The Effects of Alveolar Ridge Preservation: A Meta-Analysis Maximillian Willenbacher, DMD;* Bilal Al-Nawas, MD, DMD;* Manfred Berres, mathematician;†‡ Peer W Kämmerer, MD, DMD;§ Eik Schiegnitz, MD, DMD*

ABSTRACT Purpose: The aim of this article was to analyze the horizontal, vertical, and histological effects of alveolar ridge preservation (ARP) versus the ones of unassisted socket healing, in the format of an up-to-date review and meta-analysis. Materials and Methods: An extensive electronic search in the electronic databases of the National Library of Medicine was conducted for articles published up to June 2014 to identify literature presenting data on the topic of ARP. Only randomized controlled trials, controlled clinical trials, and prospective trials were included for meta-analysis. Results: After screening 903 abstracts from the electronic database, we included 64 studies in qualitative and 18 in quantitative synthesis. Quality assessment characterized a medium risk of bias for the included literature. The meta-analysis showed a mean difference between test and control groups of approximately 1.31 to 1.54 mm in bucco-oral bone width and 0.91 to 1.12 mm in bone height. Additionally, the intergroup difference in percentage of vital bone was assessed to be inconclusive across the included studies. Implants could be inserted into the determined position without further augmentation in 90.1% of the experimental sites, while this was the case in only 79.2% of the control sockets. Conclusions: Resorption of the alveolar ridge cannot be totally stopped by ARP, while it still can be prevented compared with unassisted healing. No reliable predictions on the histological effects could be made due to limited data. Further on, no recommendation for a specific technique of ARP could be made. In conclusion, there is still need for ongoing research on the topic, even though the lower percentage of implant sites that needed additional augmentation in test sockets seemed to bring a patient benefit. KEY WORDS: alveolar ridge preservation, bone augmentation procedures, bone substitute materials, dental implants, meta-analysis, oral implants, socket healing

INTRODUCTION *Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre of the Johannes Gutenberg-University, Mainz, Germany; †Department of Mathematics and Technology, University of Applied Sciences Koblenz, RheinAhrCampus Remagen, Remagen, Germany; ‡Institute of Medical Biometry, Epidemiology, and Informatics, Johannes Gutenberg-University, Mainz, Germany; §Department of Oral and Maxillofacial Surgery, Plastic Surgery, University of Rostock, Rostock, Germany

In adults, teeth get lost for various reasons, like periodontal disease, trauma, periapical lesions, or other pathological effects. After extraction, not only the tooth is lost, but also the alveolar socket passes a huge remodeling process, which has been associated with further bone loss.1–5 Alveolar socket resorption results in approximately 3.87-mm loss of width and 1.67 to 2.03-mm loss of height primarily in the first 3 months.5 This does not only generate aesthetical problems, it also limits the feasibility of dental implants and fixed partial dentures.6–8 Absorption is affected by multiple factors, like depth of the extraction socket, mucosa thickness, metabolical factors, and functional loading.1 Preventing these factors alone does not sufficiently help to stop ridge resorption. Therefore, further techniques are necessary.

Corresponding Author: Dr. Eik Schiegnitz, Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre of the Johannes Gutenberg-University, Augustusplatz 2, Mainz 55131, Germany; e-mail: [email protected] There are no commercial or other associations that might create a duality of interests in connection with the article. The data from this study are part of the dissertation work submitted to Johannes Gutenberg University, Mainz, as part of doctoral thesis of Maximillian Willenbacher. © 2015 Wiley Periodicals, Inc. DOI 10.1111/cid.12364

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In literature, many strategies like ultrasound therapy,9 sandwich osteotomy,10,11 and distraction osteogenesis12 have been described to prevent (e.g., ultrasound therapy) or reconstruct (e.g., sandwich osteotomy, distraction osteogenesis) ridge resorption. None of them could fit the desired purpose of presenting a suitable ridge height and width for further implant or prosthetic treatment with a minimum effort. Alveolar socket preservation (ASP) and alveolar ridge preservation (ARP) may seem to be a reliable alternative. In terms of definition, ASP is only used for a technique in which a completely contained extraction sockets are filled with a bone substitute material (BSM) and/or sealed with membranes, whereas in ARP, damaged extraction sockets are also included. As in this article sockets without and sockets with minor damages are included from this point on, it is only spoken of ARP. However, it should be clear that the term preservation does not mean that the alveolus original dimension can be kept. It is much more an attempt to keep the bone loss as low as possible. ARP has been realized in many well-documented trials with different kinds of BSM. Those BSM can be roughly divided into four groups, which are autografts (from the same patient), allografts (from the same species), xenografts (from another species), and alloplastic materials (synthetic materials). Among the described substitutes in this article are autologous bone (AB) and bone marrow grafts13,14; different allografts like demineralized freeze-dried bone allograft (DFDBA), mineralized freeze-dried bone allograft (FDBA)15–17; xenografts like deproteinized bovine bone mineral (DBBM), absorbable collagen sponges, or corticocancellous porcine bone18–21; alloplast materials like bioactive glass particles; and different kinds of calcium phosphates15,19,21–25 and bioactive materials like recombinant human bone morphogenetic protein-2 (rhBMP-2) and platelet-rich fibrin (PRF).26,27 Another advantage to ARP is the additional use of membranes, which is described in the procedure of guided bone regeneration (GBR).13,16,18–21,28,29 All of the above treatments for ARP have been shown to work well in clinical trials and case reports. Still, the question remains: How much does socket preservation help in the means of dimensional changes and histological bone quality? What are the actual effects of ARP? And which is the most effective BSM/technique for this procedure?

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To answer these questions, in the last few years, a couple of reviews on ARP have been written.30–35 However, none of the above reviews included either studies later than 201230–33,35 or studies with data for teeth unrelated to the aesthetic zone.34 As a consequence, the aim of the current study was to analyze the horizontal and vertical changes as well as the histology of sites with unassisted socket healing versus ARP, in the format of an up-to-date review and meta-analysis. MATERIALS AND METHODS Protocol Development and Outcomes Variables The study protocol was developed according to the Preferred Reporting Items for Systematic Review and MetaAnalyses statement.36 The following focused question in the Patient, Intervention, Comparison, and Outcome format was used37: “How much do ridge dimension and histology of fresh extraction sockets alternate in different kinds of ARP compared to unassisted socket healing?” Primary outcomes of this study were the horizontal (bucco-oral) ridge dimension changes, the vertical (apico-coronal) ridge dimension changes on a mid-buccal reference point between the tooth extraction and the point of follow-up, as well as the percentage of vital bone in a histological core, which was yielded at the time of implantation. Secondary outcomes included changes in the thickness of the buccal plate; vertical dimension changes on a mesial and a distal reference point and the socket fill (from lowest point of the alveolus to the bone crest); the achievability of the targeted implant position without further augmentation; and the implant survival as well as the percentage of connective tissue and the percentage of residual BSM in the histological bone core. Inclusion/Exclusion Criteria Inclusion Criteria 1. Studies reporting on a test group underwent one of the following interventions: socket grafting with any BSM; GBR with resorbable/nonresorbable barriers or soft tissue graft; or biological active materials; and combinations of the above techniques or materials, whereas the control group underwent unassisted socket healing. 2. Studies on humans, in which only healthy individuals participated

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3. Studies reporting on a minimum of five sockets per group and 20 sockets overall (the minimum number of study subjects was set in sockets instead of patients because this was the commonly described parameter, which was given in all studies and treatment groups) 4. Studies performing at least one of the following measurement methods: clinical measurement or three-dimensional radiographic evaluation or histological examination 5. Studies published in English

