Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis

YIJOM-4305; No of Pages 14

Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx https://doi.org/10.1016/j.ijom.2019.10.007, available online at https://www.sciencedirect.com

Network Meta-Analysis Pre-Implant Surgery

Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis

J. V. d. S. Canellas1, F. G. Ritto1, C. M. d. S. Figueredo2, R. G. Fischer2, G. P. de Oliveira3, A. A. Thole3, P. J. D. Medeiros1 1

Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Rio de Janeiro State University, Rio de Janeiro, Brazil; 2 Department of Periodontology, Faculty of Dentistry, Rio de Janeiro State University, Rio de Janeiro, Brazil; 3Department of Histology and Embryology, Biology Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil

J. V. d. S. Canellas, F. G. Ritto, C. M. d. S. Figueredo, R. G. Fischer, G. P. de Oliveira, A. A. Thole, P. J. D. Medeiros: Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis. Int. J. Oral Maxillofac. Surg. 2019; xxx: xxx–xxx. ã 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Abstract. In this systematic review and network meta-analysis including only randomized clinical trials (RCTs), different grafting materials used in alveolar ridge preservation after tooth extraction were analysed, focusing on histomorphometric new bone formation (NBF) in core biopsies obtained during implant placement. The PubMed, Embase, Cochrane Library, Web of Science, Scopus, and LILACS databases, as well as the grey literature, were searched for published and unpublished trials (from database inception to January 14, 2019). The primary outcome was the percentage of NBF. The secondary outcomes were the percentage of residual biomaterial and the percentage of soft tissue. An arm-based network meta-analysis was performed. The rank of intervention efficacy was obtained to measure the probability of each biomaterial being ranked first across all interventions. A total of 1526 studies were found, of which 38 were included for quantitative analysis. Three trials were rated as having a high risk of bias and 35 trials as having an unclear risk of bias. The network meta-analysis showed that nine grafting materials decreased NBF and 25 did not decrease NBF. The grafting material with the highest amount of NBF was plasma rich in growth factors. Due to the lack of studies with a low risk of bias, further RCTs are needed for definitive conclusions.

0901-5027/000001+014

Key words: evidence-based dentistry; alveolar ridge preservation; grafting materials; network meta-analysis. Accepted for publication 9 October 2019

ã 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

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Canellas et al.

Animal and human studies have demonstrated that, after tooth extraction, the alveolar bone undergoes a physiological and inevitable remodelling process that results in variable bone resorption1–3. The bone reduction is probably correlated with disruption of the blood supply and the osteoclastic activity that occurs during alveolar healing4. This process could be an important limitation during subsequent implant rehabilitation. Grafting materials are widely used to prevent alveolar bone loss after tooth extraction. These can be grouped into various classes of bone substitute biomaterials (i.e., xenograft, allograft, alloplast, autologous, and platelet concentrate) with different physicochemical properties. However, there is debate and concern about their efficacy in the induction of new bone formation (NBF) and about the capacity of the residual graft particles to resorb, allowing new trabecular bone formation. Some of the most used biomaterials for alveolar ridge preservation are xenograft5–7, allograft8,9, alloplast10, and platelet concentrate11,12. However, two biomaterials belonging to the same class may provide different results in NBF13,14, which is probably due to differences in the manufacturing process14,15. The network meta-analysis has emerged as a new evidence synthesis tool. It is a statistical technique that allows the comparison of multiple treatments in the same analysis16. While the traditional metaanalysis seeks to combine evidence from studies comparing only two different options, the network meta-analysis allows the estimation of metrics for all possible comparisons simultaneously, even those not previously compared in primary studies, using direct and indirect evidence. This statistical approach ranks the intervention to determine the best option. Furthermore, it also reveals the second best, third best, and so forth17. With regard to biomaterials to preserve the alveolar bone after tooth extraction, several options are available. Some systematic reviews using a traditional pairwise meta-analysis have tried to integrate different grafting materials to determine the best choice to reduce bone loss18–20. Nevertheless, the network meta-analysis seems to be the most powerful method to aid in the evidence-based treatment decision when several options of intervention are available. One previous network metaanalysis evaluated the efficacy of different grafting materials for socket filling21. However, the authors only investigated linear changes. The objective of the present network meta-analysis was to analyse

histomorphometric NBF in core biopsies obtained during implant placement, and not bone volume or dimensions. This study is therefore novel in performing a network meta-analysis to determine the effect of different grafting materials on NBF using histomorphometric data. The purpose of this study was to synthesize information from randomized clinical trials (RCTs) to answer the following focused question: Which grafting material used for alveolar preservation after tooth extraction produces the highest amount of new bone formation, considering histomorphometric results? Materials and methods Search strategy and study protocol

A comprehensive electronic search in the MEDLINE/PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, and Latin American and Caribbean Health Sciences Literature (LILACS) databases, as well as the grey literature, was conducted. The search strategy used both medical subject headings terms (MeSH) and free-text words. The electronic database searches were supplemented with manual searches for published and unpublished trials. The PICOS framework strategy is provided in the Supplementary Material, to permit adequate reproduction of this study (Table S1). The protocol for this systematic review was registered in the PROSPERO database (CRD42019121926). The PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to ensure the high methodological quality of this review22. The search was limited to human studies, and the last electronic search was performed on January 14, 2019. The ClinicalTrials.gov registry platform (http:// www.clinicaltrials.gov) was screened to find studies in the grey literature. The reference lists of the trials identified were cross-checked. A manual search was performed in the following relevant journals: International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial Surgery, Journal of Clinical Periodontology, Journal of Dental Research, Clinical Oral Implant Research, and International Journal of Oral and Maxillofacial Implants. Subsequently, the articles were imported into Endnote X9 software (Thompson Reuters, Philadelphia, PA, USA) where duplicates were automatically removed. If a study was published more than once, only the report with the most informative and complete

data was included. No language restriction was applied in the search process. Selection criteria

The inclusion criteria were as follows: study performed on humans; study reporting histomorphometric results regarding alveolar preservation with different grafting materials; RCT; study that described in detail the method of biopsy harvesting and histological processing. Studies with inadequate follow-up, in vitro studies, studies not focused on histomorphometric analysis, and observational studies were excluded. At least two different grafting materials had to have been compared in the primary studies, and the placebo intervention was defined as natural healing without any socket filling. Data extraction

Titles and abstracts of the studies identified in the screening were independently evaluated by two reviewers (J.V.C. and F.G.R.), who screened the titles and selected the abstracts for full-text inclusion. The full-text articles were obtained for those studies that the authors considered relevant and for those where there was uncertainty regarding the selection criteria. The level of agreement between the review authors was calculated by kappa statistic; a kappa value of between 0.40 and 0.59 is considered fair agreement, between 0.60 and 0.74 is considered good agreement, and above 0.75 is considered excellent agreement. Disagreement regarding inclusion was resolved by discussion. The primary outcome was the percentage of NBF at least 3 months after tooth extraction. The secondary outcomes were the percentage of residual grafting material at least 3 months after tooth extraction and the percentage of soft tissue at least 3 months after tooth extraction. The risk of bias of the studies was assessed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions23. Three review authors (J.V.C., A.A.T., and G.P.O.) assessed the risk of bias independently. The reviewers were blinded to the information about the articles, such as the journal, authors, institution, and direction and magnitude of the results. Any disagreements between the authors were resolved by discussion. Statistical analysis

