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The International Journal of Penodontics S. Restorative Dentistry

585

Use of Emdogain in the Treatment ofDeep Intrabony Defects: 12-MonthClinical Results. Histologie andRadiographic Evaluation

Renato Parodi, MD, DMDVGiovanni Liuzzo. DMDVPaolo Patrucco, DMD*VGerard Brune/, DDS***/Giorgio A. E. Santarefii, MD. DMD""A/incenza Birardi. DMD*/Bruno Gasparetto, EE**"*

The objective ofthis study was to evaluate the application of an enamel matrixderivative (Emdogain) in deep periodontal pocket therapy. Twenty-one patientspresenting intrabony and interproximal defects that could be treated with guidedtissue regeneration were selected. The inîrsbony defects were divided into deep(< 9 mm) and very deep (> 9 mm) defects. Bleeding on probing. Plaque Index,probing pocket depth, mobility index, gingival recession, probing attachmentlevel, and surgical bone level were measured at baseline. At 12 months, casesmere reexamined and indices recorded again. The mean probing depth decreasedfiom 8.1 ±2.1 mm to 3.2 ± T .5 mm; attachment level decreased from 10.4 ±2.4mmto7.0± T .8 mm, recession increased from 2.3 ± 1.4mmto3.8î 1.8mm;andsurgical bone level decreased from 9.Ó ± 1.9 mm to 7 1 ± 1.5 mm. No significantdifference was noted between bone defects with one or 2 waifs, between ioca'and generalized periodontitis, or between smokers ar^d nonsmokers. Significantstatistical difference was found, however, between deep infrabony defects andvery deep defects when attachment gain was considered. No adverse reaction tothe substance was noted. The good clinical results obtained were not confirmedby radiologie results; standardized and computerized radiographs at 12 monthsdid not rei-eai significant improi/ement. The histologie examination carried out on2 samples did not show evidence of new attachment. Further studies are neces-sary to clarify the action mechanism and to evaluate the long-term results of thismethod. {Int J Periodontics Restorative Dent 2000;20.585-595.)

'Private Practice, Genoa, Italy'*Priuate Practice, Cásale Monferrato, Italy.

"•Professor of Oral Biology, Faculty of Dentistry, Université Paul Sabatier,Toulouse, France

••"Private Practice, Milan, Italy,"""Statistical Consultant, Center of Cerebral Neurophysiology, Genoa, Italy.

Reprint requests: Dr R. Parodi, Via Fieschi 3/29, 16100 Genoa, Italy.

The final goal of periodontal therapyconsists not orily of arresting the tis-sue destruction caused by peri-odontal disease, but also of recon-structing periodontal tissues andmaintaining their health over theyears. Numerous clinical and histo-logie studies conducted on bothanimals and humans have demon-strated that guided tissue regenera-tion (GTR) permits the regenerationof new periodontal attachmentthrough the use of either reabsorb-able or nonreabsorbable mem-branes,'"-' However, GTR techniquesstill present some unresolved prob-lems: (1) a limit in the amount of re-generation achievable because ofmembrane position; (2) membranecontamination in cases of exposure'̂ ;and (3) delayed wound healing be-cause of the degradation of reab-sorbable membranes,^ Furthermore,the use of membranes requires agood degree of surgical skill and along healing period.

As a solution to these problems,the use of growth and cell differen-tiation factors has been proposed,*''^Growth factors (eg, transforminggrowth factor [JGF], platelet-derived

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growth factor [PDGF], etc) regulatecell proliferation in differentiated tis-sues. Cell differentiation factors {eg,bone morphogenet ic proteins[BMP]) initiate tissue developmentby inducing phenotypic conversionin undifferentiated mesenchymalcells. However, the possible use ofthese factors in periodontology hasyet to be confirmed by large-scaleclinical studies on humans.

Recent studies on both humansand animals have demonstrated thatthe cells of the Hertwig root sheath,which are constituents of the enamelorgan in formation, go through asecretory phase during which pro-teins (amelogenins) correlated to theformation of acellular cementum arereleased and deposited on the rootsurface. Once the cementum hasbeen deposited, mesenchymal dif-ferentiation and growth of the cellsthat will form the periodontal liga-ment and bone occur.^'"

The purpose of this study was toevaluate the clinical results obtainedat 12 months in deep one- and 2-walled interproximal defects whentreated with enamel matrix deriva-tives (Emdogain, Biofa). Radiograph-ie and histologie aspects were alsoconsidered.

