localized aggressive peri- calized juvenile periodontitis) has been described as a odontitis. The patient in this case report presented form of periodontai disease seen in young people char- with several typical features associated with LAP, acterized by severe periodontai destruction with little Clinically, the patient presented with deep intrabony or no visible accumulation of plaque or calculus,^"" defects at the first molars (teeth 16 and 36}, After Several treatment strategies have been implemented in treatment of these defects with enamel matrix proteins, the past to control the progression of this condition the authors found an average 5-mm probing depth re- and to regenerate the destroyed . duction and an approximately 5-mm gain in probing Investigators have recommended surgical therapy in attachment level, which is comparable to the resuits conjunction with systemic antimicrobial therapy.^' reported in the literature.^'-^^ Although the studies are Clinical success has been reported with the use of bone not directly comparable, since the patients in previous grafts with or without antimicrobial therapy.^'-^^"^* studies were diagnosed with , the It has been suggested that the most clinically stable results of this case report suggest that patients having result occurs when Aa is eliminated.^' Scaling and root LAP may heal in a similar fashion as patients having planing alone has been found to be unsuccessful in the chronic periodontitis. It should be stressed that this eradication of Aa from the periodontai pocket, which particular patient was placed in a very strict plaque- has been suggested to be due to the tissue penetration control program with periodontai maintenance visits by b acted a, •'^••'^ Most investigators have used antimi- every 2 weeks for the initial 6 months after periodon- crobial therapy to assist in complete removal of these tai surgeries. This maintenance program is not sub- bacteria. While Lindhe and Liljenberg^' used tetracy- stantially different from the maintenance program uti- cline (1 g/day for 14 days) in conjunction with surgery, lized in the clinicai trials for the enamel matrix protein Mandell and Socransky^' found success with doxycy- product,'" The treatment of intrabony defects with cline (200 mg during the first day, followed by 100 enamel matrix proteins in patients with LAP repre- mg/day for 14 days) in conjunction with surgery, sents a reasonable alternative to otber periodontai re- Novak et al'''' reported effective initial control of early generative therapies. Small and narrow, three-walled LAP with systemic tetracycline therapy (1 g/day) for 6 defects respond very favorably to surgical therapy." weeks combined with supragingival plaque control. In The vertical bony defects in this case were large and 1991, Novak et al*' reported long-term (1 to 4 years} therefore less favorable to respond positively. clinical and radiographie improvement in four subjects following previously mentioned treatment regimen. The use of enamel matrix proteins in these patients CONCLUSION represents a new approach to the goal of regenerating lost periodontai tissues. The enamel matrix protein It can be concluded that the use of enamel matrix pro- product is composed principally of amelogenin and re- teins, as an alternative periodontai regenerative mater- lated proteins that are derived from porcine tooth ial, was found to be successful in the treatment of one buds,'" These enamel matrix proteins may be impor- case of LAP, Clinical and radiographie parameters had tant in the development of acellular , peri- improved significantly at 6 months after the use of odontai ligament, and bone,'"'^ enamel matrix proteins. Additional case reports and There have been several reports of clinically suc- clinical trial data will be needed to further substantiate cessful usage of enamel matrix proteins in treating in- the benefits of using enamel matrix proteins as a trabony defects.'" The use of enamel matrix proteins or periodontai regenerative material in LAP patients. guided tissue regeneration techniques to treat intra- bony defects has been shown to yield similar re- sults,*^'^^ Froum et aH* found the percentage of bone REFERENCES fill during re-entry after the use of enamel matrix pro- teins to be superior to that obtained with open-flap 1, Gottlieb G, The diffuse atrophy of the [in , Heden et aV in a series of cases, re- German], Z Stomat 1923;21:195, ported that 87% of sites treated with enamel matrix 2, Butler JH. A familial pattern of juvenile periodontitis (perio- proteins exhibited probing attachment gain of more dontosis), J Periodontol 1969;40:n5-n8, than 2 mm. 