An arm-based network meta-analysis was accomplished to compare the effects of

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

Grafting materials in alveolar preservation multiple commercial and non-commercial biomaterials, including information about grafting materials that have not previously been compared directly. The network meta-analysis in an extension of the classical pairwise meta-analysis, and it can be used to compare many different treatments, going beyond focusing on pairwise comparisons. This technique allows the synthesis of large amounts of information, the estimation of the relative effectiveness, and the ranking of interventions according to outcomes. The traditional meta-analysis focuses on direct comparisons between two treatments in the included primary studies. However, many different grafting materials can be used for socket filling after tooth extraction, and it is not feasible to compare all interventions simultaneously by conducting a systematic review. The network meta-analysis makes this possible. For instance, if there is one study comparing intervention A versus B, and another study comparing B versus C, it is possible to compare A versus C through indirect evidence using network meta-analytical methods. In this case, B is a common comparator where the treatment comparisons A and C are anchored. The mean values for NBF (%), residual grafting material (%), and soft tissue (%), the standard deviations, and the numbers of patients randomized to each group were

collected from the selected studies. These data were synthesized to obtain the summary standardized mean difference, with 95% credible interval, network plot, and a comprehensive ranking of all treatments. The effect difference between two grafting materials can be estimated through confidence intervals (CI). If 0 was within the corresponding 95% CI, this meant that the two treatments did not differ significantly. When the 95% CI was entirely on the negative side, this biomaterial showed a statistically significant negative effect on bone density. In contrast, when the 95% CI was entirely on the positive side, this biomaterial showed a statistically significant positive effect on bone density. The study effect sizes were then synthesized using a random-effects network meta-analysis model. Only studies in which biopsy harvesting was performed between 3 and 6 months after tooth extraction were included in the quantitative synthesis. The estimated treatment rank probabilities were used to estimate the relative efficacy of all regimens in each iteration, and then to calculate the proportion of each intervention being ranked first across all interventions. All analyses were performed using the software R version 3.5.1 with the pcnetmeta package for Mac OS X computer system. This package is available from the Comprehensive R

3

Archive Network (CRAN) at https:// CRAN.R-project.org/ package=pcnetmeta.

Results

The PRISMA flow diagram of the screening and selection process is presented in Fig. 1. A total of 2537 studies were identified initially, and after the exclusion of duplicates, 1526 records remained. After the eligibility process, 1380 records were excluded and 146 full-text articles were obtained. After full-text reading of these studies, 38 RCTs fulfilled the inclusion criteria and were selected for qualitative analysis5–11,13,14,24–52. Finally, 33 studies were included for network metaanalysis5–11,13,14,24,26,28–35,37–44,46,48–52. The reasons for exclusion are listed in Fig. 1. The kappa value was 0.91, so agreement was considered to be excellent. None of the trials included in this review was assessed as having a low risk of bias for all of the domains. Thirty-five trials were assessed as having an unclear risk of bias, because each of these trials had an unclear risk of bias in one or more domains5–8,10,13,14,24–47,49–52. The remaining three trials were assessed as having a high overall risk of bias, because each of these trials had a high risk of bias in one or more domains (Fig. 2)9,11,48.

Fig. 1. PRISMA flow diagram of the screening and selection process.

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

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Canellas et al.

Fig. 2. Risk of bias summary: review authors’ judgements.

The characteristics of the selected studies are presented in the Supplementary Material (Table S2). A total of 1268 extractions in 985 patients were analysed. Finally, 34 biomaterials were compared using the histomorphometric data of 1146

bone biopsy specimens. A parallel-group design was utilized in 28 studies5–10,14,24– 30,33–35,37,39,40,43,44,46,48–52 , while 10 had a split-mouth design11,13,31,32,36,38,41,42,45,47. Regarding the percentage of NBF, five studies were not included in the network meta-analysis because the biopsies were performed after a long period of bone healing (more than 6 months). A total of 31 studies analysed the quantity of residual biomaterial in the histomorphometric findings5–10,13,14,24–28,30–33,35,36,38–40,43–46, 48–53 , and 21 articles analysed the percentage of soft tissues or other tissue in core biopsy6,9,13,14,27,28,30–32,35,38–40,43–45,47–51. Due to the high methodological heterogeneity, this secondary outcome (percentage soft tissue) was not subjected to metaanalysis. A summary of the findings is presented in Table 1. A network meta-analysis was accomplished for 33 studies that analysed different types of grafting materials used for alveolar preservation5–11,13,14,24,26, 28–35,37–44,46,48–52 . All core biopsies were obtained between 3 and 6 months after extraction. Fig. 3 shows the network of eligible comparisons for the percentage of NBF (Fig. 3A) and the percentage of residual biomaterial (Fig. 3B) on histomorphometric analysis. Fig. 4 shows the network meta-analysis results for the primary outcome of NBF. In terms of efficacy, none of the grafting materials produced a significant effect on the percentage of NBF. Eight grafting materials (Bio-Oss, Salvin, Puros, Bio-Oss Collagen, Endobon, enamel matrix derivatives, FDBA, and enamel matrix derivatives plus bone ceramic) statistically reduced the quantity of NBF in the histomorphometric analysis. The effect difference between two different modalities of treatment, obtained from direct and indirect evidence, is shown in Fig. S1 in the Supplementary Material. The present arm-based network meta-analysis allowed rankograms of the percentage of NBF and the percentage of residual biomaterial to be obtained (Fig. 5). The biomaterial with the highest amount of NBF was plasma rich in growth factors (PRGF). The combination of platelet-rich fibrin (PRF) and AlloOss reabsorbed faster than other grafting materials. This combination had the highest probability of being in the first rankogram position. Discussion