Method and materials

Only patients with intraosseous in-terproximal defects that could betreated with regenerative therapywere selected for this study. Pocketswith a baseline probing depth of 5mm or more and bleeding on prob-ing after hygienic treatment were

the inclusion criteria; in addition, aradiographically identified angularosseous defect of at least 3 mm indepth and > 2 mm in width had tobe present. To simplify examinationand control, the teeth to be treatedwere located exclusively in the max-illary and mandibular anterior sex-tants (from the mesial wall of the firstpremolar to the mesial wall of thefirst premolar contra I ate rally).

The patients who participatedin the study were in good generalhealth and were not under medicaltreatment at the time. Before startingtreatment, all patients were providedwith detailed verbal and writteninformation concerning the study,and consent forms were signed. Asingle treatment was planned foreach patient. Patients were free tointerrupt the protocol at any timeand complete the therapy othenAiise.

The protocol foresaw initialpreparation through supragingivaland subgingival scaling and rootplaning followed by detailed instruc-tion in personal oral hygiene. Oneweek before the surgical phase, onlypatients who presented a baselinecomplete-mouth Plaque Index of15% or less were included in theexperimental trial. The followingbaseline clinical parameters weremeasured:

• Bleeding on probing (BOP)• Complete-mouth Plaque Index

(PI)

• Probing pocket depth (PPD),measured from the gingival mar-gin to the base of the pocket

• Mobility index (Ml; internationalclinical index, degrees I to III)"

" Gingival recession (RFC), mea-sured from the cementoenamel¡unction (CEJ) or from the inferiormargin of a restoration to thefree gingival margin

• Probing attachment level (PAL),measured from the CEJ or fromthe inferior margin of a restora-tion to the base of the pocket

• Surgical bone level (SBL), mea-sured intraoperatively from theCEJ to the deepest osseous level

All measurements concerningthe defects and the contiguous teethwere made in 6 different sites andwere carried out by one investigatorA manual periodontal probe (PGF/WGoldman Fox Williams, Hu-Friedy)was used, and all periodontal para-meters were measured to the near-est mm. For statistical reasons, onlythe deepest measurements wereconsidered. The morphology of theosseous defects was determinedintraoperatively, but no morphologicmeasurements were executed.

Periapical radiographs (KodakDF58 Ultraspeed) of treated areaswere taken with Rinn alignment de-vices that were customized withputty bites with repositioning putty.The radiographs were exposed at60 kv for 0.4 second and developedwith a standardized soaking timeand temperature (27°C) of the devel-oping acid. Diagnostic support isrecommended in the operative fol-low-up of regenerative techniquesaround both natural teeth andimplants to obtain clear, reliableimages that can supply useful clini-cal information that is highly sensi-tive and may be reused. It has

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become common practice to cus-tomize Rinn-type radiograph holdersso that intraoral test radiographsmay be standardized for use in con-trolled clinical studies.

Programs that can carry outcomputerized densitometric tests ona series of standardized radiographspermit useful information to be ob-tained from follow-ups even whenchanges are so small that the nakedeye may not be able to discriminatebetween similar bands of gray,'^Digital acquisition was carried outusing an Arcus Agfa scanner withbacklighting for transparency and a500 ppi resolution. Equalization ofgray shading between different radi-ographs, delimitation ofthe regionof interest, overlay of radiographs,and assignment of pseudo colorswere carried out by means of animage-analysis program (Image-ProSystem II, Immagini & Computer) inWindows 3.1.1 on a personal com-puter. The images were photo-graphed on Polaroid hiigh Contrastfilm with a Polaroid Palette 5000S, Inaddition, photographic documenta-tion and histologie examinations on2 cases were performed.

Baseline data

Twenty-three patients were selectedfor the study, but only 21 were in-cluded (11 men, 10 women) becauseofinsufficient plaque control (proto-col limit < 1 5%) in 2 cases. The meanage was 53 (range 41 to 70 y). In the21 patients examined, 7 smokedmore than 10 cigarettes per day,while 14werenonsmokers, Patients

were grouped into those presentinglocalized periodontitis, ie, a singledefect greater than 5 mm ¡n depthbetween 2 contiguous teeth of thesame jaw, and those presenting gen-eralized periodontitis, ie, more thanone defect greater than 5 mm indepth between 2 contiguous teethof the same jaw. At baseline, 8 pa-tients with generalized periodontitisand 13 with localized periodontitiswere present.

