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Critical Reviews in Oral Biology & Medicinehttp://cro.sagepub.com/

Autogenous and Allogeneic Bone Grafts in Periodontal Therapy

James T. MellonigCROBM1992 3: 333DOI: 10.1177/10454411920030040201

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What is This?

CriticalReviews inOralBiologyandMedicine, 3(4):333-352 (1992)

AutogenousandAllogeneic BoneGrafts in

Periodontal TherapyJames T.Mellonig, D.D.S., M.S.

DepartmentofPeriodontics,TheUniversityofTexas,HealthScienceCenter,SanAntonio,TX 78284

ABSTRACT: This article is limited to a review ofbone autografts and allografts, as used inperiodontaltherapy. The various graft materials are discussed with respect to case reports, controlled clinical trials,

and human histology.Otherreviewedareasarewoundhealingwithperiodontalbonegrafts, tissuebankingand

freeze-dried boneallografts, and theuseofbonegrafts inguided tissue regeneration.

KEY WORDS:Periodontal,boneautograft,bone allograft, tissuebanking, guided tissue regeneration.
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I. INTRODUCTION

Bacterially inducedperiodontitis leads to the destruction of tooth-supporting tissues, culmi-

nating in tooth loss. Disease reversal with regeneration of new bone, cementum, and perio-dontal ligament about a root surfacepreviously contaminatedbybacterialplaque istheultimate goalofperiodontal therapy.

Bonegrafts,bothautogenousandallogeneic, are feltby some tobeessential if restoration of lostbone accompaniedby a functional attach- mentapparatusistobeachieved. "Bone grafting materials

will enhance regeneration of anew attachment apparatus" (Bowers et aL, 1989c). "Osseousgrafting therapyhasbeenshowntobe clinically successful fortimeintervalsexceeding

20yearswhenencompassed inacomprehensive careprogrambasedoneffectivedailyplaquecon- trolbythepatientandaprofessionally supervised periodontal maintenanceprogram" (Schallhorn,1980).

Othersbelieve that the use ofbone grafts to enhance regeneration of theperiodontium is un-

acceptable. ''Notoneofthehumanimplantstud- ieshasprovided the typeofexperimental model thatclearly demonstrates new attachment for-

mation. Manyof theinvestigatorshavefailed toprovide controls, and none haveprovided the unequivocal histologic evidence of new attach- mentto previously diseased roots" (Gara and Adams, 1981). "From the standpoint of scien- tificdocumentation, the value (of regenerative procedures) is not clear. Spectacular results of "bonefill" in intrabonypockets havebeen reported with or without bone implantation" (Ramfjord,1984).

Stillothersareconvinced thatbonegrafts are detrimental. "Ignorance of the contribution of thevarious tissue components in periodontal wound healing may explain the widespread use ofbonetransplants in the treatmentof intrabony pockets" (Karing et aL, 1984). "Since granulation tissuederived from bone has thepotential to induce root resorption and ankylosis, the rationale offavoringbone growth with theuseof bonetransplantsishighlyquestionable" (Karring etaL, 1980).

Clinicalcasereports,controlledclinicaltrials, andhumanhistologydocumenting theresultswith bonegrafts havebeen reviewedpreviously (Pfei- fer, 1969; Groff, 1976a and b; Ellegaard, 1976;Schallhorn, 1977; Schallhorn, 1980; Mellonig,1980; Wirthlin, 1981;Gara and Adams, 1981;

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Bowers et ai, 1982; Pierce, 1982; Diaz-Arnold andZach, 1985;Gonsalez, 1986;Mellonig, 1986;Yazdi and Schonfeld, 1987; Egelberg, 1987; Krejci and Farah, 1987; Wiseman and Tene-

baum, 1988;Hancock, 1989;Mellonig andBow- ers, 1990; Mellonig, 1991). Thepurpose of this

article is to evaluate the literature in an attempt to clarify the current state of the art of regener-

ation withperiodontalbonegraft therapy.

II. TERMINOLOGY

The definitions provided here are adapted from theAmerican Academy of Periodontology'sGlossary ofPeriodontic Terms.

Regeneration is the reproduction or recon- stitution of a lost or injured part. As applied toperiodontics, itmeans the formation ofnewbone, cementum, and periodontal ligament on a pre-

viously diseased root surface.

At one time the terms regeneration and new attachment were synonymous. Today, new at-tachment means the reunion of connective tissue with a root surface that hasbeen deprived of itsperiodontal ligament. This reunion occursby the formation of new cementum with inserting col-

lagen fibers. The formation of new bone is not necessarily a condition of new attachment. In

addition, new attachment to a root surface may be mediated through epithelial adhesion (junc-

tionalepithelium)orconnective tissueadhesion.

Likewise, in thepast, the terms newattach- ment and reattachment were often used inter-changeably.Reattachmentmeanstoattachagain, thereunion ofconnective tissuewitharoot sur- faceonwhichviableperiodontal tissue ispresent. The area of reattachment is not affected bybac- terial

contamination.

Attachment apparatus refers to the cementum, the alveolar bone, and the periodontalligament.

Repair is the healing of a wound by tissue thatdoesnotfully restorethearchitectureorfunc-tionof thepart.

Bonefill is thepresence of hard tissue in a periodontal osseous defect, as determined byclinical re-entry of the original defect site. This termdoesnot indicate thenatureofthehistologic

attachment tothetooth. Theamountofbone fill

is usually determined by surgical reentry procedures.

Intraosseous (intrabony) refers to aperio- dontal defect withinbone.An autograft is a tissue graft (bone) trans- ferred from oneposition toanewposition in the

same individual.

An allograft (homograft) is a tissue graft (bone)between individuals of the same species butwith nonidentical genetic composition.

Axenograft (heterograft) isatissuegraftbe- tween members of different species.