Numerous grafting materials have been proposed to minimize bone loss after tooth extraction5–11,13,14,24–52. Studies have

shown that alveolar ridge preservation techniques, after tooth extraction, can be an effective therapy to prevent bone loss19,53. Nevertheless, a certain quantity of ridge loss should be expected even if alveolar ridge preservation is utilized19. Many factors may influence alveolar bone loss after tooth extraction. These include the number of neighbouring teeth to be extracted, socket morphology, periodontal biotype (i.e., soft tissue thickness and buccal plate), smoking status, and systemic diseases18. This network meta-analysis addressed the histomorphometric data of 34 interventions for alveolar ridge preservation, including 33 different grafting materials and blood clot. A thorough, objective, and reproducible search of a range of sources EMBASE, (MEDLINE/PubMed, Cochrane Library, Web of Science, Scopus, LILACs, and the grey literature) to identify as many relevant studies as possible was accomplished. A limited number of studies comparing a large number of biomaterials were found, which clearly decreases the quality level of a body of evidence. However, this is the most extensive evidence on this topic and can be used to guide future comparisons. This analysis was based on 1268 tooth extractions in 985 patients. The present study did not attempt to evaluate width or height changes obtained with different biomaterials, as was done in some previous studies19,53,54. Our results differ in part from those presented in other previous systematic reviews, in which bone measurement was the focus of research, and different commercial biomaterials were included in the same category during the analysis14,40,53. It has been suggested that the same biomaterial may present different performance in NBF, if different manufacturing processes are used13. Cook and Mealey14 compared two xenograft biomaterials and found a statistical difference in terms of the percentage of bone formation in histomorphometric parameters. The head-tohead analysis accomplished in the present network meta-analysis showed no statistical difference in the percentage of NBF among bone substitute biomaterials originating from the same source (i.e., xenograft, or allograft, or alloplast). Although some differences may be seen in their biological behaviour, there was no influence on the quantity of NBF in the histomorphometric analysis after an adequate period of healing. This systematic review showed that none of the grafting materials had a statistically significant effect in favour of

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

First author, year

Comparison

Site characteristics (tooth/dental arch)

Treatment by group

Staining method

Corning and Mealey, 20199

Allograft vs. allograft Alloplast vs. xenograft vs. control

Shim et al., 201810

Alloplast + rhBMP-2 vs. xenograft

NR

Clark et al., 201852

Platelet concentrate vs. platelet concentrate + allograft vs. allograft vs. control

Non-molar teeth (Mx and Md)

Serrano Mendez et al., 201751

Allograft vs. xenograft

Nart et al., 20176

Xenograft vs. xenograft

Non-molar teeth (Mx and Md) Non-molar teeth (Mx and Md) Premolar and molar teeth (Mx and Md)

20 17 11 11 10 10 10 10 10 10 10 10 10 11 11 30 30 30 19 21 10 10 10 10 20 20 10 10

HE

Machtei et al., 20197

Anterior + premolar (Mx and Md) 29 premolar, 2 canine, 2 incisor (16 Md, 17 Mx)

Barone et al., 2017

50

Xenograft vs. xenograft

Scheyer et al., 201649

Allograft vs. xenograft

Sadeghi et al., 20168

Allograft vs. xenograft

Milani et al., 20165

Xenograft vs. control

Mayer et al., 201648

Alloplast vs. control

Fernandes et al., 201647

Allograft vs. control

Premolar teeth (Mx and Md) All teeth (Mx and Md) Anterior Mx

Anitua et al., 201511

Platelet concentrate vs. control

Molar Md

Spinato et al., 2014

Allograft vs. control

Collins et al., 201445

Alloplast vs. alloplast + allograft

Calasans-Maia et al., 201444

Xenograft vs. xenograft

Avila-Ortiz et al., 201443

Control vs. allograft

46

Premolar and molar teeth (Mx and Md) NR

Xenograft vs. xenograft

Barone et al., 201342

Xenograft vs. xenograft

Premolar or molar

Alkan et al., 201341

Xenograft vs. EMD

Single-rooted teeth (Mx)

Wood and Mealey, 201240

Allograft vs. allograft

Non-molar teeth

Toloue et al., 201239

Alloplast vs. allograft

Non-molar teeth

14

21 PRGF 5 No grafting 19 Allograft 12 No grafting 9 Alloplast 9 Alloplast + allograft 10 Bio-Oss 10 Osseus 5 No grafting 15 Allograft 21 Bio-Oss Collagen 19 Ossix 31 Bio-Oss 31 Endobon 9 Bio-Oss Collagen 9 EMD 16 DFDBA 16 FDBA 13 CS 15 FDBA

HE HE HE

HE HE HE Azure II and pararosaniline HE HE HE Stevenel’s blue + Alizarin red S and Toluidine blue HE and MGG Toluidine blue or Gomori trichrome Stevenel’s blue + Van Gieson HE and Masson’s trichrome HE HE Stevenel’s blue + Van Gieson HE + Van Gieson trichrome HT Stevenel’s blue + Van Gieson

5

Cook and Mealey, 2013

10 incisor, 3 canine, 18 bicuspid (Mx) 3 incisor, 3 canine, 5 molar (Mx) 1 incisor, 2 canine, 4 molar (Md) 2 incisor, 2 bicuspid, 3 molar (Mx) 12 molar, 1 bicuspid (Md) 9 incisor, 1 canine, 8 bicuspid (Mx) 2 bicuspid (Md) Non-molar teeth

FDBA SDBA BCS Bio-Oss No grafting HA + rh-BMP-2 Bio-Oss A-PRF A-PRF + FDBA FDBA No grafting FDBA Bio-Oss Collagen Bio-Oss Bio-Oss Collagen CPB CCPB No grafting FDBA Bio-Oss Collagen FDBA Bio-Oss Bio-Oss No grafting BCS + b-TCP + HA No grafting Allograft No grafting

Grafting materials in alveolar preservation

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

Table 1. Primary and secondary outcomes.

Site characteristics (tooth/dental arch)

Treatment by group

Staining method

Xenograft vs. control

Anterior Mx

Kutkut et al., 201237

Platelet concentrate + alloplast vs. control

Stevenel’s blue + Alizarin red S HE

Gholami et al., 201236

Alloplast vs. xenograft

7 anterior Mx, 6 posterior Mx, 3 posterior Md Non-molar teeth

Cardaropoli et al., 201235

Xenograft vs. control

16 premolar, 32 molar

Xenograft vs. xenograft + platelet concentrate vs. enamel matrix derivate vs. enamel matrix derivate + bone ceramic

NR

Heberer et al., 201133

Xenograft vs. control

Crespi et al., 201132

Xenograft vs. control Alloplast vs. xenograft vs. control

10 anterior Mx, 12 premolar Mx, 3 molar Mx, 14 molar Md 8 premolar Mx, 9 premolar Md, 7 molar Mx, 6 molar Md Molar and premolar

Checchi et al., 201130

Alloplast vs. alloplast

NR

Pelegrine et al., 201029

Autologous bone marrow vs. control

Anterior Mx

Crespi et al., 200913

Alloplast vs. alloplast vs. control

Molar and premolar

Neiva et al., 200828

Xenograft vs. control

Premolar Mx

Barone et al., 200827

Xenograft vs. control Alloplast + allograft vs. xenograft

15 premolar Mx, 10 premolar Md, 3 canine Mx, 5 canine Md, 7 incisor Mx Non-molar

Froum et al., 200425

Alloplast vs. xenograft

NR

Iasella et al., 200324

Allograft vs. control

NR

10 ABM/P-15 10 No grafting 8 MGCSH + PRP 8 control 15 NanoBone 15 Bio-Oss 24 Bio-Oss 24 control 4 Bio-Oss Collagen 4 Bio-Oss Collagen + PDGF 4 EMD 4 EMD + bone ceramic 20 Bio-Oss Collagen 19 control 15 Tecnoss 15 control 15 Sint 15 Tecnoss 15 control 5 Sint 5 Ostim 16 Autologous 14 control 15 Sint 15 Easy Set 15 control 12 ABM/P-15 12 control 20 CCPB 20 No grafting 12 CS + DFDBA 12 Bio-Oss 8 Alloplast 8 Bovine bone 12 Allograft 10 control

Nevins et al., 2011

Crespi et al., 2011

Vance et al., 2004

34

31

26

HE Azure II and pararosaniline Toluidine blue/pyronine G HE Toluidine blue Toluidine blue HE + Giemsa + Goldner’s trichrome HE Toluidine blue HE Fast green and acid fuchsin HE Stevenel’s blue + Van Gieson HE

Canellas et al.