Search Strategy Before any literature research was performed, the authors of this article reflected on how to extract those publications that met the topic of the review. Therefore, the previously stated “focused question” and “criteria for inclusion and exclusion” were committed and discussed. Following this, a list of search terms was generated and MeSH-Terms were added, which resulted in these keywords: (“prospective” OR “RCT” OR “CCT” OR “retrospective”) AND (“tooth extraction” OR “tooth removal” OR “socket” OR “alveol” OR “ridge” OR “fresh extraction socket” OR “alveolar socket” OR “tooth socket” OR “alveolar bone loss” OR “bone resorption” OR “bone remodeling”) AND (“preserve” OR “reconstruct” OR “augment” OR “fill” OR “seal” OR “graft” OR “repair” OR “membrane” OR “alveolar ridge preservation” OR “barrier” OR “bone regeneration” OR “bone substitutes” OR “transplantation”) NOT (“trauma” OR “tumor” OR

3

TABLE 1 Summary of Excluded Studies Reason of Exclusion

No control group

Studies 10,12,46,57–66 11,41,44,47,67–78

Retrospective Case report Study did not address the intended question Not enough patients Patient assembly did not match the inclusion/ exclusion criteria (simultaneous placement of implants, sinus augmentation, extraction of third molars) Declaration of values was not comparable (values in %, no fitting p values were found, different measurement methods) Study on animals

Exclusion Criteria 1. Case reports, case series, and retrospective analyses were excluded. 2. Studies on ill patients (e.g., uncontrolled diabetes mellitus, cleft lip and palate, or cancer) or patients that lost their tooth by injury were excluded. 3. Studies reporting on immediate placement of dental implants were excluded. 4. Studies describing extraction of third molars were excluded. 5. Studies in which sinus augmentation was assessed were excluded. 6. Studies that used two-dimensional radiography as their prime method of measurements 7. Studies or study-arms reporting on p values, which were described not to be significant, were excluded.

Alveolar Ridge Preservation

57,58,64 44,59,79,80 9,10,12,42,72,81–84 11,43,47,62,85 42,81,82,86–88

89–91

92

“injuries” OR “cancer” OR “cleft lip and palate” OR “immediate implant” OR “third molar” OR “wisdom tooth” OR “case study” OR “case report”). With this list, an excessive literature research was accomplished using the MEDLINE/PubMed database. Additionally, the literature of other reviews was compared, and relevant articles not yet included were hand-searched and added. Literature was reviewed up to June 11, 2014. The publications excluded in this step are listed in Table 1 and could partly be used for qualitative statements as well. Risk of Bias/Quality Assessment In order to assess the quality of the given articles, a similar method was chosen to the one described by Vignoletti and colleagues,33 in which the quality of the included articles was classified according to the Cochrane statements, the CONSORT statements, the MOOSE statement, the STROBE statements, and further recommendations. Therefore, the studies were inspected for the following six criteria: • • • •

• •

Randomization Blinding of the patient and/or the examiner Definition of inclusion and exclusion criteria Selection of a representative population group (at least 20 patients overall and 10 sockets in each group) Reporting of the follow-up and reasons for dropout Identical treatment between groups except for the intervention

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Studies were then categorized into groups of low potential risk of bias, if all of the above criteria were fulfilled. As moderate risk of bias, if one of the criteria did not match, and as a high potential risk of bias if two or more of the criteria were missing. Meta-Analysis/Statistical Methods As outcomes for the meta-analysis, the mean horizontal alveolar ridge (MHAR) dimension changes of the whole ridge, the mean vertical alveolar ridge (MVAR) dimension changes on a midbuccal reference point, and the percentage of vital bone in the histological probe (Histo) were determined. As the test of heterogeneity resulted in a p value of p < .0001 a random effects model seemed suitable. The DerSimonian and Laird method for estimating the between-study variance38 was applied using the package “meta” of the open source program r.39 Since the calculations needed a standard deviation (SD), two studies without SD21,27 needed to be excluded for meta-analysis in the MHAR group. Another study in the Histo-group15 also did not present SD, but in that case, the pooled SD could be calculated from the means and the F statistic which was implicitly given by the exact p value. For this reason, the study could be included in the analysis. Another flaw was the fact that some studies included up to three test arms that were only compared with one control. In these cases, information from the controls was equally distributed to the test groups by assuming that each of, say, three test groups had its own control of one-third of the observations of the control and the mean and standard deviation of the actual control group. This was assumed not to produce a systematic error but still gives results that are imprecise. To give a more precise result, another meta-analysis for each value was repeated, where only two armed studies were allowed. Also, the spread of follow-ups (between 2 and 9 months) seemed to produce rather incomparable results. Therefore, a second set of meta-analysis focusing only on studies with a follow-up of 6 1 1 months was included. Due to a low number of studies with histological outcomes, no meta-analysis could be performed on only two-armed studies with a follow-up of 6 1 1 months. RESULTS Study Selection and Study Characteristics The previously described search strategy resulted in 903 identified records after applying the filters (figure 1).

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After a first and second approach of selection by title and abstract, 64 articles remained to be downloaded and evaluated in full text. Forty-six studies needed to be excluded as seen in Table 1. The 18 included articles contained three controlled clinical trials (CCTs) and 14 randomised controlled clinical trial (RCTs) plus one cohort study. All articles reported on the effects of different ARP techniques by either clinically or 3D-radiographically (computer tomography or digital volume tomography) measuring the alveolar height and width before ARP and after the follow-up. During reentry for implant placement also, trephine biopsies were taken and histologically evaluated in six studies (Table 2). Concerning the applied technique used for ARP, the following three groups could be categorized: (1) BSM: autograft,13,14 allograft,15–17 xenograft,18–21,40 and alloplastic15,19,21–25; (2) GBR: GBR alone28,29 or GBR with BSM13,16,18–21; and (3) bioactive material.26,27 Quality Assessment/Risk of Bias The evaluation of quality showed a huge variety across studies. A detailed list of qualitative criteria for each article is given in Table 3. Ten studies reported on a blinding, of which six were single blinded,15,16,18,20,27,40 mostly to the examiner, and four were double blinded.17,25,26,29 But only one study specifically reported a patient blinding.26 All articles answered an appropriate and clearly focused question and treated the different groups identical except for the intervention. Only two studies did not define an inclusion and exclusion criteria,26,28 and three others did not exactly name the criteria for exclusion.13,23,24 Additionally, the reporting of follow-up was completed for all trials. Still, five studies accounted dropouts with reasons for dropout.17,21,23,24,28 The source of funding was given in nine of the articles. Mostly the source of funding was industrial. No conflicts of interest were claimed in all industrial-founded trials, except for the one of Fiorellini and colleagues.26 After assessing the data, five papers had a low risk of bias,16–18,25,40 and six papers had a moderate risk of bias.15,19,20,26,27,29 The rest was presented with a high risk (Figure 2). Primary Outcomes of the Studies by Intervention Group Overall, 18 articles including 527 patients and 608 sockets were reviewed. The sockets were unevenly distributed between test (368 sockets) and control

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Alveolar Ridge Preservation

5

Figure 1 PRISMA flow diagram.

group (240 sockets). The MHAR dimension changes of the whole ridge ranged from −6.10 1 2.50 to 3.27 1 2.53 mm in test groups and from −4.56 1 0.33 to 1.30 1 1.00 mm in the group of unassisted socket healing. The mean vertical (MVAR) dimension at a midbuccal point changed, ranging from −2.00 1 2.40 up to 1.30 1 1.90 mm in test groups, while the range was from −3.60 1 1.50 to 1.20 1 0.40 mm in the controls. Finally, the range of the primary histological outcome parameter (% of vital bone) went from 28 1 14% to 66%, whereas the range in the control group only accounted 25.70 1 9.50% to 54 1 12%. To give a better understanding of the many outcomes in the evaluated articles, studies were assessed, and the outcomes were compared in the different groups of intervention. BSM-Autograft. Both articles on autografts were RCTs and included 50 sockets (25 test/25 control). One of them used autologous bone (AB) combined with a titanium mash in the manner of GBR,13 and the other one used a bone marrow graft.14 Both studies measured the

horizontal bone loss of the whole ridge, while only Pelegrine and colleagues14 showed significantly less reduction in the test group (−1.14 1 0.87 mm) than in the control group (−2.46 1 0.40 mm; p = .014). Further on the vertical bone reduction on a midbuccal reference point was only measured in one of the two studies. In that article the reduction was bigger in the control group (−1.17 1 0.26 mm) than in the test group (−0.62 1 0.51 mm; p = .016). The primary histological outcome of percentage of vital bone was only assessed in the same trial of Pelegrine and colleagues14 and showed that there was more vital bone in the BSM group 45.47 1 7.21% than in the group of unassisted healing 42.87 1 11.33% (p = .36) after 6 months. BSM-Allograft. In three articles, allografts were used to treat 32 sockets. Thirty-two sockets were left to heal on their own. The different utilized allografts were: demineralize freeze-dried bone allograft (DFDBA),15 freezedried bone allograft (FDBA),16 or demineralized bone allograft (DBA) paste.17 Only two studies for each

