Various Assisted Bone Regeneration in Apicectomy Defects Systematic Review and Meta Analysis.

INTRODUCTION: In the endodontic surgery, the common applications are the procedures that apply regenerative methods. There are various methods that help in the regeneration after the endodontic root end cutting or apicectomy. The outcome of the apicectomy depends on the procedure and the material. Hence in the present study, we intend to conduct the systemic review and meta-analysis of the various assisted bone regeneration in apicectomy defects.
MATERIALS AND METHODS: The study was conducted by the online search of the data that included the studies for the regenerative procedure in the endodontic surgery in patients with various periapical pathologies. The data search engines were Scopus, Web of Science, Google Scholar, and PubMed. The risk of the bias was calculated. The study participants were divided into case and control groups. Case group had undergone the regenerative surgery for the persistent periapical lesions, while the control group had not undergone the regenerative surgery for the persistent periapical l. The clinical and the radiograph outcomes were compared between the control and the case groups. Meta-analysis was done and the subgroups were evaluated.
RESULTS: From a total of 1561 articles, only 11 were finalized for the study to conduct the meta-analysis. The bias was noted for majority of the studies most of which were clinical trials. It was observed that the regenerative methods used in the endodontic surgery have significantly improved the outcome. The application of the expanded polytetrafluoroethylene only has no significant effect; however, application of the autologous platelet concentrates or collagen membranes only had good outcomes. The combination of the materials showed a significant outcome than when applied alone.
CONCLUSIONS: From this meta-analysis, it is evident that regenerative procedures are beneficial in the endodontic apicectomy procedures. The materials used in these procedures will augment the outcome. A better prognosis is expected if the combination of the materials is used. Copyright:

INTRODUCTION

Prevention is better than cure. It is even better noticed in the dentistry. The preservation of the tooth is better than the replacement. With the enhanced patient motivation and education they prefer for the preservation than the prosthetic replacement.[1] Routine endodontics involves orthograde procedures, but if there is any repeated and resilient infection, the retrograde filling or endodontic surgery is preferred.[2] The periapical tissues repair by either the repair or the regeneration.[3] The repair is by the new tissue and the regeneration is by the original cells. The regeneration is the best method as it will restore the function of the periapical tissue to the previous tissue.[2345] However, the regeneration is difficult to attain. Many procedures have been implemented to attain the regeneration of the apical tissues in the periapical pathologies of the teeth. In the regenerative methods the materials like grafts (bone), autologous platelet concentrates, barriers that act to prevent the growth of the new tissue, etc., are commonly used.[4] The regenerative procedures are implemented in periodontics, endodontic, and implant surgeries. There are materials that are recently reported with better regeneration than the repair in endodontic surgeries. They are bio-absorbable collagen, e-PTFE-non-resorbable expanded polytetrafluoroethylene, etc. These work by preventing the migration of the cells apically and promoting the regeneration.[56]

However, there are various studies that report varying degree of the success using the regenerative methods.[78910111213] Although there are many studies, there have been contrary reports of the success of the regenerative procedures. Also, only a few studies have compared the materials used in these regenerative procedures. Hence in the present study, we intend to conduct a systemic review and meta-analysis of the various assisted bone regeneration in apicectomy defects.

MATERIALS AND METHODS

This meta-analysis was piloted based on the preferred reporting items for systematic reviews and meta-analyses guidelines. The study was conducted for a period of 1 year, and the studies done till March 2021 were included in the meta-analysis.

A literature search was done by the data search engines. They are Scopus, Web of Science, Google Scholar, PubMed. MEDLINE (PubMed), and EMBASE. The ensuing search terms were used: endodontic surgery, root canal treatment (RCT), apicectomy, periapical radiolucency, regenerative procedures, and various regenerative materials such as, GTR, collagen membrane, bone graft, and platelet-rich fibrin. Only human studies were included. The case reports were removed from the study criteria. All the RCTs were included in the study. The language restriction was not considered. The translatable clinical trials were included.