III.PERIODONTAL BONEGRAFTS: HISTORICAL PERSPECTIVE

The use ofbone grafts inperiodontal therapy canbe traced to the work of Hegedus (1923). He

reported success in six casesby transplanting autogenous bone from the tibia to thejaws to treat

"advancedpyorrhea". Subsequent tothis report and for the next several decades, the evaluation of

xenografts of various typesbecame themain focus of attention.

Buebe and Silvers (1936) usedboiled cow bonepowder tosuccessfully repairintrabonyde- fects

in humans. Studies in dogs (Beube, 1934 and 1942) suggested that surgically createdper- iodontal

defects hadanaccelerated rateofhealing afterplacement ofboiled cowbonepowder, with boneand

cementumbeingdepositedmorerapidly ingrafted defects.

Ospurum is oxbone that is soaked inpo- tassiumhydroxidetoremovecollagen,inacetone to

remove lipid,and inasaltsolution toremove proteins. Forsberg (1956) used this material in

11human intrabonydefects. Oneshowedexcel- lent results, seven were satisfactory, and three were

unsatisfactory.

Anorganic bone is bovine bone from which the organic material is extracted by means of

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ethylenediamine and autoclaved. Melcher (1962) grafted 187bone defects in 163patients with a

minimum follow-up of3years.Hefelt thatpro- tracted sequestration and slow resorbtion miti- gated

against the use of anorganicbone. Patur andGlickman (1962) found similar results.

Boplant isbovinebone that ispreparedby detergent extraction, chloroform methanol ex-

334

traction to reduce lipid content, sterilization in propiolactone, and freeze drying. In 77 intraos-

seous defects in 56patients, Scopp etal (1966) reported pocket depth reduction of 3 mm at 6monthsandanadditionalmillimeterafter 1year. Older (1967) reportedgood results infour cases, fairresults in three, and unsuccessful results in two, as measuredbyprobing depth reduction and

increasing radiographic density. The widespread clinical use that followed these reports resulted in

routinerejection andfailure (Emmings,1974). Boplant was subsequently withdrawn from the market

(Emmings, 1974).

IV. CASE REPORTS AND CONTROLLED CLINICAL TRIALS WITH AUTOGENOUS AND

ALLOGENEIC BONEGRAFTS

Case reports document the clinical success or failure of a therapeuticprocedure,provide in-

formationontechniquesensitivity,andmaystim- ulate research intothevalidity of theprocedure. They

have scientific value only when a large number of cases are reported andbecome anec- dotalwhen published as isolated procedures. In addition, the repeatability of results, as reported by a

significant number of investigators, lends credence toclinicalpredictability. Becauseearly bonegraft

literature wasconcerned mainly with clinical feasibility and technique, comparisons withprocedures

that have the same or similar objectives were not accomplished. It was only later that controlled

clinical trials were felt tobe necessary, as several authors speculated that an equivalent amount of

bonefill couldbeachieved irrespective of whether theprocedure included a bonegraft (Roslingetal.,1976;Ellegaardetal.,1971; Poison and Heijle, 1978). In addition, as judged by present-day standards, many of the

early controlled studies were inadequately de- signedbecause thepatient did not serve as the unit

ofcontrol(Hujoeletal., 1990).Yetacritical analysis of these studies revealed that in no in- stancewas the controlprocedure (open flap debridement)tobesuperiortothebonegraft (Table1).

A.Autogenous BoneGrafts

There are several types of autogenousbone

grafts thathavebeenor arebeingused clinically. They include cortical bone chips, osseous coa-

gulum,boneblend, intraoral and extraoral cancellousbone, and marrow.

1.CorticalBoneChips

The impetus for the modern-day use ofperiodontalbone grafts canbe traced to the workof

Nabers and O'Leary (1965). They reported that shavingsofcorticalbone removedbyhandchis- els

during osteoplasty and ostectomy from sites within the surgical area couldbe used successfully to

effect acoronal increase inboneheight. The intraosseousdefects sotreatedwereprimar- ily one- and

two-walled and not felt by the authors tobe amenable to other methods of treatment.

Subsequently, Nabers reported long-term success with 18- to 24-monthposttreatment clinical

documentation for sixcases (Nabers, 1984). Although there is apaucity of information with respect

tocorticalbonechips, amore recentpub- lication suggests that this type of graft is still in use and

may result inbone fill with decreased probing depth (Langer et al, 1986). Cortical chips, due totheir relatively largeparticle size

1,559.6 x 183fxm(ZayerandYukna, 1983)andpotentialforsequestration,werereplaced byautogenousosseouscoagulumandboneblend.

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2.OsseousCoagulumandBoneBlend

Intra-oralbone, when obtained with high- or low-speed roundburs and mixed withblood,be-

comes a coagulum (Robinson, 1969;Jacobs and Rosenberg, 1984). The rationale for the use of

osseous coagulum is the belief that the smaller the particle size of the donor bone, the more

certain its resorption and replacement with host bone (Robinson, 1969). It was subsequently

demonstrated in monkeys that small boneparti- cles of 100 |xm could provide for earlier and

greaterosteogenicactivity thanparticlestentimes as large (Rivault etal, 1971).The bone blend technique was designed to overcome some of the disadvantages of osseouscoagulum, including inability to aspirate during the collection process, unknown quantity and

335

TABLE1HumanControlledStudieswithBoneAutograftsandAllografts inthe

Treatment of Periodontal Osseous Defects

Graft material

Methodof evaluation

GraftMean iesults

Control

Ref.

ICBMProbingand

radiographsEqualdegreeofsuccessEllegaardand

Loe(1971)

OC-BB ECBM

ICBM ICMB ICBM

Reentry

Probing

Probingand

X-rays Probingbone level

2.98mm

(7 1%bonefill)4.36mm

(6 1% fill)

3.07 mm (2-wall)

2.35mm (1-wall)

3.2mmgain attachment

1.2 mmgain (significantonly fordeepest defects)

0.66mm

(22%fill)

2.15 mm(2-wall)

2.25mm(1-wall)

2.0mmgain attachment0.8mm

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Froumetal. (1976)

Carraroetal. (1976)

Movinetal. (1982) Renvertetal. (1985)

ICBM ECBM

Reentry

Nosignificant difference

Graft improved resultsof treatmentPatur(1974)

ICBMECBM CBMA ICBM CBMA

CBMA CBMA

FDBAHistology

Histology

Reentry and probingbone Reentry

ReentryRegeneration

consistently found

Newboneand cementum

4.83mmfill

1.6 mm

(54%bonefill)

60%defects

>50% bonefillLackofcemento-

genesisand bone formation Little ifanynew cementumor bone

0.22 mmfill

0.8mm

(33%bonefill)

60%defects

>50% fillHiattetal.