Max anteriors and premolars/NA

Max anteriors and premolars + mand premolars/NA

Any/defects with partial or complete loss of buccal wall included

Max anteriors and premolars/only with more than 50% buccal bone loss

Max anteriors and premolars/NA

Max and mand anteriors and premolars/only four-wall defects

Clin.

Clin.

Clin. + Histo

Clin. + Histo

Radiogr. + Histo

Clin.

Clin. + Histo

RCT

CCT

RCT

CCT

RCT (cohort study)

RCT

RCT

Lekovic and colleagues 199829

Camargo and colleagues 200022

Iasella and colleagues 200316

Serino and colleagues 200323

Fiorellini and colleagues 200526

Pinho and colleagues 200613

Barone and colleagues 200818

Anteriors and premolars/NA

Anteriors and premolars/NA

Clin.

CCT

Defect Location/ Defect Type

Lekovic and colleagues 199728

Author and Year

Measuring Method (Clin, Histo, Radiogr)

Study Type (CCT, RCT, etc.)

32 (16 with BG covered with calcium sulfide/ 16)

16 (44.0 1 15.9; NA)

40 (NA; 26–69)

40 (20 with corticocancellous porcine bone + collagen membrane/20)

20 (10 with AB + titanium membrane/10 titanium membrane only)

80 (T1: 21 with 1.50 mg/ml rhBMP-2 + ACS; T2: 22 with 0.75 mg/ml rhBMP-2 + ACS; T3: 17 with ACS only/C: 20)

39 (26 with PG/PL sponge/13)

Full-thickness flap/yes/ amoxicillin (4x2g/d) and 4d CHX (0.12%) and Nimesulide (3x200mg/d)

Partial thickness flap (full-thickness flap on reentry)/no/ amoxicillin (10 × 1.5g/d) and 15d CHX (0.12%)

Full-thickness flap/yes/ penicillin or cephalosporin (7–10d) and 14d CHX (0.12%) and analgesics as needed

Full-thickness flap/no/ 14d CHX (0.2%) and analgesics as needed

Full-thickness flap/no/ doxycycline (7 × 200mg/d) and naproxen (7x750mg/d) and 14d CHX (0.12%) and analgesics as needed

Full-thickness flap/no/ penicillin (7 × 1,5 g/d) and 15d CHX (0.12%) and analgesics as needed

Full-thickness flap/yes/ penicillin (7 × 1g/d) and 14d CHX (0.12%) and analgesics as needed

Full-thickness flap/yes/ penicillin (7 × 1g/d) and CHX (0.2%) and analgesics as needed

Surgical Variety: Flap/Primary Closure/ Pharmacological Treatment

0/None

0/Membrane exposure in 5 subjects

0/Oral edema (75%), mouth pain (68%), and oral erythema (46%)

9/Dropouts unrelated to treatment

0/None

0/None

0/None

3/Membranes exposed after 3 months

No. of Dropouts/ Complications

7–9

6

4

6

4–6

6

6

6

Follow-Up (Months)

1.T: −0.7 1 1.4 C: −3.6 1 1.5 2.T: −0.2 1 0.8 C: −0.4 1 1.2 3.T: −0.4 1 0.8 C: −0.5 1 1.0 4. NA

1. NA 2. NA 3. NA 4. T: 8.40 1 3.35 C: 8.80 1 2.93

1. T: −1.40 1 1.97 C: −1.40 1 0.98 2. NA

1. T: −2.5 1 1.2 C: −4.5 1 0.8 2. N/R

1. T1: −0.02 1 1.2 T2: −0.62 1 1.39 T3: −1.00 1 1.40 C: −1.17 1 1.23 2. NA 3. NA 4. NA

1. T: +1.3 1 1.9 C: −0.8 1 1.6 2. T: −0.2 1 1.0 C: −0.6 1 1.0 3. T: −0.1 1 1.1 C: −0.8 1 1.5 4. NA

1. T:+1.3 1 2.0 C:-0.9 1 1.6 2. T:-0.1 1 0.7 C:-1.0 1 0.8 3. T: −0.1 1 0.7, C: −0.8 1 0.8 4. NA

1. T: −0.38 1 3.18 C: −1.00 1 2.25 2. NA 3. NA 4. T: −6.43 1 2.78 C: − 4.00 1 2.33

1. T: −0.38 1 0.22, C: −1.50 1 0.26 2. NA 3. NA 4. T: −5.81 1 0.29 C: −3.94 1 0.35

1. T: −0.28 1 0.18 C: −1.0 1 0.0 2. NA 3. NA 4. T: −5.43 1 1.1 C: −2.92 1 1.61

MVAR Dimension Changes (in mm) 1. Mid-buccal 2. Mesial 3. Distal 4. Socket Fill

1.T1: +3.27 1 2.53 T2: +1.76 1 1.67 T3: +0.82 1 1.40 C: +0.57 1 2.56 2. NA

NA

1. T: −1.2 1 0.9 C: −2.6 1 2.3 2. N/R

1. T: −3.48 1 2.68 C: −3.06 1 2.41 2. N/R

1. T: −1.31 1 0.24 C: −4.56 1 0.33 2. NA

1. T: −1.71 1 0.75 C: −4.43 1 0.72 2. NA

MHAR Dimension Changes (in mm) 1. Whole Ridge 2. Buccal Plate

All implants could be placed in both groups/GBR was needed in some sockets of the test group/NA

NA

All implants could be placed/no augmentation needed in: T1: 18/21 (86%) T2: 12/22 (55%) T3: 10/17 (59%) C: 9/20 (45%)/NA

All implants could be placed (with good primary stability)/NA/NA

All implants could be placed/ some sites required additional osseous graft and membrane/after 2 months, no implant was lost

No implants inserted

No implants inserted

No implants inserted

Insertion of Implant Possible/ Simultaneous Augmentation Needed/Implant Survival

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10 (46.3; 35–60)

80 (47.4; NA)

45 (NA; 35–64)

24 (12 with tetracycline-hydrated FDBA + collagen membrane/12)

32 (16 with PG-; PL-membrane/16)

16 (52.6 1 11.8; NA)

24 (51.5 1 13.6; 28–76)

20 (10 with e-PTFE membrane/10)

No. of Sockets (Test Group +BSM/Control Group)

10 (49.5; NA)

No. of Patients (Mean Age; Range of Age) (in Years)

TABLE 2 Summary of Studies on Arp that Determine Alveolar Ridge Dimension Changes

6 Alveolar Ridge Preservation 1253

Max anteriors/only sockets without severe bone loss

Max and mand anteriors and premolars/four-wall defects with intact buccal plate between 1–3 mm thickness

Max and mand premolars and molars

Max and mand premolars/ presence of buccal and oral wall + residual periodontal attachment of at least 6 mm

Max and mand anteriors and premolars/more than 50% of the buccal bone height present

Max and mand anteriors and premolars/only defects with intact buccal bone plate

Max anteriors, premolars and molars and mand premolars and molars/ more than 50% of the buccal bone height present

Clin. + Histo

Radiogr. + Histo

Clin.

