Tooth Graft: An Umbrella Overview

Abstract This umbrella review aims to evaluate systematic/meta-analysis studies containing clinical evidence on tooth grafts as bone substitutes in the oral and maxillofacial regions. Using language restrictions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an electronic database search of PubMed, MEDLINE, Embase, Cochrane library, and Google Scholar was conducted, featuring published studies up until August 2022. All systematic/meta-analysis review articles relating to tooth graft materials were matched against the inclusion criteria. Two qualified researchers independently assessed the studies' inclusion or exclusion criteria and risk of bias, and a third investigator assisted in resolving ambiguities. A total of 81 systematic/meta-analysis studies, comprising 21 animal-controlled trials, 23 randomized controlled human trials, 23 prospective studies, and 14 retrospective studies, were selected for this study. A small risk of bias was observed in systematic studies/meta-analyses. In addition, the clinical evidence from the analysis of these studies revealed a low incidence of side effects. According to the current review, two systematic reviews indicated that autogenous bone grafting of prepared teeth might be as effective as other bone grafting materials. Four studies also mentioned autologous grafts as potential alternatives to autologous grafts, autogenous demineralized dentin (ADDM), engineered grafts, root blocks, and dental matrix. On the other hand, three systematic studies stated that more long-term research is needed to confirm their findings. Finally, given the importance of standardization and homogeneity of studies for clinical cases, it is advised to be used cautiously due to the risks of transplant rejection.

provide predictable conditions and satisfactory results for vertical augmentation 3 .
In the past, bone grafting materials were used to restore the degenerated bone to regenerate alveolar bone due to periodontal diseases, jaw, and facial surgical defects.Increasing advances in dental implantology have led to the development of numerous techniques and procedures, such as bone expansion and sinus floor elevation.Currently, the gold standard for reconstructing hard tissue is an autogenous bone graft. 4evertheless, donor site issues, virus transmission, resorption, limited access, and the creation of surgical sites can be cited as complications associated with this technique.Due to these factors, numerous studies on bone replacement materials, such as mineralized and freeze-dried bone allografts and synthetic alloplastic grafts, have been conducted. 5,6][9][10][11][12] The general instructions for preparing transplant materials include extraction of autogenous, allogeneic, or xenogeneic teeth, preparation of soft-tissue and tooth fragmentation, demineralization/remineralization, and sterilization.In addition, several animal studies have reported osteoconductive and osteoinductive effects using dentin as an autograft. 7,13Some RCTs comparing tooth bone grafts to other bone substitutes found comparable outcomes, 9,10 while other studies found no difference. 14In addition, some articles have reported negative side effects, including implant loosening, bone graft failure, and infection. 11,12his umbrella review analyzed nine systematic reviews/meta-analyses (SRs/MAs).Mahardawi et al systematically evaluated oral autogenous bone grafting clinical findings.Their question was: "In partly edentulous individuals, what are the alveolar ridge volume changes, histological findings, and implant durability in locations reinforced using dental autogenous bone grafting?" 15Li et al compared the clinical and histological efficacy of autogenous demineralized dentin matrix (ADDM) as a bone graft material to Bio-Oss in strengthening oral bone lesions. 16azal-Bonelli et al investigated the clinical effects of autogenous tooth root blocks on ridge reinforcement, implant survival, block absorption, postsurgical complications, and histologic outcomes. 17Gharpure and Bhatavadekar conducted a comprehensive analysis to compare tooth bone grafts to other bone replacements in the oral and maxillofacial regions. 18Shavit et al performed a systematic review of sinus augmentation procedures utilizing various tooth-derived bone graft materials and compared the outcomes of dental graft, xenograft, allograft, and alloplastic using radiography and histomorphometry. 19tarch-Jensen et al conducted a systematic review of the clinical data on implant management after lateral alveolar ridge augmentation (LARA) with autogenous dental block grafting versus autogenous bone block grafting before implant placement. 20Inchingolo et al studied engineered structures, such as tooth block grafts, growth factors, and light modulation applications for bone repair therapy. 21amanauskaite et al analyzed clinical data regarding the effect of autogenous teeth on alveolar ridge augmentation. 22azballa et al examined the clinical evidence of a tooth as a material for bone augmentation in alveolar ridges. 23ased on the disparity of results in the literature, this umbrella review aims to evaluate systematic studies with clinical application results of dental bone grafting as a bone substitute in oral and maxillofacial regions.