Comparison

Novaes Jr et al., 201238

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Table 1 (Continued ) First author, year

New bone formation (%) Mean
SD Corning and Mealey, 2019 Shim et al., 2018

YIJOM-4305; No of Pages 14

Primary outcome

9

10

Machtei et al., 20197 Clark et al., 201852

Serrano Mendez et al., 201751 Nart et al., 20176 Barone et al., 201750 Scheyer et al., 201649 Sadeghi et al., 20168 Milani et al., 20165 Mayer et al., 2016

48

Fernandes et al., 201647 Anitua et al., 201511 Spinato et al., 201446 Collins et al., 201445 Calasans-Maia et al., 201444

FDBA (24.08
12.49) SDBA (27.19
17.50) HA + rhBMP-2 (25.37
17.23) Bio-Oss (6.13
4.32) BCS (44.15
18.80) Bio-Oss (22.50
24.72) Control (81.72
4.30) A-PRF (46.00
18.00) A-PRF + FDBA ffi(39.00
13.00) FDBA (29.00
14.00) Control ffi(40.00
15.00) FDBA (29.00
14.00) Bio-Oss Collagen (35.5
16.80) Bio-Oss (33.44
17.82) Bio-Oss Collagen (37.68
13.38) CPB (36.80
19.10) CCPB (41.40
20.60) Control (44.0
14.70) FDBA (33.36
11.09) Bio-Oss Collagen (26.81
9.03) FDBA (34.49
3.19) Bio-Oss (18.76
3.54) Bio-Oss (14.60
12.2) Control (30.6
13.4) BCS + b-TCP + HA (47.7
10.6) No grafting (52.6
11.6) Allograft (43.29
6.41) No grafting (35.99
9.65) PRGF (63.10
13.80) No grafting (35.60
35.3) Allograft (20.53
15.30) No grafting (22.57
7.05) Alloplast (33.00
9.00) Alloplast + allograft (31.00
19.00) Bio-Oss (19.30
22.6) Osseus (33.60
7.1)

Secondary outcomes P-valuea

Meta-analysis

0.53

Yes

0.048*

Yes

<0.05*

Yes

<0.05*

Yes

0.112

Yes

0.89

Yes

NR

Yes

0.17

Yes

0.004*

Yes

NR

Yes

0.76

Yes

0.038*

Residual biomaterial (%) Mean
SD

P-valuea

Soft tissue/other (%) Mean
SD

P-valuea

Meta-analysis

0.41

Yes

>0.05

FDBA (52.95
13.86) SDBA (49.14
11.87) NR

>0.05

Yes

0.486

NR

NR

Yes

>0.05

NR

NR

Yes

>0.05

0.222

Yes

0.89

Yes

–

Yes

0.25

Yes

0.005*

FDBA (16.50
12.1) Bio-Oss Collagen (22.80
13.70) Bio-Oss (53.88
17.43) Bio-Oss Collagen (50.31
19.20) CPB (47.80
19.20) CCPB (41.40
15.90) Control (56.0
14.70) FDBA (53.66
7.62) Bio-Oss Collagen (50.77
8.26) NR

–

Yes

–

NR

–

Yes

–

0.03*

Yes

0.404

No

–

Yes

No

FDBA (22.96
9.03) SDBA (23.38
13.45) HA + rhBMP-2 (12.03
8.03) Bio-Oss (16.79
1.46) BCS (16.51
16.20) Bio-Oss (40.18
17.20) Control (0
0) A-PRF (0
0) A-PRF + FDBA ffi(3.00
3.00) FDBA (11.00
9.00) Control ffi(0
0) FDBA (33.80
9.4) Bio-Oss Collagen (22.2
13.40) Bio-Oss (13.14
8.32) Bio-Oss Collagen (16.00
11.60) CPB (15.50
8.40) CCPB (14.90
7.30) Control (0
0) FDBA (12.78
6.60) Bio-Oss Collagen (19.40
10.99) FDBA (6.06
1.02) Bio-Oss (12.77
1.85) Bio-Oss (33.4
27.20) Control (0
0) BCS + b-TCP + HA (15.99
11.4) No grafting (0
0) NR

–

0.049*

Yes

NR

–

BCS + b-TCP + HA (36.3
19.4) No grafting (46.7
10.6) Allograft (38.66
7.72) No grafting (35.51
10.07) NR

NR

Yes

–

NR

–

Yes

0.7

No

0.06

No

Yes

Alloplast ffi(48.00
24.00) Alloplast + allograft ffi(55.00
10.00) Bio-Oss (49.9
14.1) Osseus (32.3
8.9)

0.38

>0.05

Allograft (22.75
13.33) No grafting (0
0) Alloplast ffi(21.00
15.00) Alloplast + allograft ffi(7.00
4.00) Bio-Oss (22.6
7.9) Osseus (10.7
16.2)

>0.05

Yes

0.91

0.75 – 0.02*

>0.05

Grafting materials in alveolar preservation

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

Results of histomorphometric analysis

Author names

7

Results of histomorphometric analysis Primary outcome New bone formation (%) Mean
SD

Avila-Ortiz et al., 2014

43 14

Cook and Mealey, 2013 Barone et al., 201342 Alkan et al., 201341

Wood and Mealey, 201240 Toloue et al., 201239 Novaes Jr et al., 201238 37

Kutkut et al., 2012

Gholami et al., 201236 Cardaropoli et al., 201235 Nevins et al., 201134

Heberer et al., 201133 Crespi et al., 201132 Crespi et al., 2011

31

Checchi et al., 201130 Pelegrine et al., 201029

Control (46.40
17.45) Allograft (39.60
13.16) Bio-Oss Collagen (32.83
14.72) Ossix (47.03
9.09) Bio-Oss (31.40
18.10) Endobon (28.50
20.0) Bio-Oss Collagen (28.80
16.14) EMD (34.57
25.67) DFDBA (38.42
14.48) FDBA (24.63
13.65) CS (30.92
8.87) FDBA (16.40
11.20) ABM/P-15 (29.13
6.60) No grafting (38.66
6.90) MGCSH + PRP (38.3
9.30) No grafting (66.5
10.4) NanoBone (28.63
12.53) Bio-Oss (27.35
12.39) Bio-Oss (26.34
16.91) No grafting (43.82
12.23) Bio-Oss Collagen (28.30
17.20) Bio-Oss Collagen + PDGF (39.6
11.30) EMD (23.90
9.30) EMD + bone ceramic (21.4
4.20) Bio-Oss Collagen (24.40
10.80) Control (44.21
24.88) Tecnoss (39.60
9.40) Control (29.5
5.00) Sint (36.5
2.60) Tecnoss (38.0
16.20) Control (30.3
4.80) Sint (49.00
28.00) Ostim (54.0
22.00) Autologous (45.47
7.21) Control (42.87
11.33)