(1978)

Listgartenand Rosenberg (1979)Hiattetal.

(1986) Schradand Tussing (1985) Altiereetal. (1979)FDBA

HistologyNewattachmentgreater ingrafted

sitesMoomaw

(1978)

FDBA

FDBA

+

TCN DFDBAReentry

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X-ray1.9 mm(39%fill)

2.8mm(61%fill)

1.38 mmfill1.0 mm(31%fill)

1.4 mm(36%fill)

0.3mmfillMabryetal.

(1985)

Pearsonetal. (1981)DFDBA

HistologyNodifference inhealingDragooand

Kaldahl

(1983)DFDBA

Reentry2.57mm

(65%bonefill)

1.26 mm

(38%fill)Mellonig (1984)

DFDBA DFDBA

Reentry

Histology

Nodifference betweendefects treated withandwithoutIDonegrafts Regeneration inbothgraftedand

nongraftedsites inthesubmerged

environment;greaterandmorefre- quent regeneration ingraftedsitesSantesetal. (1988) Bowersetal.

(1989b)

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DFDBA DFDBA

Histology

Reentry

New bone,cementum, PDL

2.60 mm bonefi

No new attachment apparatus

0.38 mm bone fill

Bowers etal. (1989c) Blumenthal and Steinberg

(1990)

OC-BB ICBM ECBM CBMA FDBA FDBA+ TCN DFDBA= Osseous coagulum-bone-blend autograft.

= Intraoral cancellous bone and marrow autograft.

= Extraoral (iliac) cancellous bone and marrow autograft.

= Cancellous bone and marrow allograft.

= Freeze-dried bone allograft.

= Freeze-dried bone allograft plus tetracycline.

= Decalcified freeze-dried bone allograft.

= Significant difference infavor of bone grafting.

qualityofcollectedbonefragments, and fluidityof thematerial (Diemetal, 1972).Boneblend is cortical or cancellousbone that isprocured with

a trephine or rongeurs,placed in anamal- gamcapsule,andtriturated totheconsistencyofaslushyosseousmass.Theresultantparticlesize is in the range of 210 x 105 |xm (Zayer andYukna, 1983).Casereportsindicatethatintraos- seousdefects canbe successfully managed with this

graft material (Robinson, 1969). A mean bone fill of 73% was obtained in 25 defects (Froumet al, 1975). Froum et al (1976) reported the osseous coagulum-bone-blend typeof graftsprovided 2.98 mm coronal growth of alveolar bone, compared with 0.66 mm obtained when

open flap debridement alonewasused.

3.IntraoralCancellousBoneand

Marrow

Healing bony wounds, healing extraction sockets, edentulous ridges, mandibular retro-molar areas, and the maxillary tuberosity have all been used as sources of intraoral cancellousbone and marrow (Hiatt and Schallhorn, 1973; RossandCohen, 1968;Soehren andVonSwol,1979; Halliday, 1969; Rosenberg, 1971). Bone fill in all types of intraosseous and furcation de-fects has been demonstrated with this material (Hiatt and Schallhorn, 1973; Soehren and Von

Swol, 1979;Halliday, 1969;Rosenberg, 1971). Ameanbone fill of3.65 mm, withup to 12mm insome lesions, and >50%bone fill on apre- dictable basis have been achieved (Hiatt and

Schallhorn, 1973;Rosenberg, 1971).Inaneval-

uation of 191 defects in 91 subjects, Ellegaard and Loe (1971) reported that grafts of intraoral

cancellousbone and marrow did not appear to influence the clinical outcome when compared withsurgical curettage. Likewise, Renvert et al. (1985) found limited differences between grafted andnongrafted sites. They did, however, note significant differences in favor of grafted sites whenonly the deepest defects were compared and suggested that intraoral grafts be limited to treatingdeep lesions. Asdeterminedbyprobing depthmeasurements,Carrraroetal.(1976)found nodifferencein the responsebetweengrafted and nongrafted one-walled defects. Two-walled defects respondedmore favorably whengrafted than ungrafted controls. Also, Movin et al. (1982) reported a3.2-mmgain inclinicalattachmentin grafteddefectsand2.0mminnongrafted defects.

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4.Extra-oralCancellousBoneandMarrow

It is generally agreed that the extraoral cancellous bone and marrow offer the greatest po-tential fornewbonegrowth (Cushing, 1969;Sot- tosanti and Bierly, 1975; Amler, 1984). Thismaterial is obtained from either the anterior or theposterior iliac crest (Schallhorn, 1968;Dra- gooand Irwin, 1972). Schallhorn's reports of complete eradication of furcation and interprox- imalcraterdefects spurredinterestinthismaterial (Schallhorn, 1967 and 1968). Subsequently, ad- ditionalcase reports attested to the efficacy of337

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this approach when used by different clinicians to successfully treat furcations, dehiscences, and

defects of varying osseous morphology (Schal- lhorn et al, 1970; Haggerty and Maeda, 1971;Patur, 1974;Seibert, 1970;Mattout andRoche,

1984).Meanclinicalbonefillof3.33mmin182 defects and 4.36 mm in 7 defects has been re-

ported (Froum et al, 1975; Schallhorn et al.,1970). Patur (1974) indicated that grafting improved the results of treatment. In addition, amean bone apposition of 2.54 mm in crestal or zero-wall defects has been documented (Schal-

lhorn etal., 1970).