At the time of surgery and fol-lowing debndement, only one- andtwo-walled defects were included inthe evaluation (8 one-walled defectsand 13 two-walled defects). Themean baseline measurements areshown in Table 1,

Pockets were also grouped intodeep (between 5 and 8 mm with amean of 6.5 mm) and very deep (> 9mm with a mean of 10.2 mm).Twelve deep defects and 9 verydeep defects were present.

Surgical treatment

After local anesthesia avoiding papil-lae, a full-thickness flap was elevatedwith an intrasulcular incision made sothat papillae were preserved. Whererequired, one or 2 vertical releasingincisions were also made. After care-ful debridement of the defect andlight root planing, the root surfacewas etched for smear layer removalfollowing the manufacturer's instruc-tions using orthophosphoric acid (15s) for the first cases and ethylenedi-aminetetraacetic acid (EDTA) for allother cases. Following rinsing withsaline solution, a vial of Emdogain

that had been prepared 20 minutesearlier was applied to the exposedroot. Starting from the deepest siteof the defect, the gel was carefullyapplied. Flaps were closed andsutured to obtain primary closure.Additional Emdogain was appliedunder the closed flaps to compen-sate for material lost dunng suturing.No periodontal dressing was ap-plied.

All patients were put on bacam-picillin (2,400 mg/day) and flur-biprofen (100 mg/day) until sutureremoval 2 weeks after surgery. Pa-tients were instructed to rinse dailywith 0,2% chlorhexidine and to avoidthe use of dental floss for the firstmonth following surgery. Profes-sional hygiene was performedmonthly for 12 months.

Results

C//n/ca/ results at 12 months

In spite ofclinical control, 2 ofthe 23cases initially selected for the studycould not be included in the finalevaluation because plaque levelswere superior to the parameters setby the protocol, and at the final ex-amination their clinical parameterswere identical to or worse than thoseat baseline. In all other cases, the PIwas maintained within the study lim-its (< 1 5%) during the whole obser-vation penod.

Clinical healing was obtainedwithout complication in all but 2cases where plaque, marginal inflam-mation, and bleeding were presentat the second examination (30 days).


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Mean values and standard deviations of studyparameters (mm)

PPDRECPALSBL

Initial

8.09 ±2.122.29 ±1.38

10,38 ±2.389.61 ± 1.90

12 mo

3.19 ±1.473.76 ±1.766.95 ±1.837.08 ±1-55

Change

4.9-1.473.432,54

Student's f test*

10-16-5.259.646.08

"P< 00001.PPD = probing pocket depth from gingival margin to base of pocket: REC = gingival recession IromCEJ or inferior margin of a restoration to base ofpocket; PAL = distance from CEJ or inferior margin ola restoration to baseofpocket;SBL = surgical bone level.

Table 2 Mean values and standard deviations of studyparameters by type of defect (mm)

Localized sitesPPDRECPAL

Generaiized sitesPPDRECPAL

One-walled defectsPPDRECPAL

Two-walled defectsPPDRECPAL

Deep defectsPPDRECPAL

Very deep defectsPPDRECPAL

Initial

8.31 ±2,462.54 ±1.61

10,85 ±2-73

7,75 ± 1-491.88 ±0.849,63 ±1-51

8,25 ±2.122.38±1.19

10-63 ±2.50

8.00 ±2.202.23 ±1.54

10.23 ±2.39

6.50 ± 0.802-25 ± 1.608.75 ± 1.49

10.22 ±!.302.33±1.12

12,56 ±1.33

12 mo

3.31 ±1.654.39 ±1.857,69 ± 1,75

3.00 ±1.202.75 ±1-045.75 ±1.28

2.63 ±1.304.38 ±2.137.00 ±1.85

3.54 ±1.503.38 ±1.456.92 ± 1.89

3.08 ±1.383.08 ±1.386-17±1.19

3.33 ±1.664.67 ±1.878.00 ± 2,06

Change

5.00-1.853.15

4,75-0.88

3.88

5.63-2.00

3.6B

4,46-1.15

3.31

3.42-0,83

2.58

6-89-2.334.56

Student'srtest

7.57*4.55*7.77"

6,54*-3.86"'

5.81»

5.96*-3.53^

6-81*

8.68*-4,21*6.8T

9-54*-3.46+6.20"

13.45"-5.29*12.09-*

"P< 0.0001.|p<o.oi.' P < 0 001.PPD = prot)ing pocket depth from gingival margin to ba5e of pocket: REC = gingival recession fromŒJorinferiormarginofarestoration to base of pocket: PAL ^distance from CEJ or infenor margin ofa restoration to base of pocket.

