REVIEW

Alveolar ridge preservation. A systematic review

Attila Horvth & Nikos Mardas & Luis Andr Mezzomo &Ian G. Needleman & Nikos Donos

Received: 31 December 2011 /Accepted: 14 May 2012 /Published online: 20 July 2012# Springer-Verlag 2012

AbstractObjective The objective of this paper is to examine theeffect of alveolar ridge preservation (ARP) compared tounassisted socket healing.Methods Systematic review with electronic and hand searchwas performed. Randomised controlled trials (RCT), controlledclinical trials (CCT) and prospective cohort studies wereeligible.Results Eight RCTs and six CCTs were identified. Clinicalheterogeneity did not allow for meta-analysis. Average changein clinical alveolar ridge (AR) width varied between 1.0and 3.52.7 mm in ARP groups and between 2.5and 4.60.3 mm in the controls, resulting in statisticallysignificantly smaller reduction in the ARP groups in five outof seven studies. Mean change in clinical AR height variedbetween +1.32.0 and 0.71.4 mm in the ARP groups andbetween 0.81.6 and 3.61.5 mm in the controls. Heightreduction in the ARP groups was statistically significantly less

in six out of eight studies. Histological analysis indicatedvarious degrees of new bone formation in both groups. Somegraft interfered with the healing. Two out of eight studiesreported statistically significantly more trabecular bone for-mation in the ARP group. No superiority of one technique forARP could be identified; however, in certain cases guidedbone regeneration was most effective. Statistically, signifi-cantly less augmentation at implant placement was neededin the ARP group in three out of four studies. The strength ofevidence was moderate to low.Conclusions Post-extraction resorption of the AR might belimited, but cannot be eliminated by ARP, which at histolog-ical level does not always promote new bone formation. RCTswith unassisted socket healing and implant placement in theARP studies are needed to support clinical decision making.Clinical relevance This systematic review reports not only onthe clinical and radiographic outcomes, but also evaluates thehistological appearance of the socket, along with site specificfactors, patient-reported outcomes, feasibility of implantplacement and strength of evidence, which will facilitate thedecision making process in the clinical practice.

Keywords Tooth extraction . Bone resorption . Implant sitedevelopment . Bone substitute . Bone regeneration .

Human histology

Introduction

Periodontal disease, periapical pathology and mechanical trau-ma often result in bone loss prior to tooth removal [1]. Further-more, traumatic extraction has also been associated withadditional loss of bone. In the healing phase after extraction,alveolar bone undergoes additional atrophy as a result of thenatural remodelling process [27]. This begins immediately

A. Horvth :N. Mardas : L. A. Mezzomo : I. G. Needleman :N. Donos (*)Unit of Periodontology, Department of Clinical Research,UCL Eastman Dental Institute,256 Grays Inn Road,London WC1X 8LD, UKe-mail: n.donos@ucl.ac.uk

A. HorvthDepartment of Periodontology, Semmelweis University,Budapest, Hungary

L. A. MezzomoPontifical Catholic University of Rio Grande do Sul,Porto Alegre, Brazil

I. G. NeedlemanInternational Centre for Evidence-Based Oral Health,UCL Eastman Dental Institute,London, UK

Clin Oral Invest (2013) 17:341363DOI 10.1007/s00784-012-0758-5

after extraction and may result in up to 50 % resorption of thealveolar ridge (AR) width even in 3 months [1]. Post-extractionAR resorption may have an impact on dental implant place-ment, since sufficient vertical and horizontal volume of alveolarbone should ideally be present at the site of insertion [8].

Alveolar ridge preservation (ARP) procedures have beenintroduced to maintain an acceptable ridge contour in areasof aesthetic concern, as well as to prevent alveolar ridgeatrophy and maintain adequate dimensions of bone in orderto facilitate implant placement in prosthetically driven posi-tions [9, 10]. Several methods have already been investigat-ed for ARP in preclinical models [1114] and clinicalstudies, such as socket grafting with autogenous bone[15], demineralised freeze-dried bone allograft (DFDBA)[1517], xenografts, like deproteinized bovine-bonemineral (DBBM) [18], alloplasts [19] and bone morpho-genic proteins (BMP) [20]. Guided bone regeneration(GBR) with or without bone grafts has also been evaluated[9, 10, 2125].

Although some of the above bone substitutes wereable to limit the resorption of post-extraction alveolarridge up to a certain extent, the quality of the newtissue in the socket varied broadly. The remnants ofthe grafts often interfered with the normal healing pro-cess in line with preclinical results [1517, 26]. Anumber of review articles on ARP have been publishedin the last decade [2732]. However, a systematic as-sessment of the nature and quality of the newly formedtissue alongside methodological quality and risk of biasof the studies has not been carried out. Furthermore,non-controlled prospective and retrospective studies aswell as case series were also included in most of theprevious reviews without the comparison to the controlgroup of unassisted socket healing [3336].

Therefore, the objective of the present systematic reviewwas to investigate the effect of ridge preservation on theresidual alveolar ridge dimensions and on histological char-acteristics, compared to unassisted socket healing.

Methods

Prior to commencement of the study, a detailed protocol wasdeveloped and agreed upon by the authors based on theCochrane Collaboration guidelines and previous reviewspublished by our group [3741].

Focused question

Following tooth/root extraction in humans, what is the effectof ridge preservation on the residual alveolar ridge dimensionand on histological characteristics, compared to unassistedsocket healing?

Definition

Whilst socket preservation has widely been employed todepict a certain procedure, we believe that the objective ofthese interventions is to preserve the dimension of the AR.Therefore, we have used the term Alveolar Ridge Preser-vation to define such procedures.

Types of studies

Longitudinal prospective studies were included, i.e. RCTs,CCTs and cohort studies with control group.

Populations of studies

Healthy individuals, without any age limit, who underwentany type of ridge preservation following permanent toothextraction, were included. Smokers and patients with historyof periodontal disease were not excluded. The minimumnumber of subjects per group was five. However, no limitwas set for study follow-up period.

Types of interventions

Test groups

Studies reporting on any of the following types of interven-tions were included: socket grafting (autograft, allograft,xenograft, alloplastic materials); socket sealing (soft tissuegrafts); GBR (resorbable/non-resorbable barriers); biologicalactive materials (growth factors) and combinations of theabove techniques/materials.

Control groups

The control groups of the included studies comprised emptysockets, i.e. unassisted socket healing.