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Quintessence I nier national 251 Bonta et ai Dental Materials In Vivo: 43. Christersson LA, Albini B, Zambón J), Slots ), Genco RJ, Demonstration of Actinobacillus actinomycctemconiitans in Aging and Related Phenomena localized juvenile periodontitis [abstract 2561. J Dent Res 1983;62:198. Edited by George EUades, Theodore Eliades, William Brantley, and David Watts 44. Novak MJ, Poison AM, Adair SM. Tetracycline ttierapy in patients with early juvenile periodontitis, | Periodontol This comprehensive 1988;59:366-372, review brings to- 45. Novak MJ, Stamatelakys C, Adair SM, Resolution of early gether research by lesions of juvenile periodontitis with tetracytline therapy biomateriais experts alone: Long-term observations of 4 cases, J Periodontol in various fields of 1991;62:628-633. , including 46. Gestrelius S, Andersson C, LidstrÖm D, Hammarstrom L, Somerman M, In vitro studies on periodontal ligament cells orai and maxillofa- and enamel matrix derivative. J Clin Feriodontol t997;24: cial surgery, ortho- 685-692, dontics, periodon- 47. Heij) L, Heden G, Svärdström G, Östgren A. Enamel matrix tics, prosthodontics, derivative (EMDOGAIN) in th« treatment of intrabony pe- and restorative den- riodontal defects. J Clin Periodontol 1997;24:705-714. tistry. Through the 48. Frouni S), Weinberg MA, Rosenberg E, Tarnow D. A com- presentation of evi- parative study utilizing open flap debridement with and without enamel matrbt derivative in the treatment of perio- dence derived exclusively dontal intrabony defects: A 12-month re-entry study. J from in vivo studies, the mechanisms governing Periodontol 2001;72:25-34. the aging of materials placed in the oral cavity 49. Pontoriero R, Wennström J, Lindhe J The use of barrier are clarified and selective aspects of the in vivo membranes and en ame i matrix proteins in the treatment of performance of materials demonstrated. angular bone defects, A prospective controlled clinical study, J Clin Periodontol 1999;26:833-840. 296 pp (softcover): 183 illus (37 color); 50. Heden G, Wermström J, Lindhe J. Periodontal tissue alter- ISBN 0-86715-399-7; US $110 ations following Emdogain treatment of periodontal sites with angular bone defects. A series of case reports. J Clin Periodontol 1999;26:855-860. 51. Heden G. A case report study of 72 consecutive emdogain- ' Biomaterial Surface Alterations Foliowing treated intrabony periodontal defects: Clinical and radio- graphic findings after one year. Int J Periodontics Exposure to Biologic Fluid Restorative Dent 2000j20:127-139. ' Aging of Casting Alloys Used in Prosthodontics 52. Scuiean A, Donos N, Blaes A, Lauermann M, Reich E, and Restorative Dentistry Brecx M, Comparison of enamel matrix proteins and bioab- ' Ceramic Behavior Under Different Envi ron menta I sorbable membranes in the treatment of intrabony perio- and Loading Conditions dontal defects. A split-motith study, J Periodontol 1999;70: ' Characteristics of Retrieved Implants 255-262. 'Alterations of Dental Amalgam 53. Garrett S. Periodontal regeneration around natural teeth. 'Aging of Glass-lonomer Cements Ann Periodontol 1996;l:621-666. 'Degradation Mechanisms of Dental Resin Composites ' Disintegration of Orthodontic Appliances 'Characteristics of Used Orthodontic Brackets 'Orthodontic Utilities and Auxiliaries 'Endodontic Instruments and Materials 'Stainless Steel Oral and Maxillofacial Surgical Implants ' Leaching of iVletallic Ions from Plates and Screws Used in Jaw Fracture Fixation 'Sutures in the Oral Cavity • Bioactive Glass Bone-Grafting iViaterials

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