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Treatment with metronidazol-ben-zoate gel (Elyzol-Dumex Alpharma)was carried out, and the patientswere remotivated in oral hygiene.After this treatment, there was a re-turn to a normal clinical profile. Fiveofthe21 patients were supplied withan extracoronal dental splint toreduce mobility [Ribbond Reinforce-ment).

Twelve months after surgery allcases were reexamined; parameterswere measured again and radi-ographie checks were performed. Atthe final checkup no case presentedbleeding on probing, and plaqueremained within the limits estab-lished by the initial protocol. Thegingiva appeared clinically healthyand normal in both architecture andcolor Dental mobility was reduced inmost cases by an average of onedegree.

Atthe beginning ofthe study, allpatients had accepted a small reen-try limited to the single test tooth toverify healing, but 8 patients did notaccept reentry after data collection.Surgical reentry was performed in 13cases. In all reentry cases, the defects[checked with 4.5x magnification)appeared remodeled and their mor-phology differed from baseline: inthe cases where attachment gain hadbeen obtained, there was a new,thick, white tissue that was rubberyin consistency, well adherent to thesurfaces beneath, and difficult toprobe. At this time, the structure ofthis new tissue was not similar to theosseous tissue surrounding it.

Data at Î 2 months

At the end of the trial period (12 mo),the PPD, PAL, and REC values wereanalyzed. The other indices wererecorded but not evaluated statisti-cally. The measurements taken(baseline and control) were analyzedthrough the Student's ttest for pairedsamples and showed differences thatwere statistically significant.

For the 21 patients considered,the mean PPD was reduced by 4.9 ±1.0 mm. Mean PAL gained 3.4 mm.The mean REC increase was 1.5 mm[Table 1).

The patients were split into sub-groups to test the frequency of otherfactors affecting the final results. PALgain differences between men andwomen (3.45 mm vs 3.4Ö mm) wereevaluated but were not statisticallysignificant. There was no statisticallysignificant PAL difference (3,5 mmvs 3.3 mm) between smokers andnonsmokers.

A slight difference in attach-ment gain between localized [PAL3.2 mm) and generalized (PAL 3.9mm) periodontitis sites and be-tween one-walled [PAL 3.6 mm) and2-walled (PAL 3.3 mm) defects wasfound. On the other hand, there wasa greater REC difference betweenone-walled (REC 2.0 mm) and 2-walled (REC 1.1 mm) defects. Ahighly significant difference was pre-sent between deep defects (< 9mm) and very deep defects [> 9mm). In deep defects [mean depth6.5 mm), the gain was 3.4 mm forPPD and 2.6 mm for PAL, whereasfor very deep defects (mean depth10.2 mm), the gain was 6.9 mm for

PPD and 4.6 mm for PAL. Fourrecessions [44%) greater than 3 mmwere recorded in the very deepdefects group; recession occurredonly once (8%) in the deep defectsgroup [Table 2). In the 13 caseswhere surgical reentry was permit-ted, the mean SBLgain was 2.5 mm[Table 1); in these same cases themean PAL gain was 3.7 mm.

Two clinical cases at baselineand after 12 months are presentedin Figs 1 and 2. Good clinical resultswere noted atthe end of treatment,whereas no significant improve-ment was evident from a radiologiepoint of view. In fact, when com-paring the initial radiographs withthose taken at later examinationsup to 1 year after surgery with theuse of Emdogain, there were nosignificant differences regarding theinterdental bone profile and its den-sity in the treated areas. Both on theoriginal radiographs and on thecopies processed with computer-ized densitometry, the operatedareas showed minimal variationwhen compared to initial condi-tions. These modest differences,which were even found to be neg-ative in 2 cases, may be because ofmistakes in technique.


590

Fig l a (ieft¡ One-vtalled defect distal ofmandibular left lateral indoor. Surgicalprobing tiers is M mm.