Secondary outcomes P-valuea

Meta-analysis

NR

Yes

<0.001*

Yes

>0.05

Residual biomaterial (%) Mean
SD

Yes

Control (0
0) Allograft (0
0) Bio-Oss Collagen (13.44
11.57) Ossix (0
0) NR

>0.05

Yes

0.010*

Yes

NR

Yes

0.03*

Yes

<0.05*

Yes

0.68

Yes

NR

No

0.18

Yes

<0.05*

Yes

<0.05*

Yes

<0.05*

Yes

0.77

Yes

>0.05

Yes

P-valuea

Soft tissue/other (%) Mean
SD

P-valuea

Meta-analysis

NR

Yes

0.763

Yes

–

Control (53.60
17.44) Allograft (36.75
14.60) Bio-Oss Collagen (57.73
6.76) Ossix (52.97
9.09) NR

–

No

NR

–

NR

–

No

DFDBA (8.88
12.83) FDBA (25.42
17.01) CS (2.54
4.67) FDBA (21.37
11.53) ABM/P-15 (20.67
NR) No grafting (0
0) NR

0.004*

–

Yes

NR

Yes

0.03*

Yes

–

DFDBA (52.71
7.96) FDBA (49.94
11.07) CS (64.98
11.83) FDBA (61.55
8.92) ABM/P-15 (42.4
4.2) No grafting (54.5
6.5) NR

–

No

NanoBone (13.68
8.07) Bio-Oss (20.62
9.91) Bio-Oss (18.46
11.18) No grafting (0
0) NR

0.058

NR

–

No

–

>0.05

Yes

–

Bio-Oss (55.19
11.45) No grafting (56.17
12.23) NR

–

No

Bio-Oss Collagen (14.75
6.98) Control (0
0) Tecnoss (34.4
5.1) Control (0
0) Sint (32.2
3.2) Tecnoss (36.6
4.80) Control (0
0) Sint (14
7) Ostim (8
7) –

–

NR

–

Yes

–

Tecnoss (26.0
9.9) Control (57.7
6.9) Sint (33.3
1.50) Tecnoss (25.3
9.40) Control (58.3
7.1) Sint (7
9) Ostim (3
5) NR

<0.05*

Yes

<0.05*

Yes

0.58

Yes

–

No

NR –

NR –

– 0.21 –

Canellas et al.

Author names

YIJOM-4305; No of Pages 14

8

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

Table 1 (Continued )

YIJOM-4305; No of Pages 14

Yes NR

Yes <0.05*

No

No <0.05*

NR

Yes >0.05

Iasella et al., 200324

Froum et al., 2004

25

Vance et al., 200426

Barone et al., 200827

Neiva et al., 200828

ABM/P-15, anorganic bone matrix cell-binding peptide P-15; A-PRF, advanced platelet-rich fibrin; BCS, biphasic calcium sulphate; CCPB, collagenated corticocancellous porcine bone; CPB, cortical porcine bone; CS, calcium sulphate; DFDBA, demineralized freeze-dried bone allograft; EMD, enamel matrix derivatives; FDBA, freeze-dried bone allograft; HA, hydroxyapatite; HE, haematoxylin and eosin; HT, haematoxylin and treosin; ICB, iliac crest bone; MGCSH, medical-grade calcium sulphate hemihydrate; MGG, May– Gru¨nwald–Giemsa stain; Mx, maxilla teeth; NR, not reported; PDGF, platelet-derived growth factor; PRGF, plasma rich in growth factors; PRP, platelet-rich plasma; rhBMP-2, recombinant human bone morphogenetic protein type 2; SD, standard deviation; SDBA, solvent dehydrated bone allograft; b-TCP, beta-tricalcium phosphate. a Asterisks indicate significance; *P < 0.05.

Yes –

No – NR

NR –

<0.05*

–

NR

Yes –

No <0.05*

Yes >0.05 –

Yes Crespi et al., 200913

Sint (40.00
2.70) Easy Set (45.00
6.50) Control (32.80
5.8) ABM/P-15 (29.92
8.46) No grafting (36.54
7.73) CCPB (35.50
10.40) Control (25.70
9.5) CS + DFDBA (61.0
9.00) Bio-Oss (26.00
20.00) Alloplast (31.05
13.67) Bovine bone (29.76
18.07) Allograft (28.00
14.00) Control (54
12.00)

<0.05*

Sint (20.2
3.20) Easy Set (13.90
3.40) Control (0
0) ABM/P-15 (6.25
NR) No grafting (0
0) CCPB (29.2
10.1) Control (0
0) CS + DFDBA (3
3) Bio-Oss (16.0
7.0) Alloplast (11.31
10.03) Bovine bone (17.15
11.38) Allograft (37.00
18.00) Control (0
0)

<0.05*

Sint (41.30
1.30) Easy Set (41.50
6.70) Control (64.60
6.80) ABM/P-15 (65.25
6.41) No grafting (62.67
7.41) CCPB (36.60
12.60) Control (59.10
10.40) NR

<0.05*

Yes

Grafting materials in alveolar preservation

9

NBF. The two grafts most studied by histomorphometric analysis were BioOss and Bio-Oss Collagen. Both of these biomaterials reduced the percentage of NBF after the initial alveolar healing period (from 3 to 6 months after tooth extraction). Similarly, after the same period, a large quantity of residual graft was observed. They had a higher probability of being ranked in the lowest 10 positions in the rankogram. This means that these biomaterials have a slow resorption process. This can be interpreted in two ways. On the one hand, biomaterials with slow resorption characteristics could be more useful in maintaining the socket dimensions after tooth extraction18. On the other hand, the amount of residual graft material may have a negative impact on primary implant stability and subsequent successful osseointegration19. In addition, the head-to-head analysis showed no statistical difference in the percentage of residual graft particles. The exception was the combination of PRF and AlloOss. Some articles have suggested the use of PRF in oral surgical procedures, due to its biological potential to improve wound healing12,55,56. PRF appears to be an important reservoir of growth factors to promote angiogenesis, such as vascular endothelial growth factor (VEGF) and transforming growth factor beta (TGF-b). In agreement, this network meta-analysis showed a beneficial effect of PRF on the reduction of graft particles during initial alveolar healing, assuming a higher probability of being in the first rank position among the options. The best grafting material in NBF was PRGF. This biomaterial resorbs quickly, allowing new trabecular bone formation through its biological properties. However, two important points should be considered. First, the capacity of this graft to preserve alveolar bone dimensions was not measured, since this analysis focused on histomorphometric data. Second, only one RCT evaluating PRGF was found11. The authors performed 60 extractions, but only 26 biopsy specimens were analysed. This raises the possibility that effect estimates are biased. Studies with complete outcome data are needed to improve the quality of evidence. An important consideration is that the present study did not address how the biomaterials behaved in terms of alveolar bone preservation, since the ridge volume was not measured. Therefore, it was not possible to determine which biomaterial can be considered the best. The fact that Bio-Oss demonstrated reduced bone formation on histomorphometric analysis,

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

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Canellas et al.