Clin. + Radiogr. + Histo

Clin. + Radiogr.

Cin.

Clin. + Radiogr.

RCT

RCT

RCT

RCT

RCT

RCT

RCT

Pelegrine and colleagues 201014

Brownfield and colleagues 201217

Barone and colleagues 201340

Hauser and colleagues 201327

Jung and colleagues 201319

Thalmair and colleagues 201320

Kotsakis and colleagues 201421

26 (42.3; 21–68)

30 (46.2; 24–72)

40 (NA; 48 [in C]-65 [in T1])

23 (47; 22–75)

58 (40.5; 29–62)

17 (NA; 25–69)

13 (47.5 1 10.3; 28–70)

40 (51.27 1 8.4; 36–68)

30 (T1: 12 with ABBM + CM; T2: 12 with CPS + CM/C: 6)

30 (T1: 8 with xenograft (corticocancellous porcine bone) and AGG; T2: 8 with AGG only; T3: 7 with xenograft only/C: 7)

40 (T1:10 with β-TCP; T2:10 with DBBM-C/CM; T3:10 with DBBM-C/SPG /C: 10)

23 (T1: 9 with PRF; T2: 6 with PRF + Flap/C: 8)

58 (29 with corticocancellous porcine bone + collagen membrane/29)

20 (10 with DBA paste/ 10)

30 (15 with AB marrow graft/15)

40 (22 with MGCSH/ 18)

Flap free/no/amoxicillin (7 × 1.5g/d) and CHX-gel (0.2%) and ibuprofen (3 × 1.6g/d)

Flapfree/no/ibuprofen (600 mg) and 14d CHX (0.2%)

Flapfree/No/5d mefenacid (analgesic), amoxicillin and CHX (0.2%)

Flap free (except T2 with full flaps)/NA/ paracetamol

NA/no/nimesulide 100 mg (analgetic)

No flap/no/amoxicillin (7 × 1.5g/d) OR clindamycin (7 × 0.6g/d) and 14d CHX (0.12%) and analgesics as needed

Full-thickness flap/yes/ na

Flap free/no/amoxicillin (5 × 2g/d) and nimesulide (5 × 200mg/d) and 14d CHX (0.12%)

2/Reasons unrelated to the treatment

0/None

0/None

0/2 Bone biopsies (1 × T2/1 × C) broke during withdrawal

0/None

0/1 Dropout for histol. assessment due to complications on reentry

0/None

0/None

5

4

6

2

4

2 1⁄2–3

6

3

1. NA 2. NA 3. NA 4. NA

1. T1: −0.79 1 0.5 T2: −0.85 1 0.6 T3: −1.45 1 0.7 C: −2.29 1 1.1 2. NA

1. T1: −1.39 T2: −1.26 C: −2.53 2. NA

1. T1: −2.0 1 2.4 T2: 0.0 1 1.2 T3: 1.2 1 2.9 C: −0.5 1 0.9 2. NA 3. NA 4. NA

1. T1: −6.1 1 2.5 T2: −1.2 1 0.8 T3: −1.4 1 1.0 C: −3.3 1 2.0 2. NA

1. NA 2. T1: −1.21 1 0.40 T2: −0.86 1 0.34 C: −0.77 1 0.17 3. T1: −0.76 1 0.25 T2: −2.15 1 1.05 C: −2.07 1 0.81 4. NA

1.C: −2.1 1 0.6 T: −1.1 1 0.96 2.C: −1.0 1 0.7 T: −0.3 1 0.76 3. C: −1.0 1 0.8 T: −0.3 1 0.85 4. NA

1. C: −3.6 1 0.72 T: −1.6 1 0.55 2. NA

1. T1: −0.06 T2: −0.42 C: −0.43 2. NA

1. T:0.8 1 1.2 C:1.2 1 0.4 2. NA 3. NA 4. NA

1. T: −0.62 1 0.51 C: −1.17 1 0.26 2. NA 3. NA 4. T: −10.06 1 1.1 C: −10.44 1 0.84

1. T: −0.5 1 1.1 C: −1.2 1 0.6 2. T: −0.2 1 0.6 C: −0.5 1 0.9 3. T: −0.4 1 0.9 C: −0.5 1 1.1 4. T: 11.3 1 2.8 C: 10.0 1 2.3

1. T: 1.0 1 0.4 C: 1.3 1 1.0 2. T: 0.8 1 1.0 C: 0.9 1 0.9

1. T: −1.14 1 0.87 C: −2.46 1 0.4 2. T: −0.9 1 0.81 C: −1.83 1 0.77

1. T: 2.0 1 1.1 C: 3.2 1 1.8 2.NA

8 implants in T1, 9 implants in T2, and 3 implants in C/2 of 3 patients in C required additional Augmentation/after 12–20 months Implant survival was 94.1% (1 lost in T1)

NA

NA

All implants could be placed with good primary stability (except for 1 in T2)/No/NA

All implants could be placed/C: 46.4% T: 7.1% /NA.

All implants could be placed/ NA/NA

20 implants were placed/5 control sites needed additional augmentation/NA

NA

Clinical Implant Dentistry and Related Research, Volume 18, Number 6, 2016

Calculated values. NA = data not available; MHAR = mean horizontal alveolar ridge, MVAR = mean vertical alveolar ridge; RCT = randomised controlled clinical trial; CCT = controlled clinical trial; BSM = Bone substitute material; ePTFE = expanded ploytetrafluorethylen; PG/PL = polyglycolide/ polylactide; BG = bioactive glass; DFDBA = demineralized freeze-dried bone allograft; FDBA = mineralized freeze-dried bone allograft; MGCSH = Medical grade calcium sulfate hemihydrate; rhBMP-2 = recombinant human Bone Morphogenetic Protein-2; ACS = absorbable collagen sponge; AB = Autologous Bone; DBA = demineralized bone allograft; MGe-HA = Magnesium enriched; PRF = platelet-rich fibrin; β-TCP = b-tricalcium-phosphate; DBBM-C = deproteinized bovine bone mineral with 10% collagen; CM = collagen matrix; SPG = autogenous soft tissue punch graft; AGG = autogenous gingival graft; ABBM = Anorganic bovine bone mineral; CPS = Calcium phosphosilicate; Clin = Clinical; Histo = Histological; Radiogr = Radiographical; Max = Maxillary; Mand = mandibular.

Max anteriors/only one bone wall could be missing

Clin. + Histo

RCT

Aimetti and colleagues 200925

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Alveolar Ridge Preservation 7

Yes (examiner)

Yes (examiner)

NA

Yes (patient, examiner of CT scan)

NA

Yes (histological examiner)

NA

Yes (double blinded: histological Examiner + NA)

NA

Yes (radiogr. examiner, histo. examiner)

Yes (examiner)

NA

Yes (1 of 2 examiners)

NA

Yes (sealed envelopes)

Yes (flipping a coin)

NA

Yes

Yes

Yes (computerized)

Yes (alternative assignment)

Yes

Yes

Yes (flipping a coin)

Yes (computerized list)

Yes (picking numbers out of a hat)

Yes (computerized list and sealed envelopes)

Yes (computerized list and sealed envelopes)

Yes

Froum and colleagues 200215

Iasella and colleagues 200316

Serino and colleagues 200323

Fiorellini and colleagues 200526

Pinho and colleagues 200613

Barone and colleagues 200818

Serino and colleagues 200824

Aimetti and colleagues 201125

Pelegrine and colleagues 201014

Brownfield and colleagues 201217

Barone and colleagues 201340

Hauser and colleagues 201327

Jung and colleagues 201319

Thalmair and colleagues 201320

Kotsakis and colleagues 201421

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Identical Treatment Except for Intervention