Outcome variables

The primary outcomewas the change in oro-facial (horizontal)and apico-coronal (vertical) AR dimensions. Secondary out-comeswere the following: (1) change in buccal plate thickness;(2) bone volume alteration following extraction; (3) complica-tions; (4) histological healing characteristics; (5) site eligibilityfor placement of an adequate size dental implant with orwithout further augmentation; (6) patient-reported outcomes,such as quality of life and (7) health economics.

Risk of bias and methodological quality assessment

In order to evaluate the methodological quality and risk ofbias of individual studies, we used a combination of

342 Clin Oral Invest (2013) 17:341363

parameters from the Cochrane Collaboration and Consoli-dated Standards of Reporting Trials (CONSORT) statement.The following parameters were assessed and taken intoconsideration in the final analysis: sample size calculation,statement of eligibility criteria, ethics approval, informedconsent, baseline homogeneity, randomisation method, allo-cation concealment, masking, calibration, follow up, protocolviolation, method of statistics, unit of analysis, CONSORTimplementation, International Standard Randomised Con-trolled Trial Number Register (ISRCTN) and funding disclo-sure. Methodology unique to RCTs was not assessed in CCTs,i.e. randomisation and concealment of allocation.

Randomisation was accepted as adequate, in case theallocation sequence was correctly generated either bycomputer, toss of a coin, throwing dice, etc. Quasirandomisation, e.g. birth dates, hospital numbers werenot accepted. Adequacy of allocation concealment wasaccepted if the sequence was concealed, until interven-tion was assigned (e.g. in sequentially numbered andsealed opaque envelopes, remote computer or centraltelephone). Statistical analysis was judged as adequateif appropriate statistical method was selected to accom-modate to the characteristic of the each individual data(e.g. number of groups and investigated categories, sizeof samples, normally distributed or skewed data, para-metric or non-parametric, paired or unpaired, numericalor categorical variables). Statistical significance was ac-cepted in case of confidence interval (CI) >95 % (p99.9 % (p

interface. A three-stage selection of the resulted hits wasperformed independently and in duplicate by two reviewers(AH and LAM). In order to reduce errors and bias, a cali-bration exercise was performed with the first 500 titles,resulting in 96.4 % agreement. In case of disagreement atthe title selection stage, the trial was included in the abstractstage. At the abstract and full text selection any disagree-ments between the above reviewers were resolved by dis-cussion. If unresolved, a third reviewer (NM) was involvedfor arbitration. The reasons for exclusion were recordedeither in the Reference Manager (abstract stage) or in aspecific data extraction form (full text stage). The level ofagreement was determined by Kappa score calculation.

Research synthesis

Studies were grouped by research design and their chiefcharacteristics. Outcomes were recorded in evidence tables.In view of the marked heterogeneity, no meta-analysis wasconducted. Instead, a narrative synthesis was undertaken.

Results

Search sequence

The electronic search yielded 6,216 relevant hits after re-moval of duplicates (Fig. 1). Subsequently, 157 titles wereselected for the abstract stage. Following investigation ofthe abstracts, 42 articles qualified for full text evaluation.Four extra papers were then added as a result of the handsearch. Assessment of these articles resulted in the following

14 publications eligible for the review [17, 1921, 2325,4248]. The excluded full text papers along with the reasonsfor exclusion are listed in Table 1. The most typical reasonsfor exclusion were lack of control group with unassistedsocket healing; use of retrospective design; assessment ofdimensional changes of the AR only on periapical two-dimensional radiographs, or on casts taken from soft tissuelevel; and surgical removal of third molars.

The Kappa score for agreement between the reviewers (AH,LAM) at the abstract and full text selection level, was 0.96 and0.90, respectively, indicating a high level of agreement.

Study characteristics

In the 14 included articles (eight RCTs and six CCTs) theefficacy of ARP techniques was evaluated clinically bymeans of direct measurements of the residual alveolar ridgedimensions during re-entry procedures, radiographically bymeans of computer tomography or histologically from tre-phine biopsies taken at re-entry during osteotomies forimplant placement (Tables 3 and 4). No cohort studies wereindentified. Limited data were reported on confoundingfactors, such as periodontitis, smoking, systemic diseaseand medication. The extraction site distribution was fairlyheterogeneous. In some studies ARP was performed only inmaxillary anterior sockets [42, 46, 47], whereas such restric-tion was not employed in other studies. The residual bonevolume around the investigated sockets, e.g. the presence/absence and width of the buccal bone plate varied fromseverely compromised [20, 46], to completely intact, buccalbone (Table 3) [17, 21, 42].

Intervention characteristics

With regard to the techniques or materials used for ARP, theincluded studies were grouped into three categories (Table 3);

1. Bone grafts/substitutes2. GBR3. Biological active materials.

In the majority of the included studies, various bonegrafts were utilised, such as autologous bone marrow [47],plasma rich in growth factor (PRGF) with or without autol-ogous bone [43], DFDBA [17], DBBM [46], calcium sul-phate hemihydrates [42, 45] and bioactive glass [17].Alloplastic polyglycolide/polylactide (PGPL) sponge wasalso employed [19, 48]. GBR technique was applied usingnon-resorbable expanded polytetrafluoroethylene (e-PTFE)[24] or resorbable (PGPL) [25] barrier. Resorbable collagenmembrane was also employed in combination with FDBA[23] or corticocancellous porcine bone [21]. Biological ac-tive material, namely bone morphogenic protein (rhBMP-2)was used on a collagen sponge carrier in one study [20].