Method Study Design
The utilized articles included systematic/meta-analysis reviews and resources examining the outcomes of tooth bone grafts.The methodology adhered to the Cochrane Handbook guidelines, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, 18 and several high-quality methodological overviews. 19,20clusion Criteria

Study Type
This overview was limited to SRs/MAs of clinical trials, case controls, and cohorts on using tooth substitutes as bone grafting material in craniofacial regions.

Subject Type
Patients who underwent alveolar ridge grafting with a bone substitute were included, regardless of age, race, or gender.

Intervention Types
In the experimental group, the intervention consisted of using a tooth substitute as a grafting material for alveolar ridge/sinus augmentation.In the control group, the intervention comprised autogenous bone blocks, xenogeneic material, allogenic material, or no grafts.

Outcome Measurement Types
The outcome measurements included implant stability; volumetric bone changes; and clinical, histologic, radiologic, immunological, and biochemical evaluation (►Table 1).
In addition, the following criteria were applied to the articles: (1) systematic reviews of at least two primary studies; (2) a focus on the outcomes of using tooth substitutes as bone graft material in human alveolar ridge/sinus augmentation, (3) systematic reviews comprising longitudinal studies examining the impact of use of tooth substitutes for orofacial bone augmentation and reporting at least one type of histological/radiological/clinical outcomes; and (4) publications in English.
We excluded the following: (1) systematic reviews that included only animal studies, (2) systematic reviews that included the use of tooth substitutes for grafting other parts of the human body besides the orofacial region, (3) systematic reviews or meta-analyses with unclear inclusion/exclusion criteria and (4) fully overlapping datasets, and (5) studies that report results other than those of interest.
A search was conducted in the electronic databases PubMed, MEDLINE, EMBASE, Cochrane library, and Google Tooth Graft: An Umbrella Overview Hashemi et al. 45 Scholar for articles published up until August 15, 2022, considering language restrictions (only English) and PRISMA guidelines.The search was performed using the Mesh medical subject heading and nonmesh terms in simple or multiple conjunctions.The following keywords were used: (dent Ã ) AND (autogen Ã ) AND ("autogenous tooth bone graft" OR ATBG OR autogen OR tooth graft OR autolog OR ADDM OR allogenous OR xenogenous).These filters were applied to the search results: "systematic review" and "meta-analysis."

Data Extraction
►Fig. 1 depicts the data extraction procedure utilized in this study.►Fig. 2 summarizes the different methods and conditions used for preparation of tooth bone graft material reviewed by SRs/MA.►Table 2 details the main characteristics of the studies included.Data extraction from eligible publications was based on systematic/meta-analysis review reports for the tooth bone graft outcomes.Studies were included if they focused on tooth grafting and were in English.Abstracts, review articles, editorial articles, guidelines/protocols, and articles not published with appropriate clinical outcomes were excluded from the study.
Two independent reviewers (M.R. and Q.P.) determined which studies were eligible for analysis (1.0 kappa).One researcher (M.R.) was responsible for extracting qualitative or quantitative data from the studies, while the second researcher (Q.P.) was responsible for validating all qualified information.Information collected included the author's name, the year and type of study, the number of patients, an evaluation of outcomes, a comparison of results, and a conclusion.

Data Analysis
There were significant differences between eligible articles regarding participant inclusion criteria, populations, alternative procedures, and follow-up duration (►Table 2), indicating a high degree of heterogeneity among studies.As a result, it is unreasonable to assume that all reviews assessed the same effect.