1. Yes 2. Yes

1. Yes 2. Yes

1. Yes 2. Yes

1. Yes 2. Yes

1.Yes 2.Yes

1. Yes 2. Yes

1. Yes 2. Yes

1. Yes 2. Yes

1. Yes 2. No

1. Yes 2. Yes

1. Yes 2. No

1. No 2. No

1. Yes 2. No

1. Yes 2. Yes

1. Yes 2. Yes

1. Yes 2. Yes

1. Yes 2. Yes

1. No 2. No

Defined criteria for 1. Inclusion 2. Exclusion

30 (T1:12; T2: 12/C:6)

30 (T1: 8; T2: 8; T3: 7/C: 7)

40 (T1:10; T2:10; T3:10/C: 10)

23 (T1:9; T2:6/C:8)

58 (29/29)

20 (10/10)

30 (15/15)

40 (22/18)

20 (10/10)

40 (20/20)

20 (10/10)

80(T1: 21; T2: 22; T3: 17/C: 20)

39 (26/13)

24 (12/12)

30 (T1:10; T2:10/C:10)

32 (16/16)

32 (16/16)

20 (10/10)

Appropriate No. of Sockets (Test/Control)

26/2 (Out of disease)

30/0

40/0

23/0

58/0

20/0 For histo: 19/1 (due to complications on reentry)

13/0

40/0

16/4 (Reasons unrelated to therapy)

40/0

10/0

80/0

36/9 (Reasons unrelated to therapy)

24/0

19/0

16/0

16/0

7/3 (Due to membrane exposure)

Follow-Ups Completed/Dropouts (in patients)/Reason for Dropout (Yes/No)

No conflict of interest was claimed

No conflict of interest was claimed

No conflict of interest was claimed

No conflict of interest was claimed

NA

No conflict of interest was claimed

NA

NA

NA

No conflict of interest was claimed

No financial interest claimed

NA

NA

NA

NA

NA

NA

NA

Conflict of Interest Was Stated

Supported by a grant of from the National Center for Research Resources; a grant of the National Center for Advancing Translational Sciences of the National Institutes of Health (governmental institutions), and materials used were partially sponsored by Novabone Products LLC (industry)

Partially supported by Tecnoss (industry)

Supported by the University of Zurich (governmental) and partly by research grants of Geistlich Pharma and Degradable Solutions AG (industry)

NA

NA

Bone graft provided by Keystone Dental (industry)

NA

NA

Supported by the National Research Council, by the Ministry of Education, University and Research, by the Research Association for Dentistry and Dermatology (governmental institutions, Italy)

NA

Membranes provided by Dentsply, Friadent (industry)

Supported by a grant from Wyeth/Genetics Institute (industry)

NA

NA

Supported by a grant from Orthovita (industry)

Lifecore provided calcium sulfate (industry)

NA

NA

Source of Funding

High

Moderate

Moderate

Moderate

Low

Low

High

Low

High

Low

High

Moderate

High

Low

Moderate

High

Moderate

High

Risk of Bias

Clinical Implant Dentistry and Related Research, Volume *, Number *, 2015 Alveolar Ridge Preservation

NA = data not available.

NA

No

Camargo and colleagues 200022

Yes (radiogr. examiner)

Yes (examiner and statistic)

Yes (flipping a coin)

Lekovic and colleagues 199829

NA

Blinding

No

Randomization

Lekovic and colleagues 199728

Author and Year

Appropriate and Clearly Focused Question of the Study

TABLE 3 Quality Criteria of the Included Articles

8 1255

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Alveolar Ridge Preservation

9

Figure 2 Risk of bias.

outcome were available, but these showed contrary effects in MHAR, MVAR changes, and the amount of vital bone, which left us with inconclusive data for this group.

decrease than in the sockets treated with BSM, were noticeable and ranged from −3.3 1 2.0 up to −2.53 mm. The materials used consisted mainly of bioactive glass,22 polyglycolide/polylactide sponges,23,24 and various kinds of calcium sulfates or phosphates.19,21,25

BSM-Xenograft. Five studies examined the effect of xenografts on ARP in 168 sockets (96 test/71 control). All xenografts were used in combination with GBR techniques. Namely, the xenografts were corticocancellous porcine bone,18,20,40 DBBM-C,19 and anorganic bovine bone mineral.21 All studies showed a significantly lower decrease in all values for the BSM group. MHAR was given in all studies, varying from −2.5 1 1.2 to 0.79 1 0.5 mm in test groups and from −4.5 1 0.8 to −2.29 1 1.10 mm in control groups. The apico-coronal dimension is evaluated in three studies and even increased in one of them up to 1.2 1 2.9 mm in the BSM group. Anyways, the histological outcome was only given in one study and showed an increase in BSM 35.5 1 10.4% compared with unassisted healing 25.7 1 9.5% with a significance of p = .05.

GBR. The articles in this group, of which one was a CCT, either analyzed GBR alone28,29 or in combination with all kinds of BSM. Overall, nine articles were included, assessing 257 sockets (147 test/110 control). All of the articles reported values for MHAR changes, and eight of them showed significantly less reduction in the test groups, between −2.5 1 1.2 and −0.79 1 0.5 mm, than in the control groups −4.5 1 0.8 to −1.40 1 0.98 mm. Midbuccal MVAR changes were just given in six trials and ranged from −1.1 1 0.96 to 1.3 1 2.0 mm in the test group and between −3.6 1 1.5 and −0.5 1 0.9 mm in the control group. Also, bigger amounts of vital bone were measured in the test groups (up to 35.5 1 10.4%), giving positive results for GBR throughout all primary outcomes.

BSM-Alloplastic. Alloplastic materials were used for treatment by seven authors. They presented good evidence for an increase in vital bone and height (except Aimetti and colleagues25), while bone loss in the horizontal dimension occurred more than in the control groups except for the study of Jung and colleagues.19 Overall, 93 sockets in test groups were included in two CCTs and five RCTs, describing MHAR changes ranging from −6.1 1 2.5 to −1.26 mm, MVAR changes from −2.0 1 2.4 to 1.3 1 1.9 mm, and a percentage of vital bone ranging from 66.7% to 59.2%. The 72 control sockets, especially the MHAR changes that showed less

Bioactive Material. Only two articles gave information on ARP utilizing bioactive materials such as rhBMP-2 in different concentrations26 and PRF.27 In this group, only clinical and radiographical measurements were taken on 103 sockets, of which only 28 were left to heal unassisted. Midbuccal vertical measurements were only taken in the article of Fiorellini and colleagues26 and showed significantly less reduction in test groups, between −1.0 1 1.4 mm and −0.02 1 1.20 mm, than in the control −1.17 1 1.23 mm (p = .029). Also, for MHAR, this double-blinded placebo trial showed bigger improvements in the group of rhBMP-2 ranging from

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Clinical Implant Dentistry and Related Research, Volume *, Number *, 2015

0.82 1 1.40 to 3.27 1 2.53 mm, whereas the control group showed a growth in horizontal ridge dimension of 0.57 1 2.56 mm with a significance of p = .001. Both horizontal as vertical dimensions showed enhancement with the increasing amount of rhBMP-2 used. The second study reported similar results for bucco-oral dimension changes. No suitable parameters for the histological bone quality were found.

Secondary Outcomes Clinical/Radiographical Measurements. The buccal plate thickness was metered in two studies, of which one was restricted to a buccal plat thickness between 1 and 3 mm.17 They used AB marrow graft14 and DBA paste17 on 50 (25 test/25 control) sockets. The autograft trial showed less reduction in the test sockets. Similar to that, the allograft group even showed a gain of buccal bone. Furthermore, not only the buccal plate was assessed as a secondary outcome, but also, more measurements for apico-coronal dimension changes were taken on mesial and distal points, in five RCTs and one CCT. One hundred thirty-four sockets were treated with three xenografts,16,18,40 two alloplastics,23,25 and 1 bioactive material,27 while 100 sockets were left to heal unassisted. The data homogeneously delivered evidence that mesial and distal bone loss could be prevented by ARP, ranging from −0.3 1 0. 76 to −0.1 1 0.7 mm on mesial reference points and from −0.4 1 0.9 to −0.1 1 0.7 mm distal. Compared with the control groups, the mesial ridge decreased by −1.0 1 0.8 to −0.4 1 1.2 mm and the distal ridge decreased from −1.0 1 0.8 up to −0.5 1 1.0 mm. An exception of this trend was seen in Hauser and colleagues,27 where with PRF alone, less reduction or even increase was shown. Although in combination with a flap procedure, the better results were achieved by healing without treatment. The last dimensional parameter that was compared was the socket fill. It was assessed in six studies (two CCTs, four RCTs) of 174 sockets evenly distributed between groups. The socket fill measurements varied a lot between −10.06 1 1.1 and 11.3 1 2.8 mm and therefore did not seem to be very reliable. Anyways, two authors reported on more increase/less decrease in test groups, and four authors reported on more increase/less decrease in control groups, which seem to be a rather heterogeneous outcome.