Electronic search6.216 titles

Included publications14

Relevantabstracts

Full-text analysis 45

Relevant full-texts42

6,059 Excluded based

on the title

115Excluded based on the abstract

32Excluded based on the full-text

3 Included as a result of hand search

Kappa score 0.96

Kappa score 0.90

1 Included as a result of final search

Fig. 1 Flow chart of the screening process

344 Clin Oral Invest (2013) 17:341363

Table 1 List of excluded full text papers and reasons for exclusion

First author(year of publication)

Journal Reasons for exclusion

Bianchi (2004) Int J Periodont Rest Dent Retrospective analysis

Single-arm of the included Fiorellini et al. (2005)

Bolouri (2001) Comp Cont Educ Dent Reported on optical density on two-dimensional radiographs

Brawn (2007) Impl Dent Case report

Brkovic (2008) J Can Dent Assoc Case report

Carmagnola (2003) Clin Oral Impl Res Lack of real control group, resembles to a retrospective analysis(extreme difference in follow-up period between tests and controls.T1: 4 months; T2: 7 months; C: 1-15 years, mean: 7.8 years)

Cranin (1988) J Biomed Mat Res Case series without control group

De Coster (2009) Clin Impl Dent Relat Res Case series

Retrospective study as stated by the authors in the discussion

Healing period varied between 1.5 months and 1.5 years

Neither histomorphometry nor clinical or radiographic measurementsreported in the results

Graziani (2008) J Cranofac Surg Extraction of fully impacted third molars

Linear measurements on OPG

Gulaldi (1998) Oral Surg Oral MedOral Pat Oral Rad End

Extraction of fully impacted third molars

Linear measurements on OPG and scintigraphy

Primary outcome was to analyze bone metabolism

Heberer (2008) Clin Oral Impl Res Case series without control group

Hoad-Reddick (1994) Eur J Prosth Rest Dent Two-dimensional linear measurements obtained from OPG and cephalometry

Lack of defined landmarks

Surgical procedure was not described

Hoad-Reddick (1999) Eur J Prosth Rest Dent Description of a method for measurements on casts

Neither socket preservation procedure nor the results were described.Soft tissue punch technique only

Howell (1997) Int J Periodont Rest Dent Case series without control group

Jung (2004) Int J Periodont Rest Dent Case series without control group

Primary outcome was soft tissue healing

Kangvonkit (1986) Int J Oral Maxillofac Surg Based on OPG and lateral cephalogram only

Evaluation method remains unclear

Primary outcome was the biocompatibility of HA cones

Karapataki (2000) J Clin Periodontol Extraction of fully impacted third molars

Primary outcome was to assess the periodontal status ofsecond molars after extraction of third molars

Kerr (2008) J Periodontol No biomaterials were used to preserve the ridge dimensions,therefore did not address the focused question

Kwon (1986) J Oral Maxillofac Surg Based on OPG and lateral cephalogram only

Evaluation method remains unclear

Lack of description of the measurement methods

Molly (2008) J Periodontol Control group was covered by an e-PTFE membrane,thus lack of unassisted control sockets

Munhoz (2006) Dento Maxillofac Radiol Extraction of fully impacted third molars

Two-dimensional evaluation of periapical radiographs

Norton (2002) Int J Oral Maxillofac Impl Case series without control group

Resembles to a retrospective design(healing period ranged from 3 to 11 months)

Page (1987) J Oral Maxillofac Surg Case report

Pape (1988) Deutsche ZahnarztlicheZeitschrift

Augmentation of a resorbed ridge

Clin Oral Invest (2013) 17:341363 345

None of the included studies used the socket sealing tech-nique. Primary flap closure was achieved in 9 out of 14studies, while the sockets left uncovered in the rests. Varioustypes and amounts of antibiotics and antiseptic rinses wereadministered for different duration in studies reporting onpostoperative care. Finally, average healing period rangedfrom one to nine months.

Outcome characteristics

Clinical outcomes

Eight out of the 14 included studies investigated the efficacyof various ARP techniques to preserve the pre-extractionridge dimensions using intra-surgical hard tissue measure-ments taken during re-entry procedure [19, 21, 2325, 42,44, 47]. In these studies, ARP was performed in 137 socketsof 119 patients and compared to 120 sockets that left to healwithout any treatment in a total of 92 patients (Table 3).

Bone graft Four studies evaluated changes in AR dimen-sions following grafting of the socket. Two studies were RCTs[42, 47] and two were CCTs [19, 44]. Healing time variedfrom 3 to 6 months [19, 42, 44, 47].

The horizontal (bucco-lingual) changes of the alveo-lar ridge were assessed in three studies [42, 44, 47].The AR reduced in width from baseline to re-entrybetween 1.0 mm and 3.52.7 mm following ARP(p

25] and one was CCT [24]. Healing time varied between 4and 9 months.

Horizontal (bucco-lingual) changes of the AR wereassessed in all four studies. AR width reduction from base-line to re-entry varied between 1.20.9 mm and 2.51.2 mm in the GBR-treated sockets and between 2.62.3 mm and 4.60.3 mm in the control groups. With theexception of one study [23], a statistically significantlysmaller reduction of the alveolar ridge width was observedwhen e-PTFE [24], PGPL [25], or collagen membranes incombination with xenograft [21] were used.

All the four studies investigated the mean change in ARheight at the mid-buccal aspect. The AR height changedfrom baseline to re-entry between +1.32.0 mm and 0.71.4 mm in the ARP groups and between 0.91.6 mmand 3.61.5 mm in the control groups. The resorption inthe ARP group was not statistically significant in three outof four studies [2325]. All studies reported a statisticallysignificantly less post-extraction reduction in AR heightwhen the socket was treated by GBR compared to unassistedhealing.

Vertical dimension changes at mesial and distal aspectsof the socket were measured in two studies [21, 23]. Theobserved differences between baseline and re-entry were notstatistically significant in both groups. In one out of the twostudies the height reduction was statistically significantlysmaller in the test group compared to the control [23].

Two studies captured data on the socket fill [24, 25] andreported statistically significant socket fill in both groupsbetween baseline and re-entry, as well as between tests andcontrols.

No data were found on either initial buccal plate thick-ness or alteration of bone volume. However, one studymeasured the buccal bone thickness loss and reported sta-tistically significantly less reduction in the ARP group [47].

Radiographic measurements

Two RCTs, reporting on 3D radiographic assessment, metthe inclusion criteria [20, 46]. The healing time varied from1 to 4 months. In one study, where the post-extraction socketwas grafted with a radiopaque material (DBBM), treatmentresulted in significantly less reduction in radiographic ARheight compared to unassisted socket healing [46]. The testgroup in the other study, where the higher concentration(1.5 mg/ml) of RhBMP-2 was utilised [20], resulted in amean increase of the radiographic AR width by 3.272.53 mm at the most coronal part, compared to the 0.572.56 mm increase in the group of unassisted healing. ARheight was reduced by 0.021.2 mm in the same test groupand by 1.171.23 mm in the control group (Table 3). Thedifferences between test and control were statisticallysignificant.