B.BoneAllografts

The need for an allogeneic source ofbone arosefrom theneedfor increaseddonormaterial and

theproblemsassociatedwithautogenousbone procurement, namely, the morbidity accomp- anying a

second surgical site and the need for a sufficient quantity of material to fill multiple defects

(Mellonig, 1980 and 1991). Three typesof bone allografts are used clinically. Underminer- alized

(mineralized), freeze-dried bone allograft (FDBA) and demineralized (decalcified), FDBA are used

routinely; frozen iliac cancellousbone and marrow areused sparingly.

1.IliacCancellousBoneandMarrowAllograft

Theneed forextensivecross-matchingofdo- nor and recipient and the possibility of diseasetransfer restrict the use of iliac cancellous bone andmarrow allograft (Hiatt andSchallhorn, 1971;Schallhorn, 1977).Ameancoronalgainofbone amounting to 3.07 mm in26patients at reentry hasbeen reported (Schallhorn andHiatt, 1972). When compared with open flap debridement of osseousdefects, allogeneic grafts of cancellous bone and marrow resulted in greater defect fill,1.6 mm (54% defect fill) for grafted sites and0.8 mm (33% defect fill) for nongraft sites (Scharad and Tussing, 1985). When comparedwith tricalciumphosphate, frozen allogeneicbone implants led to greater bone apposition and re-

duction inprobing depth (Strub etal, 1979).2.Freeze-DriedBoneAllograft

Undemineralized FDBA was introduced to periodontal therapy in 1976 (Mellonig et al.,1976). Freeze drying removes approximately95% of the water from bone by a process of subli-

mationinavacuum.Althoughfreezedryingkills allcells, themorphology, solubility, and chemical

integrity of the original specimen are main- tained relatively intact (Friedlaender, 1988;Mel- lonig,

1980 and 1991). Freeze drying also markedly reduces the antigenicity of aperiodon- tal bone

allograft (Turner and Mellonig, 1981; Quattlebaum etal, 1988).Atnotimecouldany donor-specificanti-HLA antibodies be detected in any human recipient who received several FDBA grafts

(Quattlebaum etal, 1988).FDBA is the only graft material that has undergoneextensivefield testing inthetreatment of

adultperiodontitis(Mellonigetal, 1976;Sepe et al, 1978; Sanders et al, 1983; Mellonig,1991). Field test studiesprovide information as toefficacy andfeasibilitybutsuffer from lackof

project control, erratic documentation, and equivocal investigator compliance. Eighty-nine

clinicians implanted a total of 997 sites with FDBA alone and 524 sites with FDBAplusau-

togenousbone(FDBA + A),(Mellonig, 1991). Sufficient data,asdeterminedbysurgicalreentry at 6

months, were collected to determinepre- dictability in 329 sites treated with FDBA and

176sites treated withFDBA + A. Completeor

>50%bonefill wasobtained in220(67%)sites treated with FDBA and 137 (78%) of the sites

treated with FDBA -I- A. Significant probing depth reduction occurred in 69 and 79% of the

sites, respectively (Mellonig, 1991). It canbe concludedfrom thisandotherstudiesthatFDBA in

combination with autogenousbone is more efficacious than FDBA alone, especially in the treatment

of furcation invasion defects (Pearson andFreeman, 1980;Sandersetal, 1983).Altiere etal (1979)

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investigated FDBA sterilized with threeMradsof7-irradiation, whencomparedwith

anongraftprocedurefordebridement intenpaired sites.Bothgraft andnongraft sitesdemonstrated>50%bone fill in60%of the sites.

Acomposite graft ofFDBA and tetracycline in a 4:1 volume ratio has shown promise in the

treatment of theosseous defects associated with338

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localizedjuvenileperiodontitis(YuknaandSepe,

1981;Evans etal, 1989).Astudy that compared FDBAwith andwithout tetracycline toa nongraftprocedure in 12 juvenile periodontitis patients demonstrated significantly greater bone fill and

resolution of osseous defects in grafted as op- posed tocontrol sites (Mabry etal, 1985).

3.Decalcified Freeze-DriedBoneAllograft

Urist and co-workers showed through nu- merousanimalexperimentsthatdemineralization of acortical bone graft induces new bone formation and greatly enhances its osteogenic potential

(Urist, 1965;Urist etal, 1967;Urist and Dowell, 1968;Urist etal, 1968and 1975).The workofUristhasbeenconfirmedbyothers(Ko- skinen et al, 1972;Chalmers et al., 1975;Oi- karien andKorhonen, 1979; Mellonig et al.,1981a andb). Demineralization with hydrochlo- ric acid exposes the bone inductive proteins lo-

cated in thebone matrix (Urist and Strates, 1970). Theseproteins are collectively calledbone mor-

phogenetic protein (BMP) (Urist and Strates,

1971). They are composed of agroup of acidic polypeptides that have been cloned and se-

quenced (Urist et al., 1983a and b;Wozney et al., 1988). In addition, there appears to beho-mology among bone inductiveproteins between mammalian species (Sampath and Reddi, 1987).

BMP stimulates the formation of new bone by osteoinduction (Urist et al, 1970). That is, thedemineralized graft induces host cells to differ- entiate intoosteoblasts (Harakas, 1984),whereas an

undemineralized allograft is felt to function by osteoconduction as it affords a scaffold for new

bone formation (Goldberg and Stevenson,

1987). The sequence of bone induction with a demineralized bone graft isbelieved to follow a

boneinductioncascade (Reddietal, 1987;Bow- ers and Reddi, 1991). At day 1, there is chem-otaxis of fibroblasts and cell attachment to the implanted demineralized bone matrix. Atday 5,

there is continued cell proliferation and differentiation of chrondroblasts. At day 7, chrondro-

cytes synthesize and secrete matrix. From days

10to 12, there isvascular invasion, differentiation of osteoblasts andbone formation, andmi-

neralization. By day 21 , there is bone marrow differentiation. This cascade for the induction of

endochondral bone has been shown to occur in heterotopic sites of animals grafted with demi-

neralizedbonematrix (Reddi etal., 1987). Ithas not been demonstrated to occur following im-plantation of this material in a periodontal osseous defect. Amore likely scenario for theper-

iodontal defect is the induction of new bone through the intermembranous route (Melloniget al,

1981b).