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Histological Measurements (Table 4). The percentage of connective tissue that had invaded the former space of the root, instead of bone, was examined in two articles and accounted between 35.3% and 51.6% in the test groups, which was significantly less than in the control groups with 59.1 1 10.4 – 67.0%. The articles showed these effects in bioactive glass and DFDBA (30 sockets)15 and in corticocancellous porcine bone (40 sockets).18 More studies evaluated the amounts of residual bone graft left over after the healing period. It could only be done in the BSM group. Therefore, no comparison is available, and values ranged from 0–37 1 18%. The articles about the percentage of residual BSM contained 127 sockets filled with two allografts,15,16 two alloplastics,15,23,24 and one xenograft.18 Implant Placement and Survival. Four out of the 17 articles did not report anything about implant placement at all.13,19,20,25 In two CCTs22,28 and one RCT,29 implant placement was not even intended. The remaining 10 studies gave results on the necessity of additional augmentation, which in most cases was not needed. Two studies only noted that some sites in test18 or both groups16 underwent additional augmentation. The rest of the articles counted a total of 23 out of 231 (=9.9%) sites in the test groups and 31 out of 149 (=20,8%) sites in the control groups that were in need of further augmentation. Notably, all of the implant sites (except for three), which needed to be augmented in the test groups, were reported by one author using bioactive material for ARP.26 Further on, the author also reported on 50% of the additional augmentations in the control group. However, the implant survival was only stated in two trials. Iasella and colleagues16 reported that after 2 months, no implants were lost, while Kotsakis and colleagues21 showed an implant survival of 94.1% (one lost in a test group) after 12 to 20 months. Synthesis of the Meta-Analysis MHAR. The differences in mean horizontal ridge changes between the test and control groups are shown in the forest plot in Figure 3. Both the meta-analysis with (a) and without the multiarmed trials (c) significantly (p < .001) showed that the sockets in ARP groups were (a) 1.33 mm (95% CI: 0.69 mm; 1.97 mm) and (c) 1.42 mm (95% CI: 0.62 mm; 2.22 mm) wider than in the control groups. These results had been produced with an estimated variance between studies (tau

RCT

RCT

RCT

RCT

Iasella and colleagues 200316

Barone and colleagues 200818

Serino and colleagues 200824

Pelegrine and colleagues 201014

Max anteriors/only sockets without severe bone loss

Clin. + Histo

Max and mand anteriors and premolars/only four-wall defects

Clin. + Histo

Max and mand anteriors and premolars/“at least 8 mm residual alveolar bone height”

Max anteriors and premolars + mand premolars/NA

Clin. + Histo

Histo

Any/four-wall defect with 22 mm buccal plate bone loss

Defect location/ Defect Type

Histo

Measuring Method (Clin; Histo; Radiogr.)

24 (12 with tetracycline hydrated FDBA + collagen membrane/10)

24 (51.5 1 13.6; 28–76)

20 (10 with PG/PL sponge/10) after dropout: 16 (7/9)

30 (15 with AB marrow graft/15)

20 (NA; 32–64)

13 (47.5 1 10.3/28–70)

40 (20 with corticocancellous porcine bone + collagen membrane/20)

30 (T1:10 with BG; T2:10 with DFDBA/ C:10)

19 (54.9 1 11.9; 35–77)

40 (NA; 26–69)

No. of Sockets (Test Group +BSM/Control Group)

No. of Patients (Mean Age; Range of Age) [in Years]

Full-thickness flap/yes/ NA

Full-thickness flap/no/ 14d CHX (0.2%) and analgesics as needed

Full-thickness flap/yes/ amoxicillin (4 × 2g/d) and 4d CHX (0.12%) and nimesulide (3 × 200mg/d)

Full-thickness flap/no/ doxycycline (7 × 200mg/d) and naproxen (7 × 750mg/d) and 14d CHX (0.12%) and analgesics as needed

Full-thickness flap/yes/ doxycycline (13 × 0.1 mg/d) and 30d CHX (0.12%)

Surgical Variety: Flap/Primary Closure/ Pharmacological Treatment

0/None

4/Dropout reasons unrelated to therapy

0/None

0/None

0/None

No. of Dropouts/ Complications

6

3

7–9

4–6

6–8

Follow-Up (Months)

Mineralized bone: T: 45.47 1 7.21 C: 42.87 1 11.33

Mineralized bone: T: 59.2 1 22.4 C: 48.8 1 14.4

NA

NA

0

T: 36.6 1 12.6 C: 59.1 1 10.4

NA

29.2 1 10.1

NA

1. 28 1 14 2. 54 1 12

Total bone: T: 35.5 1 10.4 C: 25.7 1 9.5

37 1 18 (Stated as none vital bone)

1. T1: 35.3 T2: 51.6 2. C: 67.0

T1: 5.5 T2: 13.5

% Residual BSM

1. T1: 59.5 T2: 34.7 2. C: 32.4

% Vital Bone 1. Test 2. Control

% Connective Tissue 1.Test 2 Control

20 implants were placed/5 control sites needed additional augmentation/NA

All implants could be placed (with good primary stability)/ NA/NA

All implants could be placed in both groups/GBR was needed in some sockets of the test group/NA

All implants could be placed/some sites required additional osseous graft and membrane/after 2 months, no implant was lost

“An implant of appropriate size was placed in the healed sockets”/NA/NA

Insertion of Implant Possible/ Simultaneous Augmentation Needed/Implant Survival

Clinical Implant Dentistry and Related Research, Volume 18, Number 6, 2016

Calculated values. NA = Data not available; RCT = randomised controlled clinical trial; CCT = controlled clinical trial; BSM = Bone substitute material; ePTFE = expanded ploytetrafluorethylen; PG/PL = polyglycolide/polylactide; BG = bioactive glass; DFDBA = demineralized freeze-dried bone allograft; FDBA = mineralized freeze-dried bone allograft; MGCSH = Medical grade calcium sulfate hemihydrate; rhBMP-2 = recombinant human Bone Morphogenetic Protein-2; ACS = absorbable collagen sponge; AB = Autologous Bone; DBA = demineralized bone allograft; MGe-HA = Magnesium enriched; PRF = platelet-rich fibrin; β-TCP = b-tricalcium-phosphate; DBBM-C = deproteinized bovine bone mineral with 10% collagen; CM = collagen matrix; SPG = autogenous soft tissue punch graft; AGG = autogenous gingival graft; ABBM = Anorganic bovine bone mineral; CPS = Calcium phosphosilicate; Clin = Clinical; Histo = Histological; Radiogr = Radiographical; Max = Maxillary; Mand = mandibular.

RCT

Froum and colleagues 200215

Study

Study Type (CCT, RCT, etc.)

TABLE 4 Summary of Studies on Arp that Determine Histomorphology

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Alveolar Ridge Preservation

Figure 3 MHAR-forest: (A) all, (B) all 6 1 1 months, (C) without multi-armed trial, and (d) without multi-armed trial 6 1 1 months.