We included only the studies that were

Randomized Controlled trial

Root end surgery for persistent periapical pathology

Persistent periapical radiolucency.

Excluded studies were those where the patients had any medical condition, other periodontal conditions, no thorough follow up data, no materials used for the regeneration materials utilized in the study, the study was poorly designed, the root fracture after the therapy, and short-term follow up for less than an year.

The article selection was done by two reviewers unrelated to each other. The selection was done by studying the full text, title, and methodology. The data were extracted by searching the terms apicectomy, lesion size, results and observation after 12 months, and method and the material used for the regeneration.

Cochrane risk of bias tool was used to assess the risk of bias for the randomized controlled trials, done by the reviewers that have fields on random sequence generations, blinding of reviewers and the patients, clinicians, blinding of outcome appraisers, unfinished outcome data, and reporting selectively. They were classified as three risks of high, moderate, and low.

The outcome was measured as the clinical and radiographic observation. In the statistical analysis, outcomes of interest were considered as success and failure. These were based on the radiographic and the clinical outputs. Success is described by the absence of clinical symptoms along with the presence of complete or incomplete radiographic healing. Failure is described by the presence of any clinical symptoms along with the presence of unclear radiographic healing.

Review Manager (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014. was used for the statistical analysis. The results were shown by the Forest plot that was used to assess the data from the comparable studies with the same procedures. Relative risk with 95% confidence intervals for dichotomous data was applied for the meta-analysis. Heterogeneity of the included studies was assessed using the I2 for each pooled estimate. P < 0.10 was considered significant. Publication bias was assessed by the funnel plots. The reported efficacy was compared with a control group and P < 0.05 was considered significant.

RESULTS

In the present systemic review, a total of 1561 articles were considered after the application of the inclusion and exclusion criteria. There were 1550 articles that were excluded as they were <1 year follow-up studies, retrospective studies without the specification of the regenerative material used in the study, animal trials, and experimental design. For the final consideration of the study, 11 of the articles were considered for the meta-analysis.[814151617181920212223] Figure 1 describes the selection of the articles.

Figure 1

Flow chart describing the selection of the articles

Features of the included articles

Tables 1 and 2 describe the characters of the study. In these eleven studies, a total of 263 patients were enrolled for the regenerative procedure, the controls were 196 patients. In some studies, there were comparisons of more than one regeneration material and their comparison with the control group. In the meta-analysis, various case groups were combined to do the single pairwise comparison with that of the nonintervention groups. In the subcategory analysis, statistics from the corresponding pair of case group was compared to the nonintervention groups. Table 1 depicts the type of the regenerative materials and their combination. Blinding of the examiners was not mentioned in 6 studies.

