2. S44 Journal of Pharmacy and Bioallied Sciences ¦ Volume 13 ¦ Supplement 1 ¦ June 2021
Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis
barrier.[3]
Mineral trioxide aggregate (MTA) is used as
reparative material for perforations and also used in
pulp capping and pulpotomy procedures, apical barrier
for open apex, and retrograde filling.[4]
Several clinical
studies of role of MAT in apexification is present in
literature.[5,6]
MTA is a mixture of Portland cement and
bismuth oxide, dicalcium silicate, tricalcium silicate,
tricalcium aluminate, and tetracalcium aluminoferrite,
as well as other mineral oxides.[7]
The pH of 12.5 after
setting is almost the same as calcium hydroxide.[7]
MTA
is the first material that had allowed overgrowth of
cementum and promotes regeneration of periodontal
tissues.[8]
Nevertheless, MTA had some disadvantages like
discoloration of the tooth and it weakened dentine walls
like calcium hydroxide.[9]
Recently, newer bioceramic
materials such as calcium‑enriched cement, Biodentine,
and EndoSequence Root Repair Material (ERRM) have
been marketed for various other endodontic procedures.[10]
ERRM contains calcium silicates, tantalum oxide, calcium
phosphate monobasic, and little amount of filler agents.
The nanosphere particles present in the cement pass
through the dentin tubules and react with moisture present
in dentin. ERRM has a bioactive nature which simulates
tissue fluid and results in the precipitation of apatite
crystals.[11]
This systematic review is done to compare
the effectiveness of MTA and Endosequence bioceramic
root repair material (BCRRM) and calcium hydroxide in
clinical success of apexification of immature permanent
teeth, thus solving the problem for a clinician in choosing
the material for apexification is the main objective of the
present study.
Materials and Methods
PICO: Population, Intervention, Comparison, Outcome
is described in Table 1.
Search module for identification of studies
A detailed search of all databases were done for doing
this systematic review. The computer database list for
reviewing the article is listed in Table 2.
Strategy of publication research
An electronic search was performed with keywords
and filter in database as listed in Table 2. Comparative
studies of apexification of necrotic immature permanent
teeth that met the inclusion criteria were evaluated. The
reference list of relevant articles was also searched and
evaluated.
Inclusion criteria and exclusion criteria for the review
are listed in Table 3.
Data extraction and characteristics of the study
for review
The following information/data were extracted from
shortlisted studies: author’s name, year of publication,
Table 3: Inclusion and exclusion criteria
Inclusion criteria Exclusion criteria
Conducted clinical trials on patients with permanent immature
teeth for which apexification was indicated
Review articles
Randomized controlled trials, prospective and retrospective
studies, and case series
In vitro studies
Compared calcium hydroxide versus MTA versus endosequence Nonhuman studies, letters, comments
Reported quantitative clinical or radiographic outcomes Editorials, case reports, proceedings, and personal communications
were excluded
MTA: Mineral trioxide aggregate
Table 1: PICO question
P patient, population, or problem Immature necrotic permanent teeth
I intervention, prognostic factor, or exposure Biomaterials for apexification
C comparison or intervention (if appropriate) Calcium hydroxide, mineral trioxide aggregate, endosequence
O outcome you would like to measure or achieve Clinical success with no clinical signs and symptoms
radiographic apical closure (evaluating root length and thickness)
Table 2: Search strategy
Electronic
databases
Google Scholar, PubMed, Scopus, Cochrane, Research Gate, Wiley online library, and other hand searched journals:
Journal of endodontics, international endodontic journal, journal of conservative dentistry
Keywords Apexification, mineral trioxide aggregate, calcium hydroxide, bioceramic, endosequence, randomized controlled trials
Filters English language, humans, from source till November 2020
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Journal of Pharmacy and Bioallied Sciences ¦ Volume 13 ¦ Supplement 1 ¦ June 2021
Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis
design of the study, number of teeth studied, age and
sex of the participants, clinical success and radiographic
success, time taken for apical barrier formation, and
follow‑up details evaluated.