Bias Risk Assessment
We used 16 questions from the Assessment of Multiple Systematic Reviews 2 (AMSR2) 25 tool to assess the quality of systematic/meta-analysis review studies based on the risk of bias assessment (►Fig. 3).Each article was ultimately assigned a score that indicates the likelihood of bias in the study.If 8 to 11 questions were answered positively, the risk of bias was low; if 4 to 7 questions were answered positively, the risk of bias was moderate.The risk of bias was deemed high if fewer than three questions received positive responses. 26Two qualified researchers assessed the articles (kappa ¼ 0.90).Inconsistency and ambiguity were resolved through discussions.The third investigator assisted in resolving unresolved issues.

Screening of Systematic/Meta-Analysis Reviews
The PubMed, MEDLINE, EMBASE, Cochrane library, and Google Scholar databases yielded 50 systematic/meta-analysis review articles.After removing duplicate sources, the titles and abstracts of 29 studies remained to be examined.After thoroughly evaluating these publications, 21 met the eligibility criteria, and their full papers were read.Finally, nine review articles [15][16][17][18][19][20][21][22][23] were selected for data extraction in the present umbrella study.►Fig. 1 and ►Table 2 detail the research strategy and summarize the most important characteristics of the articles.Regarding the inclusion and exclusion criteria and evaluation of outcomes, the included SRs exhibited a wide range of approaches (►Table 1).There was only a slight overlap between the reviews that utilized tooth grafts (►Table 3).

Evidence Quality
AMSR2 was used to evaluate the risk of bias.The level of bias in the study was classified as high, medium, or low based on the number of correct answers (►Fig.3).The risk of bias in this study (including all systematic and meta-analysis reviews) was low.Clinical evidence consisted of articles with a low risk of bias.To this end, low-risk studies accounted for 100% of the study volume (►Fig.3).

Characteristics of Systematic Reviews
►Tables 1 and 2 provide general information about each systematic/meta-analysis review.In addition, authors and publication year, number and type of studies, type of analysis, interventions, outcomes, bias risk, key findings, inclusion and exclusion criteria, and outcome evaluation of each SR/MA are reported.►Fig. 2 summarizes different methods and conditions used for preparation of tooth bone graft material reviewed by SRs/MA.Mahardawi et al conducted a systematic review that included 20 studies. 15Li et al systematically searched eight databases for RCT studies.The included studies' quality was assessed using the Cochrane Collaboration's risk tool, and the data were analyzed using Stata 15.0 software. 16PRISMA guidelines were used in the study of Bazal-Bonelli et al, and the search was conducted in four databases.The Newcastle-Ottawa Quality Assessment Scale 17 was used to assess the quality of the selected studies.Tooth Graft: An Umbrella Overview Hashemi et al.
In the systematic review conducted by Gharpure and Bhatavadekar, a search was conducted to identify animal and human clinical studies and their risk of bias. 18In the systematic study by Shavit et al, a database search was conducted to identify articles on dental bone grafting in sinus augmentation. 19In a systematic review by Starch-Jensen et al, searches were conducted in three databases.The Cochrane risk of bias tools, the Newcastle-Ottawa scale, and the GRADE system were utilized to evaluate the quality of included studies. 20In the research conducted by Inchingolo et al, four databases were queried. 21In the Ramanauskaite et al systematic review, six studies met the criteria for inclusion.Autogenous teeth were utilized in lateral reinforcement, demineralized dentin matrix, vertical reinforcement of sockets after extraction, and height of the lateral sinus floor. 22n the systematic review by Mahardawi et al, alveolar bone dimensions were reported for heights ranging from -0.64 to þ2.26 mm and widths ranging from -1.21 to þ-0.41 mm.In addition, a significant increase in the dimensions of the additional sites was observed.The survival rate was 98.8% for delayed implant placement and 97.4% for immediate implant placement.Furthermore, utilizing this graft increased the percentage of ossification and bone volume at different time points after surgery. 15i et al performed a systematic review of seven RCTs involving 220 patients.These studies observed an insignificant difference in the amount of new bone formation or implant stability.In addition, sinus height and the percentage of residual graft material were significantly lower in patients who received ADDM grafts than in those who received Bio-Oss grafts. 16n the review by Bazal-Bonelli et al, seven studies involving 136 patients met the inclusion criteria and were examined.Among the patients, 118 were treated with autogenous tooth root blocks (15.99% survival), and 26 were treated with autogenous bone blocks (100% survival).The average bone formation in tooth root blocks was comparable to autologous bone formation.Additionally, the implant survival rate in autogenous tooth root blocks was 98.32%. 17n the systematic review by Gharpure and Bhatavadekar, the inclusion criteria were met by 18 animal-controlled and 8 human RCTs involving 184 patients.High levels of heterogeneity existed between the selected studies.In more than half of the studies (71.42% of clinical studies and 55.56% of animal studies), tooth and bone grafting did not demonstrate a statistically significant difference between the tooth bone graft and the control group.In addition, 50% of clinical trials and 63.33% of animal studies posed a low risk of bias.Moreover, 350 patients exhibited adverse effects (18.86%). 18even articles met the inclusion criteria for the systematic study by Shavit et al.Data extraction was based on the diagnostic tool type, which included residual alveolar height, increased graft height, and absorption height. 19n a review conducted by Starch-Jensen et al, three studies met the criteria for inclusion.Comparing these studies revealed no statistically significant differences between the two treatment methods regarding short-term implant Tooth Graft: An Umbrella Overview Hashemi et al. 51 survival, the health of the tissue surrounding the implant, or the occurrence of complications.In contrast, the tooth block resulted in a significantly narrower alveolar ridge than the bone block.However, short-term mucositis was reported more prevalent around dental implants with dental blocks. 20n the survey performed by Inchingolo et al, 304 articles met the criteria for inclusion.Based on the bone substitute utilized, these articles were divided into alloplastic, autologous, xenograft, platelet-derived, laser therapy, microbiota, and mesenchymal cell groups.21 Hazballa et al concluded that a dental matrix is a viable option for autologous transplantation because it does not cause an antigenic reaction, permits three-dimensional bone reconstruction, is simple to prepare, and is cost-effective.23