Fig. 3. Network meta-analysis of eligible comparisons for (A) the percentage of new bone formation, and (B) the percentage of residual graft particles. The size of each node is proportional to the number of direct comparisons made. The number represents the sample size. The lines between intervention nodes indicate the comparisons made within randomized clinical trials. The width of the lines is proportional to the number of trials comparing each pair of interventions. If there is no line between two nodes, then no studies directly compared the two grafting materials.

does not indicate how this grafting material behaves in alveolar ridge preservation, or what the percentage of NBF is after a longer period of bone healing. We believe that a good choice after tooth extraction is a combination of one biomaterial that acts to improve socket preservation, such

as Bio-Oss35, and another biomaterial that acts to improve the percentage of NBF, such as PRF52. In relation to the duration of the healing period, no statistically significant heterogeneity was observed among the studies that evaluated NBF at 3, 4, or 6 months.

However, studies with periods of more than 7 months showed a higher heterogeneity in the percentage of NBF; therefore, a post hoc analysis determined not to combine these studies in the present network meta-analysis. The different time frames of 3, 4, and 6 months could be

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

Grafting materials in alveolar preservation

11

Fig. 4. Forest plot of the network meta-analysis. The unit of measurement is the percentage of new bone formation in core biopsies. Note that the 95% confidence intervals for Bio-Oss, Salvin, Puros, Bio-Oss Collagen, Endobon, enamel matrix derivatives, FDBA, and enamel matrix derivatives plus bone ceramic do not intersect with the vertical line at zero; this line indicates no statistically significant difference between the tested grafting material and an empty socket without filling. When the confidence intervals are entirely on the negative side, this means that these grafting materials reduce the quantity of new bone formation significantly.

included in this network meta-analysis without the introduction of a confounding factor. Similarly, the authors of another systematic review evaluating histomorphometric outcomes of different grafting materials in sinus floor elevation, considered that the effect of different follow-ups could be negligible57. Some limitations of the present network meta-analysis should be acknowledged.

As stated previously, a limited number of biopsies were analysed in several interventions. Some studies did not collect bone from all included patients. Hence, it is essential to consider the reasons for missing data as well as the quantity of missing data, and their potential impact on the outcome measured. It is possible that the small number of biopsies limited the potential external validity of the results.

Another important issue is selection bias. Randomization combined with allocation concealment should be sufficiently described to prevent selection bias. Few of the studies had a low risk of bias related to the randomization process6,7,41,50–52. Another potential source of bias, as mentioned previously, is the low number of studies evaluating a specific material, as well as the different methods of

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

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Canellas et al.

Fig. 5. Rankogram of the network meta-analysis for (A) the percentage of new bone formation, and (B) the percentage of residual graft particles. In the plots, each vertical bar represents the probabilities that the grafting material has different possible ranks. A black area indicates the probability of having a higher rank; thus, the darker areas show the probabilities of having the best treatment.

histological evaluation and the different primary endpoints. Notwithstanding these limitations, the findings of this study represent the most comprehensive evidence currently available on the histomorphometric performance (NBF and residual graft particles) of different grafting materials. Finally, limitations related to human factors could have influenced the results, such as variability in demographic factors (e.g., age, sex, and ethnicity). Differences in the surgical procedure performed to obtain the core biopsy, such as different sizes of core, dimensions, and positions (lateral or vertical orientation), the amount of native bone and grafted bone, and the different healing periods analysed should be considered as additional limitations. In summary, this systematic review suggests that there is no available grafting material able to improve the percentage of NBF between 3 and 6 months after tooth extraction. Although the best grafting material in NBF was found to be PRGF, and the combination of PRF and AlloOss was found to resorb faster than the other biomaterials, the biological variation was relatively low among the different grafting materials. The head-to-head comparison

found no statistical difference among bone substitute biomaterials originating from the same source. The data collected and synthesized in this network meta-analysis could be used as a guide for future comparisons of different grafting materials for socket filling. RCTs are the building blocks of systematic reviews, and until there are more studies with a low risk of bias, with more consistency in evaluation methods for ridge preservation, and with less heterogeneity, the conclusions of the present systematic review will remain limited to determine with certainty which is the best biomaterial. Therefore, further RCTs are needed for definitive conclusions. Funding

None. Competing interests

None declared. Ethical approval

Not required.

Patient consent

Not required.

Appendix A. Supplementary data

Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.ijom.2019. 10.007.

References 1. Araujo MG, Lindhe J. Dimensional ridge alterations following tooth extraction. An experimental study in the dog. J Clin Periodontol 2005;32:212–8. 2. Chappuis V, Engel O, Reyes M, Shahim K, Nolte LP, Buser D. Ridge alterations postextraction in the esthetic zone: a 3D analysis with CBCT. J Dent Res 2013;92(12 Suppl):195S–201S. 3. Scala A, Lang NP, Schweikert MT, de Oliveira JA, Rangel-Garcia Jr I, Botticelli D. Sequential healing of open extraction sockets. An experimental study in monkeys. Clin Oral Implants Res 2014;25:288–95.