Histological results

Eleven studies carried out a histological analysis based ontrephine biopsies retrieved at re-entry [17, 1921, 23, 42,43, 4548]. Seven studies were RCTs [17, 20, 21, 23, 46,47] and four were CCTs [19, 43, 45, 48]. In these studies,ARP was performed in 181 sockets of 158 patients andcompared to 149 sockets that left to heal without anytreatment in 131 patients (Table 4). Only two out ofeight studies reported statistically significantly higher tra-becular bone volume following ARP in comparison to unas-sisted socket healing [21, 42] and two studies reportedstatistically significantly more connective tissue in the post-extraction socket when no ARP was performed [17, 21]. Onthe contrary, one study reported more vital bone in theunassisted socket healing group compared to the ARPgroup [23]. None of the differences of the investigatedhistomorphometric parameters reached statistical signifi-cance in other studies.

Bone grafts Eight studies evaluated histologically thehealing of post-extraction sockets following the applicationof some type of bone grafts/substitutes [17, 19, 42, 43,4548]. Four studies were RCTs [17, 42, 46, 47] and fourwere CCTs [19, 43, 45, 48]. New mineralised bone wasobserved at various levels in all studies in both ARP andcontrol groups in a healing period from 2.5 to 8 months.Connective tissue occupied a portion of the socket in bothgroups. When DFDBA, bioactive glass or DBBM wereused, the graft particles were embedded either in new boneor in connective tissue. In most studies, there was no sig-nificant difference in the type of healing, or amount of boneformation between bone grafts and unassisted sockethealing.

GBR in combination with graft GBR in combination withgraft was utilised in two RCTs. ARP with a collagen mem-brane and deproteinized porcine bone resulted in statisticallysignificantly higher new bone and lower connective tissueformation after 7 to 9 months of healing in comparison tounassisted socket healing [21]. However, residual graftmaterials were present in the ARP biopsies. FDBA andcollagen membrane resulted in similar amounts of new boneformation to untreated sockets, although more vital bonewas observed in the untreated sockets at 4 to 6 months ofhealing (p>0.05) [23].

Biological active material RhBMP-2 in a collagen spongecarrier was completely resorbed at 4 months following ARPregardless of the concentration of the growth factor [20].Mineralised tissue was found and trabecular bone formationwas noticed in two third of both the test and control biopsiesin the RCT.

Clin Oral Invest (2013) 17:341363 347

Adverse events, complications

Adverse events were reported in six RCTs [17, 20, 21, 25,42, 47] and four CCTs [19, 24, 44, 48] including oedema,pain, erythema and membrane exposure/infection. In twostudies, more adverse events, i.e. oedema, erythema [20] ormembrane exposure [24] were observed in the ARP groupcompared to the natural socket healing. No comparisonbetween tests and controls were reported in the other studies(Table 3).

Feasibility of implant placement

Seven studies [17, 19, 23, 42, 45, 46, 48] reported thatimplant placement in the previous sockets were successful,but no differences between the ARP and untreated sites wererevealed. The outcome of implant placement remained un-clear in one article [43] and only re-entry without implanta-tion was performed in three trials [24, 44]. Four studiesreported the need of further augmentation at the stage ofimplant placement. Three of them favoured the ARP groupover the controls, since less [20] or no sites [21, 47] in theARP group presented with residual dehiscence or fenestra-tion defects around the inserted implants (Table 3).

Patient-reported outcome and health economics

No data were found for patient-reported outcome measuresor health economic evaluation.

Quality assessment

Considerable heterogeneity was found among the studies interms of methodological quality. Detailed description of thequality assessment of the included studies is presented inTable 2. Among the 14 included controlled studies, eightwere randomised [17, 20, 21, 23, 25, 42, 46, 47] although infour of them the randomisation technique was not reported[20, 42, 46, 47]. None of the RCTs reported the method ofallocation concealment. Masking of the examiner wasreported at the clinical level in two out of eight [23, 25], atradiological level in one out of two [20] and at histologicallevel in four out of 11 studies [17, 21, 42, 43]. Examinercalibration was declared in three papers [20, 23, 42], whilstinclusion and exclusion criteria were defined in seven pub-lications [17, 21, 23, 42, 43, 46, 47]. Apart from threestudies [21, 43, 46] all the other reported the approval ofthe ethical committee. Three studies were funded by indus-try [17, 20, 44], two studies by academic institution [45, 48]and the remaining nine did not report the source of funding.

Nine trials implemented patient-based analysis [20, 21,2325, 42, 44, 47, 48], whilst the extraction site served asunit of analysis in the rest of the five investigations [17, 19,

43, 45, 46]. Sample size calculations were reported only inthree studies [20, 23, 42], although with insufficient data toevaluate the validity of the calculations. Statistical analysiswas appropriately carried out and described in one studyonly [47]. Appropriate statistics were either not carried out[17, 1921, 43, 45, 46], or the reported data were insuffi-cient to determine the validity [2325, 42, 43, 48]. In addi-tion, no RCTs were either registered with ISRCTN orreported using the CONSORT guidelines (Table 3).

Risk of bias

Four studies were classified as moderate risk of bias [17, 21,23, 25] and the rest were categorised as high risk of bias(Table 2).

Discussion

Key findings

This systematic review has demonstrated that different ARPtechniques do not totally eliminate post-extraction alveolarridge resorption or predictably promote new bone forma-tion. However, the reduction in ridge width and heightfollowing ARP may be less than that which occurs follow-ing natural socket healing. The clinical data suggest that thehorizontal ridge contraction was most successfully limitedin the two studies applying GBR without additional bonegrafts [24, 25], whereas the vertical shrinkage was mostefficiently limited by employing GBR with additional bonegraft [21, 23].

Strengths of the review

The present systematic review was limited to randomisedcontrolled trials, controlled clinical trials and prospectivecohort studies with a control group of empty untreatedsockets. Furthermore, the inclusion criteria of our systematicreview were based on the fact that the clinical merit ofapplying the different ARP techniques could only be vali-dated, if the clinical and histological outcomes following theapplication of a technique are superior to that of unassistedsocket healing.