Libin et al (1975) were the first to report the use of cortical and cancellous decalcifiedFDBA (DFDBA) in humans. The three grafted sites responded with 4 to 10 mm of new bone

formation. CorticalDFDBAwasevaluated in27 intraosseous periodontal defects and yielded a mean

of 2.4 mm ofbone fill (Quintero et al,1982).Insixcases,Werbitt(1987)showedbone fillrangingfrom75to95%oftheoriginaldefect.

Theresultsofaradiographicanalysisofcan- cellous DFDBA in 16patients demonstrated a mean

bone fill of 1.38 mm, whereas sixcontrol sites showed 0.33 mm (Pearson et al, 1981). Thereasonfor thismeagerbone fill after agraft ofcancellousDFDBAmaylieinthefact thatthe bone inductive

proteins are located in the bone matrix(UristandIwata, 1973).Becausethemass ofbone matrix is

lower in cancellous bone than that incorticalbone, theyieldofnewbonecould be expected to be

lower with cancellous than cortical bone (Urist et al, 1970). Another controlled study in 47periodontal osseous defects demonstrated a meanbone fill of 2.6 mm (65% defect fill) in sites

treated with cortical DFDBA in comparison with 1.3 mm (38%defect fill) in sites treated without

DFDBA.

Rummelhart et al (1989) clinically compared DFDBA and FDBA in 11paired sites.Nostatistical difference inprobing depth reduction, clinical attachment gain, or bone fill was re-

ported, which might havebeen reflective of in- sufficient inductiveboneprotein in DFDBA or the

types and depths of thegrafted lesions. Ad- ditional factors might also have influenced the decisionto use a mineralized or demineralized preparation. Theprocessing ofbothpreparations included

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multiple immersions in absolute ethanol. The DFDBA underwent further processing that included

immersion in 0.6N HC1 (Mellonig,

339

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1991). Each of these chemical processes was thought to inactivate HIV (Martin et al, 1985;Resnick etal, 1986;Quinnan etal, 1986).

4.Allografts ComparedwithAlloplasts

Both FDBA and DFDBA havebeen com- paredtoporousparticulatehydroxyapatite, asyn- thetic

or alloplastic bone graft material. Studies byBurnettetal. (1989)andBowenetal (1989) suggestthat there is little difference inposttreat- ment clinical parameters between allograft and the

hydroxyapatite graft sites. Another study suggests a slight difference in favor of the alloplast(Oreamuno et al, 1990). Histologically, grafts of DFDBA heal with regeneration of theperio-dontium (Bowers etal., 1989c), whereas grafts of syntheticbonehealbyrepair (Baldocket al.,1985; Froum et al, 1982; Stahl et al, 1986; Kenney et al, 1986; Carranza et al, 1987).Therefore, thechoiceofmaterial willdepend in part on theobjectives of the clinician.

V.WOUNDHEALINGWITH PERIODONTAL BONEGRAFTS

The objectives of the clinician who usesbone grafts are (1)probing depth reduction; (2) clinical

attachment gain; (3)bone fill of the osseous defect; and (4) regeneration of new bone, cemen-

tum, andperiodontal ligament (Schallhorn, 1977). Case reports and controlled clinical trialsprovidevaluable information with respect to the first three objectives. They do not reveal the type of wound

healing adjacent to thepostgrafting root surface. Therefore, histologic analysis of thenatureof theattachmentapparatus isneeded todetermine true regeneration of theperiodontium.

A.Animal Studies

Histologic evaluations in animals are of in- terestbecause they indicate thepotentialofagraftmaterial toproduce favorable results. Ina review of the studies performed over the past severaldecadescomparinggraftandnongraftprocedures inartificially created defects inanimals,75%of

the studies indicated that more favorable results mightbe obtained following theplacement of abonegraft(Table2).Noneofthenongraftcontrol sites were found tobe superior tografted sites. Theresults of animal experimentation mustbe viewed with caution, and the tendency to ex- trapolate

this information directly to the human situation shouldbeduly tempered.

B.Human Studies

Only in clinical trials can the true potential of any graft material to regenerate theperiodon-tium be analyzed. To date, approximately 159 human periodontal bone grafts have been re-moved enbloc andprocessed for histologic evaluation (Dragoo and Sullivan, 1973; Ross and

Cohen, 1968; Nabers et al, 1972; (Hiatt and Schallhorn, 1973; Hawley and Miller, 1973;Froumetal., 1975;Moomaw, 1978;Hiattet al,1978;Listgarten and Rosenberg, 1979;Moskow et al, 1979; Langer et al, 1981;Evans, 1981;Froum et al, 1983;Dragoo and Kaldahl, 1983; Bowers et al, 1982;Bowers, 1989a, b, and c).Most human histologic evaluations have been criticizedbecause they failed to adequately dem-onstrate that the adjacent root surface wasbio- logicallycontaminated anddevoidof itsconnec- tivetissueattachment.Forexample,biopsieswere commonly evaluated from the most apical level of rootplaning (Hawley and Miller, 1975;Hiatt etal, 1978;Moskow etal, 1978),from anotch placed incementum withaburatthebaseofthe defect (Nabers et al, 1972; Moomaw, 1978; Listgarten andRosenberg, 1979), from anotch placed in cementum at the level of the alveolar crest (Dragoo andSullivan, 1973), or from a naturally occurring notch in the root surface (Ross and Cohen, 1968;

Evans, 1981). All of these histologic reference points, although highly suggestive of a rootexposed to theoralbacterial contamination, didnotprove thattheroot surface had lost its connective

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tissue attachment (periodontal ligament). Therefore, reattachment rather than regeneration mighthavebeentheresult.Us- ing the above cited examples for a histologic reference point, new bonecementum and periodontal ligament havebeen observed following grafts of corticalbone chips(Nabersetal, 1972),