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squared) of (a) τ2 = 1.424 and (c) τ2 = 1.437. Further, it should be mentioned that (a) included 266 test and 193 control sockets, and (c) only included 160 test and 156 control sockets. Also, when focusing on only one point of time (6 1 1 months), similar results are shown, and the ridges are from (b) 1.31 mm (95% CI: 0.30 mm; 2.31 mm) to (d) 1.54 mm (95% CI: 0.44 mm; 2.64 mm) wider in test groups than in control groups. MVAR. The same meta-analysis was performed for the articles reporting on the vertical ridge dimension changes at a midbuccal reference point (Figure 4). There were (a) 266 experimental and 189 control sockets and (c) 206 test and 169 control sockets included. The test groups showed (a) 0.91 mm (95% CI: 0.55 mm; 1.27 mm) and (c) 1.08 mm (95% CI: 0.65 mm; 1.51 mm) more apico-coronal dimension after follow-up than the controls did. The degree of heterogeneity between groups, which was given by tau squared, amounted to (a) τ2 = 0.2761 and (c) τ2 = 0.2793. On the 6 1 1-month follow-up, even more promising results could be presented with a difference in ridge height of (b) 0.95 mm (95% CI: 0.46 mm; 1.44 mm) up to (d) 1.12 mm (95% CI: 0.62 mm; 1.63 mm) in the ARP group. Estimated variance between studies (tau squared) for these meta-analysis were between (b) τ2 = 0.2232 and (d) τ2 = 0.1747. Histo. Histological findings were limited to only (a) six studies including 74 experimental and 64 control sockets, and (c) four studies with an equal number of 54 sockets in each group as seen in Table 4. The meta-analysis (Figure 5) showed a mean difference of 3.66% (95% CI: −8.74%; 16.06%) in test groups with a heterogeneity across groups of τ2 = 196.3. Leaving out Froum and colleagues15 in (c) revealed slightly different results in the second meta-analysis. The mean difference amongst test and control groups accounted −1.07% (95% CI: −16.03%; 13.89%) less vital bone in the histological cores using ARP than in the ones that healed unassisted. The tau squared value for this finding in (c) was τ2 = 200.5. The level of heterogeneity was even bigger (τ2 = 346.1) for all the studies with follow-ups of 6 1 1 months (b). The amount of vital bone in test groups of this analysis accounted 0.86% (95% CI: −18.50%; 20.22%) more than in the control groups. These results are just in between the ones of (a) and (c).

Alveolar Ridge Preservation

13

DISCUSSION The present review was written with the goal to achieve as much data about different techniques of ARP as possible. Therefore, different histological and dimensional values were introduced as the outcomes. Both was needed to give evidence for the procedure because neither the bone quality (measured histological) nor the quantity and pure outer dimension of the ridge after extraction bring enough evidence on their own to legitimate ARP. Additionally, the success rate, in the means of feasibility and survival of the implant, was included as an outcome. Subsequently, the quality of the included articles was assessed in detail. This quality assessment showed a medium quality of the included literature. This should be kept in mind when looking at the results of this review. Primary Outcomes In order to review the effects of ARP, the following questions were asked: How much does socket preservation help in the means of dimensional changes and histological bone quality? What are the actual effects of ARP? And which is the most effective BSM/technique for this procedure? It was tried to answer these last questions in the narrative approach below, while the actual numerical results are presented in the meta-analytical part. Autografts and Xenografts. Both showed superior results in the test groups for all primary outcomes throughout all studies. However, only two articles on autografts and four on xenografts evaluated these materials, and proximately, the power of these conclusions is to be looked up on very carefully. Still, both kinds of BSM seem to be suitable for ARP, as it had been shown by other authors.41–43 Allografts: Three articles evaluated allografts and revealed heterogeneous data. For each value, MHAR change, MVAR change, and % of vital bone, only two articles were available. The one article showed better results for experimental groups, and in the other one, better results for control groups were reached. Hence, information on allogen materials up to now seems to be inconclusive, even though in the further literature, El-Chaar44 presented results, in which allografts successfully maintained ridge dimension and enabled implant placement. Alloplastics. The most studies in this review described alloplastic materials. For this group, there seemed to be

14

Clinical Implant Dentistry and Related Research, Volume *, Number *, 2015

Alveolar Ridge Preservation

Figure 4 MVAR-forest: (A) all, (B) all 6 1 1 months, (C) without multi-armed trial, and (D) without multi-armed trial 6 1 1 months.

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15

Figure 5 Histo-forest (A) all, (B) all 6 1 1 months, and (C) without multi-armed trials.

benefits in the apico-coronal height in test groups, while the decrease in vertical dimension seemed to be less in control groups. Also, the percentage of vital bone resulted in higher values in the test groups. This leaves us to believe that alloplastic materials only seem to be best in use when it is intended to prevent vertical and not horizontal shrinkage.

the experimental sites, between −1.71 1 0.75 and −1.31 1 0.24 mm in width and between −0.38 1 0.22 and −0.28 1 0.18 mm in height, which shows that GBR can be accounted as a dependable technique, additional to bone grafting or alone, to preserve alveolar ridges. This finding concludes with previous clinical trials on GBR.46,47

GBR. The concept of GBR is based on the idea that a barrier can stop epithelial cells of the mucosa to migrate into the socket and interfere with the wound healing.45 It has been evaluated by nine trials in this review. And while all of the studies brought evidence that dimensional bone loss was less in test groups compared with unassisted socket healing and new bone formation was bigger, only one study13 showed no intergroup differences in horizontal changes. Since most of the articles on GBR additionally used BSM, it is interesting to take a look at the trials that assessed GBR alone.28,29 Both trials measured less reduction for MHAR and MVAR in

Bioactive Material. By the use of bioactive material, it is tried to apply different mesenchymal cells that are supposed to proliferate and differentiate in the alveolus, which is assumed to improve healing. This has been shown to work in clinical and preclinical trials for rhBMP-248,49 and PRF.50 These are the materials used by the two articles26,27 included in this review. Both showed less reduction in bucco-oral ridge dimension, while only one study measured the ridge height, which was less reduced in the experimental group compared with the controls. Fiorellini and colleagues26 even showed an increase for ridge width. Unexpectedly, the control

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Clinical Implant Dentistry and Related Research, Volume *, Number *, 2015

group also showed an increase of bone width, which was only seen in one trial.17 This plus the insufficient amount of studies on bioactive materials in this review is limiting the following conclusion. Still, it seems like ARP could benefit in using bioactive materials. Secondary Outcomes Clinical/Radiographical Measurements. In addition, similar effects were observed throughout the secondary outcomes. Only two trials, one for an autograft14 and one for an allograft,17 made the suggestion that the resorption of the buccal bone plate could be prevented by socket preserving techniques. In on of them, the buccal plate thickness was limited to be at least 1 to 3 mm before intervention. Therefore, this cannot be considered as a general indication for the use of ARP, even though it had been proven to work earlier.51 On mesial and distal reference points, the effects shown across nine studies are similar to the ones on a midbuccal reference point, and reveal significantly less ridge reduction in test than in control groups. Anyways, this adds to the findings discussed and proves that ARP is superior to preserve vertical dimension, instead of unassisted socket healing. The socket fill, which was measured in six papers, varied a lot from −10.06 1 1.1 to 11.3 1 2.8 mm. Hence, no conclusion can be drawn from this outcome. The heterogeneity of these measurements could be explained by the shady definition of “socket fill” and the technical difficulties in measuring it. As a consequence, it should not be considered as an optimal variable to assess ARP. Histological Measurements. As far as histology is concerned, more connective tissue seemed to invade the empty sockets in control groups, than in the BSM groups, while this was only taken into measurement in two trials.15,17 Combined with the outcomes of vital bone percentage in the cores, where more vital bone was found in experimental sockets throughout all studies (except one16), this seems to prove the osseoinductive and osseoconductive effects of ARP. Further, it was attempted to measure the resorbability of the BSM in the last histological outcome. The percentage of residual BSM showed the best results of 0% for polyglycoid/polylactide sponges used in the articles of Serino and colleagues,23,24 while other articles reported on values between 13.5 and 37 1 18% for allo and xenografts. An exception of this was the finding of