In comparison to the previous systematic reviews [28,32] the present review has evaluated the histological char-acteristics of the alveolar socket healing with or withoutARP. The amount and the quality of the newly formedosseous tissues in the socket area are essential, especiallywhen the justification of ARP is to facilitate the placementof a dental implant in the position of a previously extractedtooth. It is doubtful, whether an ARP technique should beclaimed successful, if it only preserves the external contour

348 Clin Oral Invest (2013) 17:341363

Table2

Qualityassessmentof

theincluded

studies

Study

QualityCriteria

Estim

ated

risk

ofbias

Firstauthor

Randomisation

Masking

Calibratio

nElig

ibility

Criteria

Followup

Ethicalconsiderations

Funding

Statisticalanalysis

Miscellaneous

Yearof

publication

1.Randomised

1.Therapist

1.Intra-exam

iner

1.Inclusion

criteriadefined

1.Percentage

ofcompleted

follo

wups

1.Ethicsapproval

Sourceof

Funding

1.Appropriate

samplesize

calculationandpower

1.Com

parable

experimentalgroups

2.CONSORT

implem

ented

2.Inform

edconsent

3.ISRCTNregistered

2.Unitof

analysis

4.Other

comments

3.Appropriate

statisticsapplied

2.Exclusion

criteriadefined

2.Adequate

correctio

n

2.Patient

2.Inter-exam

iner

2.Adequate

sequence

generatio

n3.

Examiner

Type

4.Statistician

3.Allo

catio

nconcealm

ent

Reference

number

4.Concealment

adequate

Aimetti

1.Yes

1.N/R

1.Yes

(histo),

N/R

(clin

)1.

Yes

1.N/R

1.Yes

N/R

1.Insufficient

data

todeterm

ine

1.Yes

High

2.N/R

2009

2.N/R

2.N/R

2.N/A

2.Yes

2.N/A

2.Yes

2.Patient

3.N/R

3.Insufficient

data

todeterm

ine

RCT

3.N/R

3.Yes

(histo),

N/R

(clin

).#42

4.N/A

4.N/R

*Reportedas

doubleblind

Anitua

1.Yes

(btw

T-C)

No(w

ithin

T)

1.N/R

1.N/R

1.Yes

1.100%

1.N/R

N/R

1.N/R

1.N/R

High

1999

2.N/A

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

+site

2.N/R

CCT

3.N/R

3.Yes

3.Nostatisticalanalysis

was

carriedout

3.N/R

#43

4.N/A

4.N/R

4.Atsevere

defects

autogenous

bone

was

addedto

PRGF.

Different

healingperiods.

Barone

1.Yes

1.N/R

1.N/R

1.Yes

1.100%

1.N/R

N/R,declared

noconflict

ofinterest

1.N/R

1.Yes

Moderate

2008

2.Yes

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

2.N/R

RCT

3.N/R

3.Yes

(histo),

N/R

(clin

)3.

No

3.N/R

#21

4.N/A

4.N/R

4.Differenthealing

periods.

Cam

argo

N/A

1.N/R

1.N/R

1.Yes

1.100%

1.Yes

Industry

1.N/R

1.N/R

High

2000

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

2.N/R

CCT

3.N/R

3.Insufficient

data

todeterm

ine

3.N/R

#44

4.N/R

Fiorellini

1.Yes

1.N/R

1.N/R

1.No

1.100%

1.Yes

Industry

1.Insufficient

data

1.N/R

High

2005

2.N/R

2.N/R

2.Yes

2.No

2.Unclear

2.Yes

todeterm

ine

2.N/R

RCT

3.N/R

3.Yes

(CTscans)

2.Patient

3.N/R

#20

4.N/A

4.N/R

*Reported

asdouble

blind

3.No

4.Standardisatio

nof

CTscansN/R.

Finalnumber

ofsockets,patients

remainunclear.

Froum

1.Yes

1.N/R

1.N/R

1.Yes

1.100%

1.Yes

Industry

1.N/R

1.N/R

Moderate

2002

2.Yes

2.N/R

2.N/A

2.Yes

2.Unclear

2.Yes

2.Site

2.N/R

RCT

3.N/R

3.Yes

3.No

3.N/R

#17

4.N/A

4.N/R

4.Different

healingperiods.

Enrolmentof

sitesof

subjectsinconsistent.

Clin Oral Invest (2013) 17:341363 349

Table2

(contin

ued)

Study

QualityCriteria

Estim

ated

risk

ofbias

Firstauthor

Randomisation

Masking

Calibratio

nElig

ibility

Criteria

Followup

Ethicalconsiderations

Funding

Statisticalanalysis

Miscellaneous

Yearof

publication

1.Randomised

1.Therapist

1.Intra-exam

iner

1.Inclusion

criteriadefined

1.Percentage

ofcompleted

follo

wups

1.Ethicsapproval

Sourceof

Funding

1.Appropriate

samplesize

calculationandpower

1.Com

parable

experimentalgroups

2.CONSORT

implem

ented

2.Inform

edconsent

3.ISRCTNregistered

2.Unitof

analysis

4.Other

comments

3.Appropriate

statisticsapplied

2.Exclusion

criteriadefined

2.Adequate

correctio

n

2.Patient

2.Inter-exam

iner

2.Adequate

sequence

generatio

n3.

Examiner

Type

4.Statistician

3.Allo

catio

nconcealm

ent

Reference

number

4.Concealment

adequate

Guarnieri

N/A

1.N/R

1.N/R

1.Yes

1.N/R

1.Yes

Governm

ent;

institu

tion

1.N/R

1.N/R

High

2004

2.N/R

2.N/A

2.No

2.N/A

2.Yes

2.Site

2.N/R

CCT

3.N/R

3.No

3.N/R

#45

4.N/R

Iasella

1.Yes

1.N/R

1.Yes

1.Yes

1.100%

1.Yes

N/R

1.Insufficient

data

todeterm

ine

1.Yes

Moderate

2003

2.Yes

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

2.N/R

RCT

3.N/R

3.Yes

3.Insufficient

data

todeterm

ine

3.N/R

#23

4.N/A

4.N/R

Lekovic

N/A

1.N/R

1.N/R

1.No

1.70%

(premature

exposure

ofe-PTFE

barrierin

3/10)

1.Yes

N/R

1.N/R

1.Yes

High

1997

2.N/R

2.N/A

2.No

2.N/R

2.Patient

2.N/R

CCT

3.N/R

2.Yes

3.Insufficient

data

todeterm

ine

3.N/R

#24

4.N/R

Lekovic

1.Yes

1.N/R

1.N/R

1.No

1.100%

1.Yes

N/R

1.N/R

1.Yes

Moderate

1998

2.Yes

2.N/R

2.N/A

2.No

2.Yes

2.Yes

2.Patient

2.N/R

RCT

3.N/R

3.Yes

3.Insufficient

data

todeterm

ine

3.N/R

#25

4.N/A

4.Yes

Nevins

1.Yes

1.N/R

1.N/R

1.Yes

1.100%

1.N/R

N/R

1.N/R

1.Yes

High

2006

2.N/R

2.N/R

2.N/A

2.Yes

2.Yes

2.N/R

2.Site

2.N/R

RCT

3.N/R

3.N/R

3.No

3.N/R

#46

4.N/A

4.N/R

4.Standardisationof

CT

scansN/R.Testm

aterial

radiopaque.D

ifferent

healingperiods.