Table 1

Comparison of the included studies

Study ID	Mean age (y) [age range]	Lesion size; lesion type	Intervention group (IG)				Control group (CG)
			Regenerative materials	Cases	Success	Failure	Cases	Success	Failure
Pecora et al. (1995)	[27-50]	diameter ≥10 mm; through-and-through	e-PTFE membrane1	10	10	0	10	10	0
Tobon et al. (2002)	39.2 [14-74]	0.04-506 mm2 (radiographic)	e-PTFE membrane2	9	7	2	9	8	1
			synthetic bioactive graft3 + e-PTFE membrane2	8	8	0
Pecora et al. (2001)	48 [30-60]	diameter ≥ 10 mm; through-and-through	calcium sulphate graft	10	9	1	10	8	2
Taschieri et al. (2007)	female: 36 male: 43	diameter ≥10 mm; through-and-through or 4-wall	bovine-derived hydroxyapatite4 + collagen membrane5	17	16	1	24	22	2
Taschieri et al. (2008a)	female: 32 male: 47	diameter ≥10 mm; through-and-through	bovine-derived hydroxyapatite4 + collagen membrane5	17	15	2	14	8	6
Panel et al. (2011)	[17-58]	diameter: 6-21 mm (mean ± SD: IG: 14.77 ± 4.62 mm CG: 13.31 ± 5.51 mm)	bovine-derived hydroxyapatite4 + collagen membrane5	22	21	1	21	19	2
Chen & Shen (2016)	36	diameter ≥ 10 mm; through-and-though and others	bovine-derived hydroxyapatite4 + collagen membrane5	42	40	2	38	31	7
Wang el al. (2017)	60.02	25-640 mm2 (radiographic)	bovine-derived hydroxyapatite4 + collagen membrane5	17	15	2	15	11	4
Parmar et al. (2019)	IC: 26.27 CG: 26.87	diameter ≥ 10 mm; through-and-through	collagen membrane6	15	15	0	15	14	1
Dominiak et al. (2009)’	37.5 [9-60]	mean dimensions: width 8.38 × height 9 × depth 8.40 mm3	collagen membrane5	26	21	5	25	16	9
			bovine-derived hydroxyapatite4	30	25	5
			bovine-derived hydroxyapatite4 + PRP	25	23	2
Dhiman et al. (2015)	IG: 27.93 CG: 25.67	apicomarginal (confined to buccal aspect of the root)	PRF	15	13	2	15	12	3

1: Gore-Tex (WL Gore & Associates, Inc., Flagstaff, AZ, USA); 2: Gore-Tex Augmentation Gt4 submerged configuration (WL Gore & Associates, Inc., Flagstaff, AZ, USA); 3: OsteoGen (Impladent, Ltd., Holliswood, NY. USA); 4: Bio-Oss (Geistlich Pharma AG, Wolhusen, Switzerland); 5: Bio-Gide (Geistlich Pharma AG, Wolhusen, Switzerland); 6: Healiguide (Advanced Biotech. Chennai, India); 7: We extracted data from the ’bovine-derived hydroxyapatite + PRP’ group and ’bovine-derived hydroxyapatite’ group for the APC subgroup analysis, and the ’bovine-derived hydroxyapatite’ group served as the control group.

Table 2

The features of the studies considered for the meta-analysis

Features of the included studies	Number of studies
Total number of patients	459
Cases	263
Control	196
Collagen	2
Bovine-derived hydroxyapatite	1
Collagen + bovine-derived hydroxyapatite	5
E-ptfe	2
E-ptfe + hydroxyapatite	1
Calcium sulfate	1
APC-PRP	1
PRF	1

APC: Autologous platelet concentrate, PRP: Platelet-rich plasma, PRF: Platelet-rich fibrin, E-ptfe: Expanded polytetrafluoroethylene

To check the bias, six domains were selected. They are missing outcome data, randomization, selection of the reported results, deviation from intention, measurement of the outcome, and overall. In 2 studies, a lower bias was found. For the other studies, a moderate bias was found. In the included studies, the randomization was poorly described. The randomization was not explained in the 8 studies. Outcome was not thoroughly explained/judged in 6 studies. Only three studies completely explained all the three dominions. The calculation of risk of bias is revealed in Figure 2.

Figure 2

Risk-of-bias

Observations were made from this meta-analysis.

No heterogeneity was seen in the articles considered for the study. The units of the outcome were kept uniform. A statistically significant difference was seen in the case group than the control group with respect to the final outcome. For the comparison of the various materials, no statistically significant difference was seen when the APCs, collagen, and e-PTFE membranes were applied in the regenerative procedures Figure 3.

Figure 3

Failure rates analysis shown in the Forest plot. (a) e-ptfe membrane, (b) collagen membrane, (c) collagen membrane with hydroxyapetite, (d) APCs

However, their application enhanced the outcome than in the control groups. However when they were combined, there was observed significant better outcome. The funnel plot is shown in [Figure 4] that shows the publication bias.