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

Grafting materials in alveolar preservation 4. Cardaropoli G, Araujo M, Lindhe J. Dynamics of bone tissue formation in tooth extraction sites. An experimental study in dogs. J Clin Periodontol 2003;30:809–18. 5. Milani S, Dal Pozzo L, Rasperini G, Sforza C, Dellavia C. Deproteinized bovine bone remodeling pattern in alveolar socket: a clinical immunohistological evaluation. Clin Oral Implants Res 2016;27:295–302. 6. Nart J, Barallat L, Jimenez D, Mestres J, Gomez A, Carrasco MA, Violant D, RuizMagaz V, et al. Radiographic and histological evaluation of deproteinized bovine bone mineral vs. deproteinized bovine bone mineral with 10% collagen in ridge preservation. A randomized controlled clinical trial. Clin Oral Implants Res 2017;28:840–8. 7. Machtei EE, Mayer Y, Horwitz J, ZigdonGiladi H. Prospective randomized controlled clinical trial to compare hard tissue changes following socket preservation using alloplasts, xenografts vs no grafting: clinical and histological findings. Clin Implant Dent Relat Res 2019;21:14–20. 8. Sadeghi R, Babaei M, Miremadi SA, Abbas FM. A randomized controlled evaluation of alveolar ridge preservation following tooth extraction using deproteinized bovine bone mineral and demineralized freezedried bone allograft. Dent Res J (Isfahan) 2016;13:151–9. 9. Corning PJ, Mealey BL. Ridge preservation following tooth extraction using mineralized freeze-dried bone allograft compared to mineralized solvent-dehydrated bone allograft. A randomized controlled clinical trial. J Periodontol 2019;90:126–33. 10. Shim JY, Lee Y, Lim JH, Jin MU, Lee JM, Suh JY, Kim YG. Comparative evaluation of recombinant human bone morphogenetic protein-2/hydroxyapatite and bovine bone for new bone formation in alveolar ridge preservation. Implant Dent 2018;27:623–9. 11. Anitua E, Murias-Freijo A, Alkhraisat MH, Orive G. Clinical, radiographical, and histological outcomes of plasma rich in growth factors in extraction socket: a randomized controlled clinical trial. Clin Oral Investig 2015;19:589–600. 12. Canellas J, Medeiros PJD, Figueredo C, Fischer RG, Ritto FG. Platelet-rich fibrin in oral surgical procedures: a systematic review and meta-analysis. Int J Oral Maxillofac Surg 2019;48:395–414. 13. Crespi R, Cappare P, Gherlone E. Magnesium-enriched hydroxyapatite compared to calcium sulfate in the healing of human extraction sockets: radiographic and histomorphometric evaluation at 3 months. J Periodontol 2009;80:210–8. 14. Cook DC, Mealey BL. Histologic comparison of healing following tooth extraction with ridge preservation using two different xenograft protocols. J Periodontol 2013;84: 585–94. 15. Kobayashi E, Fluckiger L, Fujioka-Kobayashi M, Sawada K, Sculean A, Schaller B,

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

Miron RJ. Comparative release of growth factors from PRP, PRF, and advanced-PRF. Clin Oral Investig 2016;20:2353–60. Cipriani A, Higgins JP, Geddes JR, Salanti G. Conceptual and technical challenges in network meta-analysis. Ann Intern Med 2013;159:130–7. Salanti G, Higgins JP, Ades AE, Ioannidis JP. Evaluation of networks of randomized trials. Stat Methods Med Res 2008;17:279–301. Avila-Ortiz G, Elangovan S, Kramer KW, Blanchette D, Dawson DV. Effect of alveolar ridge preservation after tooth extraction: a systematic review and meta-analysis. J Dent Res 2014;93:950–8. Morjaria KR, Wilson R, Palmer RM. Bone healing after tooth extraction with or without an intervention: a systematic review of randomized controlled trials. Clin Implant Dent Relat Res 2014;16:1–20. Bassir SH, Alhareky M, Wangsrimongkol B, Jia Y, Karimbux N. Systematic review and meta-analysis of hard tissue outcomes of alveolar ridge preservation. Int J Oral Maxillofac Implants 2018;33:979–94. Iocca O, Farcomeni A, Lopez SP, Talib HS. Alveolar ridge preservation after tooth extraction: a Bayesian Network meta-analysis of grafting materials efficacy on prevention of bone height and width reduction. J Clin Periodontol 2017;44:104–14. Moher D, Liberati A, Tetzlaff J, Altman DG. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339: b2535. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. Iasella JM, Greenwell H, Miller RL, Hill M, Drisko C, Bohra AA, Scheetz JP. Ridge preservation with freeze-dried bone allograft and a collagen membrane compared to extraction alone for implant site development: a clinical and histologic study in humans. J Periodontol 2003;74:990–9. Froum S, Cho SC, Elian N, Rosenberg E, Rohrer M, Tarnow D. Extraction sockets and implantation of hydroxyapatites with membrane barriers: a histologic study. Implant Dent 2004;13:153–64. Vance GS, Greenwell H, Miller RL, Hill M, Johnston H, Scheetz JP. Comparison of an allograft in an experimental putty carrier and a bovine-derived xenograft used in ridge preservation: a clinical and histologic study in humans. Int J Oral Maxillofac Implants 2004;19:491–7. Barone A, Aldini NN, Fini M, Giardino R, Guirado JLC, Covani U. Xenograft versus extraction alone for ridge preservation after tooth removal: a clinical and histomorphometric study. J Periodontol 2008;79:1370–7. Neiva RF, Tsao YP, Eber R, Shotwell J, Billy E, Wang HL. Effects of a putty-form

29.

30.

31.

32.

33.

34.

35.

36.

37.

38.

13

hydroxyapatite matrix combined with the synthetic cell-binding peptide P-15 on alveolar ridge preservation. J Periodontol 2008;79:291–9. Pelegrine AA, da Costa CE, Correa ME, Marques Jr JF. Clinical and histomorphometric evaluation of extraction sockets treated with an autologous bone marrow graft. Clin Oral Implants Res 2010;21:535–42. Checchi V, Savarino L, Montevecchi M, Felice P, Checchi L. Clinical-radiographic and histological evaluation of two hydroxyapatites in human extraction sockets: a pilot study. Int J Oral Maxillofac Surg 2011;40:526–32. Crespi R, Cappare P, Gherlone E. Comparison of magnesium-enriched hydroxyapatite and porcine bone in human extraction socket healing: a histologic and histomorphometric evaluation. Int J Oral Maxillofac Implants 2011;26:1057–62. Crespi R, Cappare P, Romanos GE, Mariani E, Benasciutti E, Gherlone E. Corticocancellous porcine bone in the healing of human extraction sockets: combining histomorphometry with osteoblast gene expression profiles in vivo. Int J Oral Maxillofac Implants 2011;26:866–72. Heberer S, Al-Chawaf B, Jablonski C, Nelson JJ, Lage H, Nelson K. Healing of ungrafted and grafted extraction sockets after 12 weeks: a prospective clinical study. Int J Oral Maxillofac Implants 2011;26:385–92. Nevins ML, Camelo M, Schupbach P, Nevins M, Kim SW, Kim DM. Human buccal plate extraction socket regeneration with recombinant human platelet-derived growth factor BB or enamel matrix derivative. Int J Periodontics Restorative Dent 2011;31: 481–92. Cardaropoli D, Tamagnone L, Roffredo A, Gaveglio L, Cardaropoli G. Socket preservation using bovine bone mineral and collagen membrane: a randomized controlled clinical trial with histologic analysis. Int J Periodontics Restorative Dent 2012;32: 421–30. Gholami GA, Najafi B, Mashhadiabbas F, Goetz W, Najafi S. Clinical, histologic and histomorphometric evaluation of socket preservation using a synthetic nanocrystalline hydroxyapatite in comparison with a bovine xenograft: a randomized clinical trial. Clin Oral Implants Res 2012;23: 1198–204. Kutkut A, Andreana S, Kim HL, Monaco Jr E. Extraction socket preservation graft before implant placement with calcium sulfate hemihydrate and platelet-rich plasma: a clinical and histomorphometric study in humans. J Periodontol 2012;83:401–9. Novaes Jr AB, Fernandes PG, Suaid FA, De Moraes Grisi MF, De Souza SLS, Taba Jr M, Palioto DB, Muglia VA. Ridge preservation with acellular dermal matrix and anorganic bone matrix cell-binding peptide P-15 after tooth extraction in humans. A histologic and

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.