Pelegrine

1.Yes

1.N/R

1.N/R

1.Yes

1.100%

1.Yes

N/R

1.N/R

1.N/R

High

2010

2.N/R

2.N/R

2.N/A

2.Yes

2.Yes

2.Yes

2.Patient

2.N/R

RCT

3.N/R

3.N/R

3.Yes

3.N/R

#47

4.N/A

4.N/R

Serino

N/A

1.N/R

1.N/R

1.Yes

1.80%

1.Yes

N/R

1.N/R

1.N/R

High

2003

2.N/R

2.N/A

2.No

2.Unclear

2.Yes

2.Site

2.N/R

CCT

3.N/R

3.No

3.N/R

#19

4.N/R

4.Molarsonly

inT.

350 Clin Oral Invest (2013) 17:341363

of the AR, but the newly formed tissue is of inferior qualityand quantity (percentage of matured trabecular bone) towhat is normally achieved following a tooth extraction.

Finally, the quality of the included studies has also beenmeticulously assessed in this review. Such a quality evalu-ation of the retrieved data is essential to estimate the sourceand magnitude of potential bias that may lead to delusiveconclusions.

Strength of evidencerisk of bias

The quality assessment of the included studies in this sys-tematic review revealed that none of the trials have qualifiedfor a low risk of bias category. Ten out of the 14 studiespresented with high risk of bias thus their results must beevaluated with caution. The lack of clear reporting of re-search methodology elements, such as adequate randomiza-tion and concealment and/or masking of the therapist andthe examiner were among the primary reasons for the highrisk of bias [49]. We did not contact authors for clarificationof unclear methodology. Therefore, it is possible that actualstudy conduct was better than that reported in the publica-tion. Statistical considerations played important role as well,since appropriate analytical statistics was completed andreported merely in one study [47]. Power calculation wasconducted in three trials only [21, 23, 42], nevertheless thereported data were insufficient to determine the validity ofthe calculation.

Dimensional changes and histological characteristics

Sufficient ridge width and height have been considered asone of the key requirements for successful implant therapyand for the establishment of an aesthetically pleasing emer-gence profile at fixed partial dentures [8, 50, 51]. Therefore,the alterations in oro-facial (horizontal) and apico-coronal(vertical) AR dimensions were selected as the primary out-comes of the present review. Direct intra-surgical measure-ments on the AR at re-entry are considered as the mostprecise method to evaluate the bone volume changes fol-lowing ARP. It is desirable though to establish and validate asurrogate measure that avoids the need for re-entry surgery,while providing the clinician with a reliable measure. Two-dimensional radiographs, such as periapical or panoramicradiographs, are not ideal to estimate the 3D changes of theAR [52]. Also, measurements of the alveolar mucosa levelor study casts incorporate not only the alveolar bone, butalso the overlaying soft tissue. For these reasons onlystudies performing clinical or 3D radiographic evaluationof hard tissue were included in this review. Cone-beamcomputerised tomography (CBCT) appears to offer a validtechnique to assess alveolar ridge changes, with newer mod-els greatly reducing radiation exposure [53]. However, aTa

ble2

(contin

ued)

Study

QualityCriteria

Estim

ated

risk

ofbias

Firstauthor

Randomisation

Masking

Calibratio

nElig

ibility

Criteria

Followup

Ethicalconsiderations

Funding

Statisticalanalysis

Miscellaneous

Yearof

publication

1.Randomised

1.Therapist

1.Intra-exam

iner

1.Inclusion

criteriadefined

1.Percentage

ofcompleted

follo

wups

1.Ethicsapproval

Sourceof

Funding

1.Appropriate

samplesize

calculationandpower

1.Com

parable

experimentalgroups

2.CONSORT

implem

ented

2.Inform

edconsent

3.ISRCTNregistered

2.Unitof

analysis

4.Other

comments

3.Appropriate

statisticsapplied

2.Exclusion

criteriadefined

2.Adequate

correctio

n

2.Patient

2.Inter-exam

iner

2.Adequate

sequence

generatio

n3.

Examiner

Type

4.Statistician

3.Allo

catio

nconcealm

ent

Reference

number

4.Concealment

adequate

Serino

N/A

1.N/R

1.N/R

1.Yes

1.80%

1.Yes

Governm

ent;

institu

tion

1.N/R

1.N/R

High

2.Patient

2.N/R

3.Insufficient

data

todeterm

ine

3.N/R

2008

2.N/R

2.N/A

2.No

2.Unclear

2.Yes

CCT

#48

3.N/R

4.N/R

N/A

notapplicable;N/R

notreported,Ttest;Ccontrol;RCTrandom

ised

controlledtrial;CCTcontrolledclinical

trial;PRGFplatelet-richgrow

thfactor;CONSO

RTConsolid

ated

Standards

ofReportin

gTrials;ISRCTNInternationalStandardRandomised

ControlledTrialNum

berRegister

Clin Oral Invest (2013) 17:341363 351

Table3

Firstauthor

Trial

characteristics

Population

characteristics

Confounding

factors

Defect

characteristics

Testmaterial

(num

berof

sockets/

subjects)

Control

(num

berof

sockets/

subjects)

Surgical

managem

ent

Follow-up

Alveolarridge

dimension

changesin

horizontal

width

Alveolarridge

dimension

changesin

vertical

height

Implant

1.Feasibility

ofim

plant

placem

ent

2.Necessityof

simultaneous

augm

entation

Mean/medianmm

(reference

point)

Mean/medianmm

1.Whole

ridge

1.Mid-buccal

1.Healin

gperiod

Year

ofpublication

2.Buccalplate

2.Mesial

1.Socket

locatio

n1.