Figure 4

Funnel plot

DISCUSSION

In clinical practice for the better clinical outcome, regenerative methods for the endodontic surgery are applied. In these regenerative methods, various materials have been used. However, there have been insufficient data that prove the efficiency of these materials.

From our meta-analysis, it was seen that the application of the various regenerative methods helps in a better outcome than those without the regenerative methods. No statistically significant difference was seen when the APCs, collagen, and e-PTFE membranes were applied in the regenerative procedures. However, their application enhanced the outcome than in the control groups. But when they were combined, there was observed significant better outcome.

It was also observed in the present study that the age ranged from 10 to 70 years. Equal gender distribution was seen. The teeth from all the four quadrants were included. Hence, the observations of the present review can be applied to the general population. The materials used are collagen and e-PTFE membranes, bone grafts, and APCs.

e-PTFE membranes is one the first materials that is biocompatible used in the endodontic regenerative procedures for the apicectomy.[23] The meta-analysis for the 2 studies included the e-PTFE membranes: Pecora[23] and Tobon et al.[14] However, the study output was contradictory to each other. This membrane however is prone to lodging the bacteria that may hamper the outcome in the regenerative procedures for the apicectomy. The recently developed high-density PTFE membrane may overcome this problem.

With respect to the collagen membrane, the observations of our study are in accordance with the previous studies. In our study, the combination of the collagen with the bovine material had better results than when used alone.[1723] However, the resorption of the material is slow. This material is easily accepted and does not elicit any host response. This precludes the necessity of the second intervention.[1924] To overcome the defects of the collagen alone, the bovine-derived hydroxyapatite is used in the combination. They are Bio-GideTM and Bio-OssTM. Bio-OssTM is treated by chemical and heat treatments and osteogenic capacity is lost. Hydroxyapatite is present in the io-OssTM that has a porous design. It has osteoconductivity and can act as a framework to permit the inflow of host osteogenic cells. Also it is biocompatible. Bio-OssTM resorbs slowly and incorporated in the osteogenesis. In the 5 trials from our study where Bio-GideTM+Bio-OssTM were applied, subcategory investigation depicted a significant improvement in the cases.

From the older studies, the size of the periapical lesion was also considered a prognostic factor. Delayed healing is seen for the apical lesions >5 mm in diameter. Five trials in our study included cases who had moderate to large apical lesions. We observed in our study that the combination of Bio-GideTM+Bio-OssTM could lead to better results after apicectomy for these cases.

APCs have been increasingly used in the recent as innovative regenerative materials in apicectomy. They have growth factors such as vascular endothelial growth factor, platelet-derived growth factor, and TGF-β.[25] They are extensively used in periodontal surgery; however, their application in apicectomy and other endodontic surgeries is to be assessed. Form the three studies that included the APCs, the healing and the clinical/radiographic results were satisfactory. Yet, there is a little evidence supporting the application of the various APCs in the endodontic surgery. Much more clinical studies are warranted to better understand the outcome with these materials.

There were some limitations in our study. The size of the lesion for the apicectomy was not generalized. The sample size varied among the included studies. Also, the recent advanced materials were not considered in the present meta-analysis. Research analysis is to be done with the new materials included. Only 1 year follow-up was done but the outcome after the long term is unknown. Randomization and blinding were unclear in majority of the studies. However, the risk of bias was low based on the 6 criteria to measure the bias. The study was neglected only if a fifth of the outcome was missing.[24] The present systemic review gives evidence-centered results and discourses the advantages and the disadvantages of the normally applied regenerative methods and constituents and should hence may be helpful to the endodontists for proper planning.

CONCLUSIONS

Application of the regenerative procedures in the apicectomy by the various materials helps in the present better healing after the endodontic surgery as shown in our study. Combination of the materials is advocated for the improved outcome than application of the individual material. Larger premeditated randomized controlled trials are imperative to evaluate the advantages of the various regenerative materials for the surgeries in endodontics.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.