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TABLE2

AnimalControlled HistologicStudieswithBoneAutograftsand

Allografts intheTreatmentofPeriodontalOsseous Defects

Graft

material

OC

oc

ICBM

ICBM

ICBM ECBM

ICBM ECBM

ICBM

ICBM ICBM

ICBM ICBM

Defecttype

Animal created

4M Intraosseous

4M 2-and3-Wall

10D Intraosseous

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10D Furcation

6M Furcation

12M 3-Wall

19M Furcation

6D Furcation

8M Intraosseous

10D Furcation

6D Furcation

Results

Asoonerandgreater osteogenic activity withsmallparticle bonegraft than controls

Inearlystages,grafted defects demonstrated amoreadvanced

levelof regeneration thancontrolsGrafteddefectsmaybe eliminatedby induc- tionofbone;control defectshealbyadap- tationofepithelial

attachment

Acoronal increaseof2 to3mmofbonewith graft

Nonewbonewith control

ICBMandfrozen ECBMyieldeda higherfrequencyof regenerationthan freshECBMand controls Regeneration

isob-

tainedwithequalsuc-

cesswithandwithout graft

Newbone indeepest portionofdefectwith graft

Nonewbonewithout graft

Osseousgraftsdidnot improve results

Bothgraftandcontrol healedwithanepithe- lialliningalongthe

rootsurfacewithno newconnective tissue Flapsupportbythe bonegraftmayfacili- tate regeneration Abundantnewbone, newcementum,and noankylosiswith

graft;controldefects

filledwithconnective tissueandnew cementum

Ref.

Rivaultetal. (1971)

Coverlyetal. (1975)

Yuktanandana

(1959)

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Pattersonetal. (1967)

Ellegaardetal. (1973)

Elegaardetal. (1974)

Ellegaardetal. (1975)

Nilveusetal. (1978) Catonetal. (1980)

Klingeetal. (1985)

Passaneziet al. (1989)

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TABLE2 (continued)AnimalControlled HistologicStudieswithBoneAutograftsand

Allografts intheTreatment of PeriodontalOsseous Defects

Graft

material

CBMA

CBMA FDBA

FDBA DFDBA

DBP

DFDBA

DFDD

ICBM DFDBA

Animal

12D

4M

4D

4M

27D

8D

4D

6D

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3DDefect type

created

Intraosseous

2-Wall

2-Wall

Intraosseous

Intraosseous

Intraosseous

Furcation

2-Wall

3-Wall

Furcation

Results

Nosignificant difference inhealingbe- tweengraftand controlAllograft induceda

morerapidosseous repairthancontrols Convincingevidenceof acceptabilityofgraft; noadvantageordis-

advantage inusing graft

Significantly morere-

generationwithgraft thancontrolGraftwas replacedby

newboneandmar- row;lessnewboneat controlsites

DBPsuccessfullyin-

ducednewbone;no differenceswereseen betweentestand control

Grafthealedbyregen- eration;controlhealed bya longjunctional epitheliumComplete regeneration

of lostattachmentap- paratuswithgraft;

longjunctionalepithe- liumtobaseofdefect withcontrols

Graftsshowedmore pronounced regenera- tionandhigherperio- dontalattachment

thandidcontrols

Ref.

Hiatt(1970)

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Poulsometal. (1976)

Hurt (1969)

Mellonig

(1981)

Narangand

Wells (1972)

Sonisetal. (1985)

Blumenthalet al. (1986)

Waaletal. (1988)

Wadaetal. (1989)

OC = Osseouscoagulum autograft.

ICBM = Intraoralcancellousboneandmarrowautograft.

ECBM = Extraoral (iliac)cancellous boneandmarrow autograft.

CBMA = Cancellous boneandmarrow allograft.

FDBA = Freeze-driedboneallograft.

DFDBA = Decalcified freeze-dried bone allograft.

DFDDA = Decalcifiedfreeze-drieddentinallograft.

DBP = Demineralizedbonepowder.

D = Dog.M = Monkey.

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osseous coagulum (Evans, 1981),bone blend (Froum et al, 1975), intraoral cancellousbone andmarrow (Ross and Cohen, 1968; Hiatt and Schallhorn, 1973;Hawley andMiller, 1975;Hiatt et al.,1978; Listgarten and Rosenberg, 1979; Langer et al., 1981), iliac cancellous bone and marrowautograft (Dragoo and Sullivan, 1973; Hiatt et al., 1978), iliac cancellous bone and marrowallograft (Hiatt et al., 1979; Listgarten and Rosenberg, 1981), and undemineralized FDBA(Moomaw, 1978).

Currently, only a notch placed in the most apical level of calculus on the root surface is

considered scientifically validproof of regeneration of an attachment apparatus (Cole et al.,1980;Froum etal, 1983;Dragoo and Kaldahl,1983;Bowers etal., 1989a,b, and c). Using this criterion, newbone, cementum, andperiodontalligamenthavebeen identified followinggraftsof osseous coagulum-bone blend (Froum et al.,1983)andDFDBA(Bowersetal, 1989a,b,and c).

C.Bone Induction

It hasbeen stated that there is "little indi- cation that (periodontalbone) grafts of cortical or

cancellousbone haveany inductive effect on the formation of newbone. Also, there is little reason

tobelieve that suchbone grafts would stimulateconnectivetissueattachmenttotheroot surface"

(Egelberg, 1987). This concept was evaluated in a studyby Bowers etal. (1989b). They comparedthe healing of intraosseous defects withandwithout theplacementofDFDBA in defects about teeth

that received coronalec- tomyandwerecompletelycoveredbysofttissue. The most apical level of

calculus on the root servedasahistologic referencepointtomeasure periodontal regeneration in 30

grafted and 19 nongrafted defects. Results indicated that in the submerged environment, regeneration

waspos- sible with and without theplacement of abone graft. However, morenewattachment

apparatus formed in grafted than nongrafted sites. In addition,newbone,newcementum,and

periodontal ligament occurred more frequently in grafted thannongrafted sites.Theseresultsstrongly

sug-

gest thatbonegrafts dohavean inductive effect on theperiodontium.