Type

offlap

3.Distal

2.Num

ber

ofdrop-outs

4.SocketFill

2.Softtissue

closure

2.Defect

morphology

1.Country

1.Age

range

(mean)

inyears

1.Smoking

3.Adverse

events

3.Postoperativ

eantim

icrobials

2.Num

berof

centres

2.Periodontitis

Type

Design

2.Num

berof

patients

(sockets)

3.Settin

gMethodology

Reference

number

Aimetti

1.Italy

1.36-68

(51.27

8.4)

1.No

1.Maxillary

anterior

Calcium

sulphate

Empty

(18/18)

1.Flapless

1.3months

1.T:-2.01.1**

1.T:-0.51.1*,

C:-1.20.6**,***

1.Im

plants

were

inserted

2009

2.1

RCT

Parallel

2.N/R

3.University

Clin

+Histo

Hem

ihydrate

(22/22)

#42

2.40

(40)

2.Noprim

ary

closure

2.4-wall

configuration

2.N/R

C:-3.21.8**,

***

3.Uneventful

healing

3.Amoxicillin

2g/day

for

5days,

Chlorexidine

0.12%

for

2weeks

2.N/R

2.T:-0.20.6,

C:-0.50.9

3.T:-0.40.9,

C:-0.51.1

4.T:

11.32.8**,

C:10.02.3**

(Acrylicstent)

2.N/R

Anitua1999

1.Spain

1.T:35-55

(41)

1.Yes

1.Any

T1:

PRGF

(5+3/5+3)

Empty

(10+3/

10+3)

1.Full-thickness

1.2.54

months

N/A

N/A

1.N/R

2.N/R

2.Variable

2.Yes

2.Primary

closure

2.0

3.N/R

T2:

PRGF+

Autologous

bone

(5/5)

3.Amoxicillin

1.5g/day

for

5days

2.1

C:38-54(42)

CCT

3.Private

practice

2.23

(26)

Parallel+Split-

mouth

Histo

#43

Barone

2008

1.Italy

1.26-69

1.C)

4.N/R

(T1vs

T2/C)***

3.Penicillin

(?mg)

for7-10

days+

Chlorexidine

0.12%

T3:

Collagen

sponge

(?/17?)

2.5

0%buccalbone

loss

2.8centres

2.80

(95)

2.N/R

RCT

3.University

Parallel

Radiogr+

Histo

#20

Froum 2002

1.USA

1.35-77

(54.911.9)

1.No

1.Any

T1:

Bioactiv

eglass(10/8)

Empty

(10/10)

1.Full-thickness

with

outvertical

incisions

1.6-8months

N/A

N/A

1.Anim

plant

ofappropriate

size

was

placed

inthehealed

sockets.

2.0

3.Uneventful

healing

T2:

DFDBA

(10/8)

2.Primary

closure

2.N/R

3.Doxycyclin

e100m

g/day

for13

days+

Chlorexidine

0.12%

for

30days

2.N/R

2.4-wall

configuration,

2mm

buccal

plateloss

2.19

(30)

2.Single

centre

RCT

Splitmouth

3.University

Histo

#17

Guarnieri

2004

1.Italy

1.35-58

1.N/R

1.Maxillary,

mandibular

anteriors,

prem

olars

Calcium

sulphate

Empty

(5/5)

1.Full-thickness

with

outvertical

incisions

1.3months

N/A

N/A

1.Bucco-lingual

dimensionsof

thealveolar

ridge

enabled

safeinsertion

oftitanium

implant.

2.socketwith

ridge

resorptio

n5

0%were

excluded

2.Primaryclosure

3.Amoxicillin

(?mg)

for

1week+Chlorexidine

0.2%

for2weeks

2.N/R

Hem

ihydrate

(10/10)

2.N/R

2.Yes

3.N/R

2.10

(25)

2.N/R

3.N/R

CCT

Parallel+

Split

mouth

Histo

#45

Iasella

2003

1.USA

1.28-76

(51.513.6)

1.Yes

1.Maxillary

anteriors,

prem

olars

and

mandibular

prem

olars

Tetracycline

hydrated

FDBA+

Empty

(12/12)

1.Full-thickness

with

outvertical

incisions

1.4or

6months

(com

bined)

1.T:-1.20.9*,

C:-2.62.3*

1.T:

+1.32.0,

C:-0.91.6***

1.Im

plants

successfully

placed

atall

sites

2.N/R

2.N/R

2.T:

-0.10.7,

C:-1.00.8***

2.Somesiteshad

slightdehiscence

andrequired

further

augm

entation

2.Noprim

aryclosure

2.N/R

3.T:

-0.10.7,

C:-0.80.8***

3.Doxycyclin

200m

g/dayfor

1week+

Chlorexidine

0.12%

for

2weeks

collagen

mem

brane

(12/12)

2.0

4.N/R

3.N/R

(Acrylicstent)

3.N/R

2.24

(24)

RCT

2.N/R

Parallel

Clin

+Histo

#23

Clin Oral Invest (2013) 17:341363 353

Table3

(contin

ued)

Firstauthor

Trial

characteristics

Population

characteristics

Confounding

factors

Defect

characteristics

Testmaterial

(num

berof

sockets/

subjects)

Control

(num

berof

sockets/

subjects)

Surgical

managem

ent

Follow-up

Alveolarridge

dimension

changesin

horizontal

width

Alveolarridge

dimension

changesin

vertical

height

Implant

1.Feasibility

ofim

plant

placem

ent

2.Necessityof

simultaneous

augm

entation

Mean/medianmm

(reference

point)

Mean/medianmm

1.Whole

ridge

1.Mid-buccal

1.Healin

gperiod

Year

ofpublication

2.Buccalplate

2.Mesial

1.Socket

locatio

n1.