Discussion
This umbrella review investigates available evidence regarding using tooth substitutes as bone grafting material in the oral and maxillofacial regions.Due to the availability of numerous recent SRs, it became evident that an umbrella review approach should be adopted to avoid duplication of available evidence and to cover all tooth graft techniques comprehensively.This approach was also supported by the fact that most published SRs considered a variety of tooth graft preparation or outcome evaluation techniques.This heterogeneity prevents most of them from conducting a meta-analysis to determine the extent of this graft's effectiveness.In this umbrella review, 9 15-23 systematic/metaanalysis articles comprising 81 (23 RCTs and 58 non-RCTs) articles were included.The outcomes extracted from these umbrella studies were associated with tooth graft procedures.
All included studies stated that additional long-term research is necessary to confirm their findings.Only one systematic review, which included a meta-analysis, compared the clinical outcomes of demineralized dentin grafts and Bio-Oss and concluded that they are equally effective for augmenting oral bone defects. 16A systematic review on tooth root blocks concluded that reconstruction of alveolar crests using autogenous tooth root blocks appears to be an adequate solution for single-tooth gaps and low grades of bone atrophy in terms of the survival of the bone block and the implants placed afterward. 17ccording to several review articles, the tooth bone graft offers no additional benefits over other graft materials.In addition, the lack of predictability regarding resorption time and clinical success and the lack of standard processing methods restrict the use of this material in clinical practice. 18Others have demonstrated that the bone formation capacity of autogenous tooth graft is comparable to or greater than that of Bio-Oss or the combination of allograft and xenograft, particularly when used in the maxillary sinus. 19Following LARA with autogenous tooth block graft, studies indicate a high short-term implant survival and implant stability index.After 26 weeks of functional implant loading, the peri-implant tissue health following LARA with the two treatment modalities was reported to be comparable.However, a higher incidence of short-term peri-implantitis was observed after LARA with autogenous tooth block grafting. 20he most definitive data for evaluating the osteogenic capability of bone graft material 16 were derived from the histological analysis of human tissue specimens harvested from graft sites.Nevertheless, each study provides a variety of outcome evaluations, such as clinical, radiological, and histological outcomes.Regarding the follow-up duration, SRs did not apply any limitations and the included primary studies showed a variety from 2 weeks to 4 years of follow-up (mostly 6 months).Due to its close proximity to the implant surface, 68,69 the dental matrix shows promise as a biomaterial for preserving the alveolar ridge.The initial condition of the extracted tooth, its combination with other materials (Bio-Oss, Platelet-rich plasma (PRP), Platelet-Rich-Fibrin (PRF)), the size and shape of the particles (ground, sliced, or in block form), treatment (materials used for demineralization and sterilization), composition (enamel, dentin, cementum, pulp, and soft tissue), and graft dimensions were not standardized among the selected studies.
In addition, except for one study 19 that focused solely on sinus augmentation, other studies did not specify the location of the augmented alveolar bone.Inadequate homogeneity and standardization in the processing of graft material make comparisons with other materials more difficult and diminish the graft material's clinical value.In conclusion, it is evident that the reviewed articles displayed significant heterogeneity and that the original studies are inconclusive and require additional research on this topic.However, given the risks of transplant rejection and the difficulty of obtaining autogenous graft material, tooth grafting can be recommended with caution.