YIJOM-4305; No of Pages 14

14

39.

40.

41.

42.

43.

44.

45.

46.

Canellas et al. morphometric study. J Osseointegration 2012;4:23–30. Toloue SM, Chesnoiu-Matei I, Blanchard SB. A clinical and histomorphometric study of calcium sulfate compared with freezedried bone allograft for alveolar ridge preservation. J Periodontol 2012;83:847–55. Wood RA, Mealey BL. Histologic comparison of healing after tooth extraction with ridge preservation using mineralized versus demineralized freeze-dried bone allograft. J Periodontol 2012;83:329–36. Alkan EA, Parlar A, Yildirim B, Senguven B. Histological comparison of healing following tooth extraction with ridge preservation using enamel matrix derivatives versus Bio-Oss Collagen: a pilot study. Int J Oral Maxillofac Surg 2013;42:1522–8. Barone A, Todisco M, Ludovichetti M, Gualini F, Aggstaller H, Torres-Lagares D, Rohrer MD, Prasad HS, Kenealy JN. A prospective, randomized, controlled, multicenter evaluation of extraction socket preservation comparing two bovine xenografts: clinical and histologic outcomes. Int J Periodontics Restorative Dent 2013;33:795–802. Avila-Ortiz G, Rodriguez JC, Rudek I, Benavides E, Rios H, Wang HL. Effectiveness of three different alveolar ridge preservation techniques: a pilot randomized controlled trial. Int J Periodontics Restorative Dent 2014;34:509–21. Calasans-Maia M, Resende R, Fernandes G, Calasans-Maia J, Alves AT, Granjeiro JM. A randomized controlled clinical trial to evaluate a new xenograft for alveolar socket preservation. Clin Oral Implants Res 2014;25:1125–30. Collins JR, Jimenez E, Martinez C, Polanco RT, Hirata R, Mousa R, Coelho PG, Bonfante EA, Tovar N. Clinical and histological evaluation of socket grafting using different types of bone substitute in adult patients. Implant Dent 2014;23:489–95. Spinato S, Galindo-Moreno P, Zaffe D, Bernardello F, Soardi CM. Is socket healing

47.

48.

49.

50.

51.

52.

conditioned by buccal plate thickness? A clinical and histologic study 4 months after mineralized human bone allografting. Clin Oral Implants Res 2014;25:e120–6. Fernandes PG, Muglia VA, Reino DM, Maia LP, de Moraes Grisi MF, de Souza SL, Taba Jr M, Palioto DB, de Almeida AG, Novaes Jr AB. Socket preservation therapy with acellular dermal matrix and mineralized bone allograft after tooth extraction in humans: a clinical and histomorphometric study. Int J Periodontics Restorative Dent 2016;36: e16–25. Mayer Y, Zigdon-Giladi H, Machtei EE. Ridge preservation using composite alloplastic materials: a randomized control clinical and histological study in humans. Clin Implant Dent Relat Res 2016;18:1163–70. Scheyer ET, Heard R, Janakievski J, Mandelaris G, Nevins ML, Pickering SR, Richardson CR, Pope B, Toback G, Velasquez D, Nagursky H. A randomized, controlled, multicentre clinical trial of postextraction alveolar ridge preservation. J Clin Periodontol 2016;43:1188–99. Barone A, Toti P, Quaranta A, Alfonsi F, Cucchi A, Negri B, Di Felice R, Marchionni S, Calvo-Guirado JL, Covani JU, Nannmark U. Clinical and histological changes after ridge preservation with two xenografts: preliminary results from a multicentre randomized controlled clinical trial. J Clin Periodontol 2017;44:204–14. Serrano Mendez CA, Lang NP, Caneva M, Ramirez Lemus G, Mora Solano G, Botticelli D. Comparison of allografts and xenografts used for alveolar ridge preservation. A clinical and histomorphometric RCT in humans. Clin Implant Dent Relat Res 2017;19:608–15. Clark D, Rajendran Y, Paydar S, Ho S, Cox D, Ryder M, Dollard J, Kao RT. Advanced platelet-rich fibrin and freeze-dried bone allograft for ridge preservation: a randomized controlled clinical trial. J Periodontol 2018;89:379–87.

53. J.V.d.S. Canellas, P.J.D. Medeiros, C.M.d.S. Figueredo, R.G. Fischer, F.G. Ritto, Which is the best choice after tooth extraction, immediate implant placement or delayed placement with alveolar ridge preservation? A systematic review and meta-analysis, J Craniomaxillofac Surgy. https://doi.org/10. 1016/j.jcms.2019.08.004. 54. Atieh MA, Alsabeeha NHM, Payne AGT, Duncan W, Faggion CM, Esposito M. Interventions for replacing missing teeth: alveolar ridge preservation techniques for dental implant site development. Cochrane Database Syst Rev )2015;(5)CD010176. 55. Canellas J, Ritto FG, Medeiros PJD. Evaluation of postoperative complications after mandibular third molar surgery with the use of platelet-rich fibrin: a systematic review and meta-analysis. Int J Oral Maxillofac Surg 2017;46:1138–46. 56. Ritto FG, Pimentel T, Canellas JVS, Junger B, Cruz M, Medeiros PJ. Randomized double-blind clinical trial evaluation of bone healing after third molar surgery with the use of leukocyte- and platelet-rich fibrin. Int J Oral Maxillofac Surg 2019;48:1088–93. 57. Corbella S, Taschieri S, Weinstein R, Del Fabbro M. Histomorphometric outcomes after lateral sinus floor elevation procedure: a systematic review of the literature and metaanalysis. Clin Oral Implants Res 2016;27: 1106–22.

Address: Joa˜o Vitor Canellas Department of Oral and Maxillofacial Surgery Faculty of Dentistry Rio de Janeiro State University Rua Boulevard 28 de Setembro 157 Vila Isabel Rio de Janeiro RJ 20551-030 Brazil Tel.: +55 (021) 971507053 E-mail: [email protected]

Please cite this article in press as: Canellas JVS, et al. Histomorphometric evaluation of different grafting materials used for alveolar ridge preservation: a systematic review and network meta-analysis, Int J Oral Maxillofac Surg (2019), https://doi.org/10.1016/j.