D.Healing Sequence

The healing sequence of an autogenous periodontal bone graft has been identified as initi-

ation of newbone formation at 7 d, cemento- genesisat21d, andanewperiodontal ligament at 3

months (Dragoo, 1972). By 8 months, the graft shouldbe incorporated into hostbone with

functionally orientedfiberscoursingbetweenbone and cementum. Maturation may take as longas

2 years (Dragoo, 1972; Dragoo and Sullivan,

1973).

E.RootResorptionandAnkylosis

Becausegranulation tissuederived frombone may induce root resorption andankylosis, theuse of

bone grafts hasbeen questioned (Karring et al., 1980). Root resorption is reported as a se- quela

of osseous grafting in humansbut appears to be a significant disadvantage only with fresh iliac

cancellousbone and marrow (Schallhorn et al., 1970; Schallhorn, 1972; Dragoo and Sulli- van,

1973;Hoffman and Flanagan, 1974;Hiatt etal., 1978).Clinicalevidenceofrootresorption wasnotedin 7of 250 sites (3%inone reported series (DragooandSullivan, 1973)and 16of275 sites (5%) in

another (Hiattetal., 1978).Freez- ingseemstoattenuate thisproblem (Schallhorn,1972). Recently, Bowers and co-workers re- portedonaseriesof62casesgraftedwithDFDBA and

removed enbloc at6months for histologic observations (Bowers etal., 1989b and c). Ex- tensiveroot resorption was not observed. Be- cause this phenomenon has been observed only withfresh

material,viablemarrowcellsmayplay an etiologic role (Ellegaard, 1976). The most probable causeof root resorption is poor post- surgical plaque control with subsequent chronic gingival

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inflammation (Dragoo and Sullivan,

1973). This hypothesis hasbeen strengthenedby histologic findings that connective tissue in re-

sorptivedefects alwayscontainedaninfiltrateof inflammatory cells (Ellegaard, 1976). Root re-

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sorption andankylosis followingbonegrafts are moreprevalent in animal models (Ellegaard et al.,

1973 and 1976; Karring et al, 1980 and1984;Nyman et al, 1980) than they are in humans and maybe a function of the healingpo-tential animalmodel (Sonisetal, 1985;Aukhil etal, 1990).

Apical migration ofjunction epithelium between the alveolarbone and the root surface hasbeen offered as anexplanation of why resorption only infrequently takes place after regeneration

attemptswithbonegrafts (ListgartenandRosen- berg, 1979;Karringetal, 1980;CatonandZan- der,1976;Moskow etal, 1979).Thejunctional epithelium was specifically located in74human biopsieswhere bone grafting was performed (Bowersetal, 1982).Thejunctional epithelium was locatedapical to the alveolar crest in 14 (19%)sites.Inanadditional32graft sites,Bow- ersetal (1989c)showed that grafted sites con- sistentlyformedanewattachmentapparatus.The junctional epithelium

proliferated apically, but the epithelium was rarely observed apical to the level of active bone

formation. Junctional epithelium was never observed beyond the levelof newcementumformation(Bowersetal, 1989c). Authors reporting epithelial migration between the grafted site and the rootsurface also report chronic inflammatory cells adjacent to the epithelium (Hiatt etal, 1978)orextending into the marrow spaces (Moskow et al, 1979). Poor plaque control is therefore alikely explanation asproliferation of epithelium is more extensive and rapid in surgical sites with

no postoperative plaque control than in areas where bacterial de- posits have been removed(Yumet and Poison,1985).

VI.TISSUE BANKINGANDFDBA

Thepossibility ofdisease transfer withbone allografts is unlikely if the material isprocured andprocessedbyusingestablished tissuebanking protocols (Friedlaender, 1987; American Asso- ciationof Tissue Banks, 1984). If exclusionary techniques such asmedical and social screening, antibodytesting, direct antigen tests, other ser- ologic tests,bacterial culturing, autopsy, and follow-upstudiesofgrafts from thesamedonorare

used, the possibility of disease transfer are approximately one in2million (Bucketal, 1989).Freezing thebone allograft reduces the risk to onein8million(Bucketal, 1990).Anestimated40,000periodontal grafts of mineralized andde- mineralized bone are performed annually (Mel-lonig, 1991).There areno reported casesofdis- ease transfer with processed (treatment withvirucidal agents and demineralization in hydro- chloric acid) FDBA.

Concernswithdisease transfer have led some tissue banks to sterilize the bone allograft with

irradiation or ethylene oxide. Irradiation of abone allograft is reported both to markedly attenuate(Buring, 1967;Towle et al, 1987;Munting et al., 1988) and not to affect (Wientroub et al,1988)boneinduction.Furthermore,thecurrently useddoseof 1.5Mradwillnotreliably inactivate HIV

inboneallografts withanacceptable safety margin (Conway et al, 1990). There is little questionthatethyleneoxide sterilization renders

abone allograft noninfectious (Eastlund et al,1989).However, likeirradiation,ethyleneoxide may interfere withbone induction (Zislis et al,1989). Residual levels of ethylene oxide in the graft have been shown tobe toxic to fibroblastsand cause morphologic changes that may ormay not be reversible (Kudryk, 1990). Others have

found ethylene oxide sterilization tobe accept- ableand safe (Proloetal, 1980).Theprocessing of abone allograft for dental usewill usually include the following steps (Mel-

lonig, 1991):

1. Corticalbone is harvested in a sterile man- nerwithin 12hof death of thedonor. Cor- ticalbone is less antigenic than cancellous bone (Friedlaender et al, 1976) and has a higherconcentrationofbone-inductiveproteins (UristandDowell, 1968;Uristet al,1970).

