77th Publication- JPBS- 2nd Name.pdf

S927
© 2021 Journal of Pharmacy and Bioallied Sciences | Published by Wolters Kluwer - Medknow
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.
Keywords: Apicoectomy, bone regeneration methods, meta‑analysis, root end
cutting
Various Assisted Bone Regeneration in Apicectomy Defects Systematic
Review and Meta Analysis
Ananad Sumangali1
, Rahul V. C. Tiwari2
, Jeevana Kollipara3
, Mubashir Baig Mirza4
, Rajwinder Singh Brar5
,
Akshay M. Dhewale6
Access this article online
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Website: www.jpbsonline.org
DOI: 10.4103/jpbs.jpbs_375_21
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
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
1
Department of Endodontics,
Sebha Dental College,
University of Sebha,
Sebha, Libya, North
Africa, 2
Department
of OMFS, Narsinbhai
Patel Dental College and
Hospital, Sankalchand
Patel University, Visnagar,
Gujarat, India, 3
BDS,
Government Dental College,
Hyderabad, Telangana, India,
4
Department of Conservative
Dental Science, College of
Dentistry, Prince Sattam
bin Abdulaziz University,
Al Kharj, Saudi Arabia,
5
Department of Orthodontics,
Rayat Bahra Dental College,
SAS Nagar, Punjab, India,
6
Department of Conservative
Dentistry and Endodontics,
VYWS Dental College
and Hospital, Amravati,
Maharashtra, India
Abstract
Address for correspondence: Dr. Ananad Sumangali,
Endodontist, Associate Professor, Sebha Dental College,
University of Sebha, Sebha, Libya.
E‑mail: sumiadr@yahoo.in
This is an open access article distributed under the terms of the Creative Commons
Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak,
and build upon the work non‑commercially, as long as the author is credited and the new
creations are licensed under the identical terms.
For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com
How to cite this article: SumangaliA,TiwariRV,KolliparaJ,MirzaMB,BrarRS,
Dhewale AM. Various assisted bone regeneration in apicectomy defects
systematic review and meta analysis. J Pharm Bioall Sci 2021;13:S927-32.
Review Article
Submitted : 08‑May‑2021
Revised : 15-May-2021
Accepted : 21‑May‑2021
Published : 10-Nov-2021
[Downloaded free from http://www.jpbsonline.org on Wednesday, November 10, 2021, IP: 49.204.225.73]

S928 Journal of Pharmacy and Bioallied Sciences ¦ Volume 13 ¦ Supplement 2 ¦ August 2021
Sumangali, et al.: Bone regeneration in apicectomy defects
to the previous tissue.[2‑5]
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.[5,6]
However, there are various studies that report
varying degree of the success using the regenerative
methods.[7‑13]
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
1. Randomized Controlled trial
2. Root end surgery for persistent periapical pathology
3. 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.[8,14‑23]
Figure 1 describes
the selection of the articles.

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Journal of Pharmacy and Bioallied Sciences ¦ Volume 13 ¦ Supplement 2 ¦ August 2021
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.
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 Figures 2.
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.
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.
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.
Figure 1: Flow chart describing the selection of the articles
Table 1: Comparison of the included studies
Figure 2: Risk‑of‑bias

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
Figure 4: Funnel plot
Figure 3: Failure rates analysis shown in the Forest plot. (a) e-ptfe membrane, (b) collagen membrane, (c) collagen membrane with hydroxyapetite, (d)APCs
d
c
b
a

S931
Journal of Pharmacy and Bioallied Sciences ¦ Volume 13 ¦ Supplement 2 ¦ August 2021
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.[17,23]
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.[1,9,24]
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.
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