Fig 1b (nght) Surgical reentry.Remodeling of bone defect is euidenl withe'imination of intrabony defecl.

Fig 1c ¡left) Left, standardized preopera-tive radiograph. Right, standardized radi-ograph at surgical reentry

Fig Id (right) Left, initial raciiographunder computerized snafysis. Right, inter-dental septum at 12 months. There is mmi-mal variation m profile and density distallyat mandibuiaf Jeft lateral incisor.

Fig 2a Pocfeet exposure of mandibular leftlateral incisor measured 6 mm on initialprobing. Intraoperatively, defect is identifiedas one walJed witii probing depth of 9 mm.

Fig Zb Defect is filled with Emdogain. Fig 2c Oiie-mm probing depth and 3-mm gingival recesssion before surgicalreenliy al 12 months.

Fig 2d ffeenlry after 12 months showspartial fill of the defect-

fig 2e Left, standardized presijrgicsfradiograph of lateral incisor Right, radi-ograph at 12 months.

Fig 2f Left, iniiiaf radiograph of lateralincisor under computerized analysis. Right,there is iiltle difference between this radi-ograph 02 mo) and the initial one.Interdental septum shoivs moderateincrease in mineralization level


591

Fig 3a General view. The root shows evi-dence of scaling. The continuity betweenteetfi and periodontal tissue fs rather badlymaintained Arrow = apical notch. (Originalmagnification X 16; light green stain J

Fig 3b Higher magnification of upperbox in Fig 3a. The surface of the roolshows signs of résorption and is occupiedby mu/iinudear cells (A). (Onginal magnifi-cation X TOO, light green stain )

Fig 3c Higher magnification of louver bo«in Fjg 3a. Connective tissue adheres noi-maiiy to the root, bu! there is no cemen-tum apposition on the planed surface. Asmall amount of newly formed bone(arrow] occupies the notch. (Original mag-nification X 160; Jightgreen stain.)

Histology

Histologie tests were carried out byblocksection on 2 patients who werenot included in the clinical testing.Extraction of these teeth was plan-ned because of advanced loss ofsupporting structures. The attach-ment level around these teeth was< 15% of the total, and the defectswere one or 2 walled. After obtain-ing signed and informed consent,the teeth were treated with the fol-lowing protocol. To serve as a refer-ence point at surgery, a notch was

made with a 'Á round bur on the rootsurface at the bottom of the bonedefect. The teeth were extractedafter 6 to 9 months by means ofreduced block section. The extrac-tion wounds were filled with allo-plastic material and sutured.

The tooth and the surroundingtissues were fixed in 10% neutralbuffered formalin solution, dehy-drated with ethanol containing 0.3%basic fuchsin, and embedded inmethyl methacrylate. The blockswere sectioned mesiodistally with aband saw and subsequently ground

to a thickness of 30 \im. Ground sec-tions were stained in light green.Histomorphometric analysis was per-formed in blind trials on 2 sections ofeach block using a video camera onthe microscope coupled with animage-analysis system.

Histology as performed on the 2specimens showed only slight re-generation. Continuity between theroot and supporting areas was re-established only at the most apicallevel ofthe notch. A slight amount ofnew bone was seen, but there wasno new cementum formation {Fig 3).


592

Discussion

One of the fundamental rules in evi-dence-based medicine for evalua-tion of new treatment efficacy is theuse of only randomized controlledtrials and the meta-analysis of morecontrolled trials done on the sametreatment. To date, scientific evi-dence shows that the treatment ofinfraosseous bony defects with tra-ditional periodontal surgery andGTR techniques allows a certain typeand percentage of healing in one-and 2-walled defects. A comparisonofthe results obtained using differ-ent techniques is possible only if thesame type of defect in the samepatient is treated in a significantnumber of cases.

First, it is important to underlinethat the regenerative process in-duced by enamel matrix derivativesis quite different from that obtainedwith GTR. When using the GTR tech-nique, healing is obtained by meansof (T) clot protection, ('2) use of a bar-rier that allows the deep periodon-tium cells to reproduce without inter-ference from the superficialperiodontium, and (3) empty spacebetween membrane and underlyingtissues that allows the new tissue togrow within the defect. These ruleshave little significance when usingEmdogain because this producttheoretically reproduces a morpho-genetic process that occurs in natureat the time of development of thedental organ. This fact affects boththe type and timing of healing.