2. The bone is rough cut to 0.5 to 5 cm and immersed in 100% ethanol for 1h. Viral

infectivity is undetectable within 1min of treatment (Resnick et al, 1986), and the ethanolcompletelypenetrates through the corticalbone (Prewitt etal, 1991).

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3. Thebone isfrozen. Freezingdecreases the riskofdiseasetransfer (Bucketal, 1990).4. The corticalbone isground toafinalpar-

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tide sizeofapproximately 250to800

Particle sizes within this range havebeen shown topromote osteogenesis, whereasa particle

sizebelow 125 |xminducesamac- rophage response (Mellonig and Levey,

1984).

5. The graft isagain immersed inethanol.

6. Thebonemayormaynotbedimineralized.

7. The allograft is freeze dried. Freeze drying permits long-term storage and reduces an-

tigenicity (Turner and Mellonig, 1981; Quattlebaum etal, 1988).

VII.GUIDEDTISSUE REGENERATION AND BONE GRAFTS

Case reports and controlled clinical trials have indicated that theplacement of aphysicalbarrier

between the gingival flap and the root surface enhancesthepotentialforwoundhealing(Nyman et

al, 1982;Beckeretal, 1987and 1988;Pon- toriero et al, 1988 and 1989; Lekovic et al,1989;Caffesse etal, 1990;Gagerand Schultz,1991). Thisprocedure retards apical migration of epithelium, excludes gingival connective tissue

cells from the wound, and favors healing from the periodontal ligament cells (Gottlow et al.,

1986). The histologic result is new attachment (Gottlow etal, 1986;Beckeretal, 1987; Nymanetal, 1987).

Arecent study indicates that theperiodontal ligamentcellsmigrateonlyashortdistanceand, atthesamerate,withandwithouttheplacement ofaphysicalbarrier (AukhilandIglhaut, 1988). Therefore,

the critical role of aphysicalbarrier maybe thatof spacecreation toallow migrating cells sufficienttime to undergo amplifying cell divisionandpopulate therootsurface (Aukhilet al., 1990). In

addition, cellsfrom thebonemay play a role in guided tissue regeneration. Cells from the endostealspaces of alveolarbone can synthesizecementumlike tissueandmaymigrate fromboneintothe

periodontalligament(Melcheretal, 1986).

A number of case reports suggest that the combination of anosseous graft and thephysicalbarrier enhances bone fill and promotes more favorable results (Schallhorn and McClain, 1988).Anderegg et al (1991) compared 15pairs of

furcation defects in15patientstreatedbyDFDBA plusanexpandedpolytetrafluoroethylene (Gore- Tex

Periodontal Material, W. L. Gore &Asso- ciates, Flagstaff, AZ)physicalbarrier orby a physical

barrieralone.Theyfoundbothhorizon- tal and verticalbone fill tobe more favorable with theuse

of thegraft plusbarrier. However, Garrett et al. (1988), using a graft of DFDBA andduramatersheetsbetween the replaced surgical flaps and the tooth surfaces, found limited improvementofthe

treated defects overpretreat- ment levels. Stahl and Froum (1991) have most recently shown

cementogenesis on teeth treated by osseous allograft and an expanded polytetra- fluoroethylene

membrane. Osseous remodeling and crestal osteogenesis were seen in association with

cementogenesis. New attachment was histologically present within two of four calculus notches

in this sample.

VIII.FUTURE DIRECTIONS

Althoughbone grafts havebeen shown tobe efficacious for the treatment of periodontal os-seous lesions, the reconstruction appears tobe limited toameanbonefill ofapproximately 3.0 mm

irrespectiveofthetypeofbonegraft material (Table 1). Because the ultimate goal of periodontal

therapy is to reverse the disease process and completely regenerate theperiodontium, additional

stimuli toenhance theregenerativepro- cessclearlyareneeded. Polypeptidegrowth factors, apotent

class of natural biologic response modifiers, may be the answer. Factors such as osteogenin

(BowersandReddi,1991)orthecom- bination ofplatelet-derived growth factor (PDGF) andinsulinlike

growthfactor(IGF)(Lynchet al,1989) may havepotential. Other growth factors such as transforming growth factor- (3 and basic

fibroblast growth factor may also have aplace (Graves and Cochran, 1990). However, the use of

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growth factors (GFs) toaugmentperiodontal regeneration alsoposesmanyquestions, suchas

1. What is theproper doseof GFs?2. WhatisthebestbiologiccarrierfortheGF?3. When should the GFbe released into the healing cascade?

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4. What are thepossible local and systemic sideeffects of GFs?

5. Cantheeffects oftheGFsbelimited tothe local environment?

6. Can results obtained with GFs in animal model systemsbeextrapolated tohumans?

7. What isthemechanismofactionofGFsin theperiodontal environment?

8. What is the most effective GF in theperiodontal environment?

IX. CONCLUSIONS

1. Numerouscasereportsandcontrolledclin- ical studies indicate that autogenousbone grafts canbe used successfully inperiodontal therapy.

2. Multiple histologic reports suggest that regeneration of a new attachment apparatus ispossible withdifferent typesof autogenousbone grafts.

3. Root resorption and ankylosis may be observed only following grafts of fresh iliaccancellousbone and marrow.

4. Iliaccancellousboneandmarrowareagraft of high osteogenicpotential.

5. BothFDBA andDFDBAhavebeen shown tobe clinically effective in the reconstruction ofperiodontalbone defects.

6. Sites implanted with DFDBA demonstrate moreprobing depth reduction, clinical at- tachmentgain, andbone fill than similar defects that arenot grafted.

7. Regeneration of newbone, cementum, and periodontal ligament is a frequent finding withgrafts of DFDBA.

8. Boneformation maybeenhanced ifguided tissueregeneration attemptsareaugmented withbonegrafts.

9. Bone allografts and alloplasts offer similar advantages with respect tobone fill. Re- generationisgenerally theresultafter grafts ofDFDBA,whereasrepairistheresult after grafts of syntheticbone.

10. Dental bone allografts are safe for human use if proper exclusionary techniques andprocessing are employed.

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