Typeof

flap

3.Distal

2.Num

ber

ofdrop-outs

4.SocketFill

2.Softtissue

closure

2.Defect

morphology

1.Country

1.Age

range

(mean)

inyears

1.Smoking

3.Adverse

events

3.Postoperativ

eantim

icrobials

2.Num

berof

centres

2.Periodontitis

Type

Design

2.Num

berof

patients

(sockets)

3.Settin

gMethodology

Reference

number

Lekovic

1997

1.Yugoslavia

/USA

1.(49.8)

1.N/R

1.Maxillary

and

mandibular

anteriors,

prem

olars

e-PTFE

mem

brane

(10/10)

Empty

(10/10)

1.Full-thickness

with

4vertical

releasing

incisions

1.6months

1.10/10:,

T:-1.800.51,

C:-4.400.61**,

***

1.10/10:

T:-0.50.22,

C:-1.20.13**,

***

1.Reentry

only

7/10:T:-1.710.75,

C:-4.430.72**,

***

7/10:

T:-0.280.18,

C:-1.00.0**,

***

3/10:T:-2.000.00,

C:-4.330.88*

3/10:T:-1.00.58,

C:-1.660.33

(titanium

tack)

2.N/R

3.N/R

4.10/10:

T:4.90.86*,

C:3.00.63,

***

2.N/R

7/10:T

:5.431.1*,

C:2.921.61,***

3/10:T

:3.661.20,

C:4.331.45

(tobuccalbone

crest)

2.Primaryclosure

3.Penicillin

1g/day

for

7days+

Chlorexidine

0.2%

2.N/A

2.3/10

drop-outs

dueto

prem

ature

mem

brane

exposure

3.3/10

exposed,

7/10

noinfection

2.10

(20)

2.N/R

CCT

2.N/R

(presumably

singlecentre)

Split-mouth

2.N/R

Clin

3.University

#24

Lekovic

1998

1.Yugoslavia

1.(52.611.8)

1.N/R

1.Maxillary

and

mandibular

anteriors,

prem

olars

PG/PL

mem

brane

(16/16)

Empty

(16/16)

1.Full-thickness

with

4vertical

releasingincisions

1.6months

1.T:-1.310.24*

1.T:-0.38

0.22,

C:-1.50

0.26*,

***(titanium

tack)

1.Reentry

only

2.N/A

2.0

C:-4.56

0.33*,

***

3.Uneventful

healing

2.N/R

2.Primaryclosure

2.N/R

3.Penicillin1g/day

for7days+

Chlorexidine0.12%

for2weeks

3.N/R

2.Yes

(treated)

2.N/R

4.T:5.81

0.29*,

C:3.94

0.35*,

***

(tobuccalbone

crest)

2.16

(32)

2.1

3.University

RCT

Split-mouth

Clin

#25

Nevins2006

1.USA/Italy

1.N/R

1.N/R

1.Maxillaryanterior

DBBM

(19/9)

Empty(17/9)

1.Partial

thickness

1.13months

(biopsiesat6M

)N/A

1.T:-2.422.58,

C:-5.243.72***

1.Im

plantswere

placed,but

number

unknow

n

2.Buccalplatewas

comprom

ised

2.Primary

closure

2.0

3.N/R

2.N/R

2.N/R

3.N/R

3.N/R

4.N/R

(At6mm

ridgewidth)

2.Yes

RCT

2.N/R

Split-mouth

3.N/R

Radiogr+

Histo

#46

2.9(36)

354 Clin Oral Invest (2013) 17:341363

Table3

(contin

ued)

Firstauthor

Trial

characteristics

Population

characteristics

Confounding

factors

Defect

characteristics

Testmaterial

(num

berof

sockets/

subjects)

Control

(num

berof

sockets/

subjects)

Surgical

managem

ent

Follow-up

Alveolarridge

dimension

changesin

horizontal

width

Alveolarridge

dimension

changesin

vertical

height

Implant

1.Feasibility

ofim

plant

placem

ent

2.Necessityof

simultaneous

augm

entation

Mean/medianmm

(reference

point)

Mean/medianmm

1.Whole

ridge

1.Mid-buccal

1.Healin

gperiod

Year

ofpublication

2.Buccalplate

2.Mesial

1.Socket

locatio

n1.

Typeof

flap

3.Distal

2.Num

ber

ofdrop-outs

4.SocketFill

2.Softtissue

closure

2.Defect

morphology

1.Country

1.Age

range

(mean)

inyears

1.Smoking

3.Adverse

events

3.Postoperativ

eantim

icrobials

2.Num

berof

centres

2.Periodontitis

Type

Design

2.Num

berof

patients

(sockets)

3.Settin

gMethodology

Reference

number

Pelegrine

2010

1.Brazil

1.28-70

(47.510.3)

1.No

1.Maxillary

anteriors

Autologous

bone

marrow

(15/7)

Empty

(15/6)

1.Full-thickness

with

2buccal

verticalreleasing

incisions

1.6months

1.T:-1.0*,

C:-2.5*,***

1.T:

-0.5*,

C:-1.0*,***

(Titanium

screw)

1.Allimplants

osseointegrated

2.N/R

2.13

(30)

2.N/R

2.Primaryclosure

3.N/R

2.1

2.0

3.University

2.T:-0.75,

C:-1.75,***

4.T:10.33*,C:10.32*

(tobuccalbone

crest)

2.T:with

out

further

augm

entatio

n,C:At5sites

augm

entatio

nor

expansion

carriedout

3.N/R

3.Uneventful

healing

RCT

2.Socketswith

severe

bone

loss

were

excluded

Parallel

Clin

+histo

#47

Serino

2003

1.Italy

1.35-64

1.N/R

1.Any

PG/PLsponge

(26/24)after

drop-out

Empty

(13/12)

afterdrop-out

1.Full-thickness

buccally

and

lingually

1.6months

N/A

1.T:+1.31.9*,

C:-0.81.6

1.Placementof

implantsin

all

CandTsites

with

good

prim

arystability

2.Buccalplate

couldbe

partially

orcompletely

lost

2.1

CCT

Parallel+

split-m

outh

2.45

(39)

before

drop-out

3.N/R

2.Yes

(treated)

Clin

+Histo

#19

2.Noprimary

closure

2.9drop-outs

forreasons

unrelatedto

thetherapy

2.T:-0.21.0,

C:-0.61.0

3.T:-0.11.1,

C:-0.81.5

3.No

antib

iotics;

Chlorexidine

0.2%

for

2weeks

3.Uneventful

healing

4.N/R

(Acrylicstent)

2.N/R

Serino

2008

1.Italy

1.32-64

1.N/R

1.Any

non-molars

PG/PLsponge

(7/7)

Empty(9/9)

afterdrop-out

1.Full-thickness

buccally

and

lingually

1.3months

N/A

N/A

1.Placementof

implantsin

all

CandTsites

with

good

prim

arystability

2.1

2.Yes

(treated)

2.4drop-outs

forreasons

unrelatedto

thetherapy

afterdrop-out

CCT

2.Alveolar

bone

height

8mm

2.Noprim

ary

closure

Parallel

2.N/R

Histo

3.NoAntibiotics;

Chlorexidine

0.2%

for2weeks

3.Uneventful

healing

2.20

(20)

before

drop-out

#48

3.N/R

*p