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only 5.5% of residual bioactive glass in the trial of Froum and colleagues.15 Since 0% of residual bone seemed to be a very unlikely outcome, which only occurred in the articles of one author, and the rest of the trials gave very limited results, no conclusions could be drawn. However, all histological measurements should be considered with care because only very small trephine cores could be gained during reentry, and they might not be representative. Furthermore, it can make a big difference whether you observe more coronal or more apical sections of the biopsy, and healing times in the histological trials still varied between 3 and 9 months which is a lot concerning reconstruction and healing processes. Implant Placement and Survival. Lastly, the feasibility of implant placement without augmentation and the implant survival should be discussed, as they are important parameters to determine whether the ARP technique was successful or not.30 Additional augmentations were needed in 9.9% of the test sites and 20.8% of the control sites that reported on such modalities, which brings an advantage for ARP. These findings disclude with the DGI consensus statement from Weng and Schliephake,52 which presented 42% additional augmentations needed in the control group, whereas only 4% of the test sockets needed further augmentation. But since most of the cases that needed augmentation in this article were revealed in only one study,26 the findings of Weng and Schliephake might actually be closer to the true benefit of ARP than the ones presented in this review. Still, to finally asses this question, further investigation should be conducted. Also, implant survival was not reported well enough to bring any conclusions as only two trials stated the survival rate as an outcome, and one of them only evaluated it over a period of 2 months. Meta-Analysis Following the results of the meta-analysis, it can be assumed that about 1.33 mm (95% CI: 0.69 mm; 1.97 mm) up to 1.42 mm (95% CI: 0.62 mm;2.22 mm) of mean bucco-oral ridge width and about 0.91 mm (95% CI: 0.55 mm; 1.27 mm) to 1.08 mm (95% CI: 0.65 mm; 1.51 mm) of mean apico-coronal ridge height can be preserved by using ARP techniques, instead of letting the sockets heal unassisted, regardless of the period of follow-up.

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Looking only at the studies with a defined follow-up of 6 1 1 months gives us more comparable and probably even more true results, especially when considering that the bone remodeling mainly takes place in this period of time, as already stated in the Introduction. During this period, the preservation of ridge width can be assumed to be between 1.31 mm (95% CI: 0.30 mm; 2.31 mm) to 1.54 mm (95% CI: 0.44 mm; 2.64 mm), and in ridge height about 0.95 mm (95% CI: 0.46 mm; 1.44 mm) up to 1.12 mm (95% CI: 0.62 mm; 1.63 mm). Considering the heterogeneity in these findings, the MVAR dimension changes can be believed to be appropriate (τ = 0.418 in (d) and τ = 0.528 in (c)), while the results for MHAR changes should be regarded with care (τ = 1.33 and τ = 1.19). The amount of vital bone changes should be considered with even more attention as values for heterogeneity went up to τ = 14.0 to 18.6. Even different tendencies in the outcome occurred. The meta-analysis including the multiarmed trials revealed 3.66% (95% CI: −8.74%; 16.06%) more bone in test groups, while the one excluding multi-armed trials showed about −1.07% (95% CI: −16.03%; 13.89%) less vital bone in the experimental sockets. These heterogeneities mainly occur because of two studies: the multiarmed study of Froum and colleagues15 giving by far the highest differences for ARP groups and the study of Iasella and colleagues,16 which presents even less bone (up to −26%) in test sites. It also explains the difference in outcomes that are a direct result of the exclusion of Froum and colleagues.15 The same applies for the metaanalysis focusing only on the articles with a histological follow-up of 6 1 1 months, which still includes those two articles and shows a 0.86% (95% CI: −18.50%; 20.22%) higher percentage of vital bone in the test than in the control groups. Anyways, as there are so few well-reported articles on the histological effects of ARP, neither these studies could be excluded, nor can the results of this analysis be accounted as sufficient. Therefore, further research, especially on the quality of the preserved bone, should be considered.

Additional Factors Since periodontal healing as well as ARP is a complex issue, it does not just proceed as described in the boundaries of this review. There are many different factors affecting it. These factors also limited the results of the

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present article, and therefore, some of them should be immediately dealt with. Healing Time. The alveolar ridge volume continuously shrinks, while inside the socket, new bone is built and the bone quality continuously increases.53,54 In conclusion, the best timing for implant insertion can be described to be as fast as possible, but it still late enough to allow the bone to heal. The included articles could not present such a point in time because the follow-up was quite heterogeneous from 2.5 to 9 months. Smoking. Even though the mechanisms are not fully understood, it is long known that smoking is associated with delayed wound healing. Smoking has also been shown to be associated with about 0.5 mm of alveolar width decrease.5,55 Three of the reviewed studies included smokers,16,18,20 and only seven explicitly excluded smoking patients. Still, one of the articles, excluding smokers, used an exclusion criterion of less than 20 cigarettes per day.19 This did not seem appropriate. The rest did not report on smoking habits at all, and therefore, the limitation factors of smoking in this review are hard to assess. Antimicrobials. The opposite effects of smoking are achieved by the use of antimicrobials, which is a typical method in periodontal treatment. By rinsing with an antimicrobial-like chlorhexidine (CHX) for about 1 month after extraction, much of the dimensional loss can be eliminated.5,56 Of all articles in the present study, only two14,27 did not report on the use of CHX. However, the trials where a 4- to 30-day CHX rinse was introduced as postextraction care (except two articles23,24) additionally used antibiotics. These findings interfere in a positive way with the results of the review, but as the same postextraction therapy was given for both test and control group, the tendency of the outcomes should still be the same. Flap Management. In an earlier review, it had been stated that it would be crucial for ARP to perform either primary closure or no flap management at all.30 The given article drew their conclusion from the fact that in their review, all articles, which showed better results for the test groups in both MHAR and MVAR dimension, performed one of the abovementioned techniques. Since in this article all studies that fulfilled the previously

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described criteria performed primary closure (except for one16), it seems like this would be the best way to secure the healing process. Anyways, the methods that assessed this matter should be questioned. CONCLUSIONS 1. Resorption processes in the alveolar bone after extraction cannot be totally stopped by ARP, and unassisted sites confirmed that resorption is higher in horizontal than in vertical dimension. 2. Applying ARP compared with unassisted socket healing can preserve approximately 1.31 to 1.54-mm bucco-oral bone width and 0.91 to 1.12-mm bone height. 3. No conclusive evidence could be found through the meta-analysis for the advantage of ARP concerning the amount of vital bone. Therefore, further research needs to be accomplished. 4. No recommendation can be made referring to any of the ARP techniques. Still, the evidence on allografts stayed inconclusive and hence needs to be further assessed in well-documented trials in the future. Further on, GBR and bioactive materials showed the most promising results, while bioactive materials should still be further investigated due to the lack of high-quality evidence to finally evaluate them yet. 5. It seemed that less additional augmentations were needed at the time of implant insertions in ARP sites. In addition, more data should be collected in further research for this outcome to finally assess the patient benefit of ARP. 6. Furthermore, well-documented research is also needed on short healing periods (e.g., 3 months), histological aspects, limitation factors, and the long-term survival of implants in ARP sites. REFERENCES 1. Atwood DA. Some clinical factors related to rate of resorption of residual ridges. J Prosthet Dent 2001; 86:119–125. 2. Devlin H, Sloan P. Early bone healing events in the human extraction socket. Int J Oral Maxillofac Surg 2002; 31:641– 645. 3. Araujo MG, Lindhe J. Dimensional ridge alterations following tooth extraction. An experimental study in the dog. J Clin Periodontol 2005; 32:212–218.

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The Effects of Alveolar Ridge Preservation: A Meta-Analysis.

The aim of this article was to analyze the horizontal, vertical, and histological effects of alveolar ridge preservation (ARP) versus the ones of unas...
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