Conclusion and Recommendation
Autogenous tooth bone grafts appear to be effective in oral defect reconstructions compared to Bio-Oss, autogenous bone blocks, or no-grafts, despite the heterogeneity of the included SRs and primary studies, as confirmed by the results of the current umbrella overview.There is some evidence that these techniques improve clinical, histological, or radiological outcomes; however, additional research is needed to inform guideline development and to ensure that treatment recommendations are based on long-term clinical outcomes.There is a clear need to increase the emphasis on using tooth bone grafts in managing alveolar ridge resorption as a mainstream option, as the conventional approaches such as Bio-Oss or autogenous bone blocks are prohibited due to cost or surgical site morbidity.

Fig. 1 Fig. 2 A
Fig.1Flowchart for the studies identified, screened, and included in the study.
Tooth Graft: An Umbrella Overview Hashemi et al.49

Table 1
Inclusion and exclusion criteria and outcome evaluation of systematic reviews evaluating tooth graft European Journal of Dentistry Vol.18 No.1/2024 © 2023.The Author(s).Tooth Graft: An Umbrella Overview Hashemi et al.43

Table 1 (
Continued) defect sites of patients in the intervention group were grafted using autogenous demineralized dentin matrix (ADDM) or ATBGs;(5)the control group was given Bio-Oss grafts;(6)at least one osteogenic function-related parameter was measured at both the baseline and follow-up time points outcomes of interest; (4) duplicate studies; and (5) articles with unavailable data Bazal-Bonell et al 17 (1) Clinical human studies of alveolar ridge augmentation with autogenous tooth root block (ATRB) grafting; (2) RCTs, cohort studies, case-control studies, cross-sectional studies, and case series; (3) clinical human studies providing the following data: ATRB survival rate, bone gain, bone resorption, implant survival rates, complications, and histological findings; (4) follow-up of at least 6 mo; (5) number of patients/study arm or cohort greater than five patients; (5) articles published in English, Spanish, or German; (6) no restrictions were imposed on publication dates Exclusion criteria were the following: (1) clinical studies carrying out any other type of ridge augmentation procedure than ATRB grafting; (2) animal studies and case reports; and (3) in vitro studies • Studies evaluating the use of tooth-derived graft materials in the sinus augmentation procedure • Studies evaluating the tooth-derived graft material by at least one of the following diagnostic tools: panoramic radiography, computed tomography, histological or histomorphometric analysis • Studies that assessed the tooth-derived graft material by comparing to control groups receiving sinus grafting with other materials such as xenograft, allograft, and alloplast • Follow-up period of at least 4 mo after grafting for human subjects and 8 wk for animals

Table 2
Baseline characteristics of systematic reviews evaluating tooth graft European Journal of Dentistry Vol.18 No.1/2024 © 2023.The Author(s).Tooth Graft: An Umbrella Overview Hashemi et al.47

Table 3
Primary included studies included in the systematic reviews for using the tooth material as bone grafting material