The purpose of this study was toevaluate the efficacy of Emdogain inthe treatment of infrabony defects in

humans. However, the number ofpatients examined in this study wasnot sufficient to draw definitiveconclusions on this new material.Nonetheless, significant data thatprovide useful indications have beenobtained. First, no adverse clinicalreactions were observed, similar tothe findings of Zatterstrom et al,'^The data obtained clearly indicatethat this material significantly im-proves baseline clinical parametersat 12 months. The mean reduction inprobing depth (4.9 mm) and themean attachment gain (3,4 mm) aresimilar to other values obtained withGTR using reabsorbable and nonre-absorbable membranes'^" with orwithout grafts,'^'•^'' However, it isimportant to note the significant dif-ferences in the results when the dataare analyzed according to the initialdepth of the defect. In deep defects(5 to 8 mm) the mean reduction inPPD was 3,4 mm versus 6,9 mm forvery deep defects (> 9 mm). Theattachment gain for deep defectswas 2.6 mm versus 4.5 mm for verydeep defects. This clinical study didnot have control sites. The test siteswere clinically and radiographicallyreexamined after 1 year

Our results agree with previousstudies demonstrating that pocketreduction and attachment gaindepends on the initial depth of thedefect, both in conventional sur-ggryíi.í? gnd with GTR using eithernonreabsorbable^^"^^ or reabsorb-able membranes.'"'^* At the time ofthis writing, only a few papers werefound in the literature'-''^'"^" on theregenerative potential of Emdogainfor the treatment of periodontal


593

defects. In a group of 107 patientswith a mean initial PPD of 7.4 mm,Zatterstrom et al'^ obtained a meanPPD reduction of 4.3 mm at 8 and 16months, and 3.8 mm at 36 montfis;and a mean PALgainof 3.1 mm at 8months, 3.3 mm at 16 months, and2.9 mm at 36 months. In a compar-ative study between Emdogain andmodif ied Widman flap on 33patients with predominantly 2-walled defects bilaterally and with amean initial PPD of 7.8 mm, HeijI etal^' obtained a mean PPD reductionof 3.3 mm at 8 and 16 months and3-1 mm at 36 months; mean PALgain was 2-1 mm at 8 months, 2.3mm at 16 months, and 2.2 mm at 36months in sites treated with Emdo-gain. In control sites treated withmodified Widman flap, the meanreduction in PPD was 2.6 mm andthe mean PAL gain 1.7 mm at 16months {P < 0.05). Recently, Sculeanet al^^ compared the resultsobtained with randomly assignedtreatment either with Emdogain orGTRwith reabsorbable membranesin 16 patients with 2 symmetricinfraosseous defects. In the defectstreated with Emdogain, a reductionfrom a mean initial PPD of 8.1 mm to4.3 mm was obtained; there was aPAL gain of 3.1 mm and an increasein REC of 0-8 mm. After 9 months,none of the parameters examinedrevealed statistically significant dif-ferences between the 2 treatments.It should be noted, however, thatmost of the defects treated in thisstudy were 2- and 3-walled defects.

In our study it is interesting tonote recession behavior. Even if themean REC value [1.48 mm) is

comparable to those of other stud-jes_i4,24,2E ̂ he increase in mean RECdoubled in one-walled (REC 2 mm)compared to 2-walled defects (REC1.1 mm)- Furthermore, 5 ofthe 21patients (23%) showed recessions> 3 mm; considering the fact that weoperated in the anterior sextant, thisis a noteworthy complication. Thismay be explained by the fact that,without support provided by existingosseous walls, a membrane, or afiller, soft tissues may collapse. Fromthis pointofview, a filler may be use-ful. On the other hand, with the useof Emdogain, barriers and fillers arenot needed, and therefore neithercomplications nor limitations inattachment gain caused by the pres-ence and position of a membrane orfillers are possible.

In our study we did not observea statistically significant difference inattachment gain depending onsmoking habit-*' or defect morphol-ogy

In this study optimal plaque con-trol through clinical supervision waspart ofthe protocol. The 2 patientsexcluded from the study because ofhigh plaque levels did not show anyimprovement after treatment.

All measurements in this studywere manually performed, and thusdata may not be completely reli-abte-*̂ because of the many variablesrelated to probing. A clinical triaP^has demonstrated that tooth mobil-ity positively influences probinglevel. Moreover, all teeth with > 9mm pockets presented an initialmobility of degree I or II. At the endof treatment, mobility was reducedwith respect to baseline.

To date, the amount of timerequired before considering the GTRregenerative process complete is stilldebated. Through imitation of nor-mal tissue development, the use ofenamel-derived proteins (Emdogain)is an alternative approach to peri-odontal regeneration. HeijI et aP'demonstrated continuous clinicalimprovement over 3 years from ini-tial surgery. On the other hand, inour study at 12 months, no signifi-cant improvement in radiographiebone level was detected; in surgicalreentry cases at 12 months, wefound a new tissue that had a rub-bery consistency, was well adherent,and could not be probed but wasnot mineralized. However, it is worthnoting that in HeijI et al's study,^' themean radiographie gam at 8 monthswas limited to 12% of initial boneloss, 32% at 16 months, and 36%after 3 years. In Zatterstrom et al'sstudy,'^ the radiographie gain was15% at 8 months and 31% at 36months. Some studies on hu-mans'^'^'''^^ demonstrated that com-plete bone remineralization cannotbe expected before 1 year. Ourresults may have differed with ananalysis after a longer period.

The difference between our his-tologie results and those of otherstudies is more difficult to explain-Hammarstrom et al ' found almostcomplete regeneration of acellularcementum, well attached to thedentin and with new fibrous attach-ment, in an experimental model ofdehiscences in monkeys treatedwith enamel matrix derivatives. Asimilar result in a defect model ofsimilar type was obtained by Heijl^'


594

in humans. Araujo and Lindhe^treated degree III furcations withEmdogain and reabsorbable mem-branes in an expenmental study ondogs; a thin layer of acellular cementwas observed in the most apical partof the defect, whereas the crownarea presented a thick layer of cel-lular cement. It is true, however, thatthe above histology regarded ex-perimental sites and did not repre-sent the true situation of periodon-tal disease. Recently, in a case reporton humans, Mellonig treated a one-walled defect with Emdogain.-^^After 6 months there was an attach-ment gain of 4 mm, a reduction inPPD of 5 mm, and limited radi-ographie gain. In the histologieexamination of a block section, re-generation of new attachment con-sisting of new bone, new ligament,and new acellular cementum wasfound. It must be noted, though,that the tooth concerned had beenextracted for prosthodontic and notperiodontal reasons. In our studylimited to only 2 block sections, nonew cementum or fibrous attach-ment was found, but only slight for-mation of new bone. It is true, how-ever, that Melionig's histologieexaminations did not regard a caseof advanced periodontal disease,whereas in our case, the teeth con-cerned were scheduled for extrac-tion because of very advanced peri-odontal disease. The rather limitedlevel of residual per iodont ium(< 15%) may have negatively influ-enced the regeneration process.

However, this difference in re-sults, especially from a radiographieand histologie point of view, shows

the need for new controlled studiesto verify whether the regeneration ofperiodontal attachment is a com-mon or episodic finding after treat-ment with Emdogain and whetherradiographie gain is related to thetype of defect or is a function of time.

Conclusions

The following conclusions may bedrawn:

1. The material used in this studyshowed high biocompatibility

2. Its use resulted in a good reduc-tion of probing depth and gain inclinical attachment.

3. Its effectiveness was greater inthe presence of deeper initialdefects.

4. No significant improvement wasnoted after 1 year in control radi-ographs.

5. The histologie specimens did notconfirm the formation of new fi-brous attachment or new eemen-tum.

Acknowledgment

The authors would like to acknowledge DrVarían Gianighian, Biora Italia Director, for hisassistance and kindness.

References

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2. GottlowJ, Nyman 5, Karring T, LindheJNew attachment as the result of con-trolled tissue regeneration. J ClinPeriodontol 1934;11:494-503.

3. Stahl S, Froum S, Tarnow D. Human his-tologie responses to guided tissue regen-erative techniques in mtrabony lesions:Case reports or 9 sites. J Clin Penodonîol199O;17 191-199.

4. Tonetti MS, PiniPrato G, Cortellini PFactors affecting the heaiing response ofmtrabony defects following guided tis-sue regeneration and access flap surgery.J Clin Periodontol 1996;23:548-556.

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