Study selection
Of the 410 studies that were identified, 150 articles
were selected after title/abstract reading. After full‑text
reading and based on inclusion and exclusion criteria, 9
studies were finalized for systematic review. A flowchart
for selecting the articles for review was generated with
PRISMA guidelines listed in Figure 1.
Study characteristics
El Meligy and Avery[12]
aimed to compare the clinical
and radiographic success by conducting a study on 15
children with minimum 2 necrotic immature permanent
teeth. Apexification was done after root canal treatment
protocol with calcium hydroxide or MTA. The evaluation
was carried out every 3, 6, and 12 months. Only two teeth
among 15 teeth that were treated with calcium hydroxide
showed clinical symptoms such as tenderness on
percussion and persistent periradicular inflammation. None
of the teeth that were treated with MTA showed failure
on every 3‑, 6‑, and 12‑month follow‑up visit. Pradhan
et al.[13]
conducted this study to compare the efficacy
and the time taken for apical biologic calcific barrier
formation and resolution of periapical radiolucencies on
20 teeth with unformed apices. Teeth were stratified based
on radiolucency in the periapical region. After routine
root canal treatment, Group I was packed with MTA
and obturated with gutta percha. In Group II, calcium
hydroxide dressing was done till the apical stop was
achieved and then obturated. The result showed that it
took 3 ± 2.9 months for apical barrier formation in MTA
groups and 7 ± 2.5 months in calcium hydroxide groups.
There was no significant difference in healing time of
periapical radiolucencies. Simon et al.[14]
conducted a
prospective study (randomized) from June 2001 to June
2005 on 57 immature permanent teeth on 50 patients.
The same operator treated all teeth in one appointment.
The operator placed gray MTA in cases 1–11 and white
MTA in cases 11–57. The remaining part of the canal was
obturated with warm vertical compaction of gutta percha.
Two examiners assessed the pretreatment, posttreatment,
and review radiographs using magnifiers taken every 6
months, 12 months, and every year thereafter. Eighty‑one
percent of cases showed a decrease in size of the
periapical lesion. Apical foramen closure was 88%. Bonte
et al.[16]
conducted a randomized clinical trial on children
with necrotic permanent teeth with calcium hydroxide or
MTA apexification and evaluated after 6 and 12 months.
Fifty percent of the teeth treated with calcium hydroxide
group showed mineralized barrier and 82% in the MTA
apexification. However, four teeth treated with calcium
hydroxide showed radicular fractures and 82% in the MTA
group. Lee et al.[17]
conducted apexification study on 40
necrotic immature open apex incisors and evenly divided
them into diffrent groups (calcium hydroxide and MTA
with hand and ultrasonic filing). Two conclusions derived,
that root length elongation was better in teeth treated with
calcium hydroxide and short time need for apical barrier
in MTA apexification with ultrasonic filing. A comparative
study by Damle et al.[18]
compared and evaluated the
apexification potential of calcium hydroxide and MTA in
22 traumatized young permanent anterior teeth among the
age group of 10–11 years, and the study revealed MTA
showing superior clinical outcome compared to calcium
hydroxide with MTA showing 90.9% success and calcium
Figure 1: PRISMA guidelines for study selection
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4. S46 Journal of Pharmacy and Bioallied Sciences ¦ Volume 13 ¦ Supplement 1 ¦ June 2021
Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis
hydroxide showed only 81.8% success rate. Sarnowski[19]
had done a thesis on open apex treated with bioceramic
apical barrier and studied its success and survival rates at
Virginia Commonwealth University in 2019. Patient record
taken from resident cases completed at the university
from January 1, 2010 to May 31, 2018. A total of 119
teeth were identified that were treated for open apex with
BCRRM. Only 36 teeth were under follow‑up in which
72% were considered healed and 2% were healing which
shows bioceramic apical had showed a good clinical
outcome. Study by Barakat and Fethi.[20]
The study was
composed of sixty teeth from 54 children with age ranged
from 7 to 10 years. Children were divided in to two equal
groups: 1‑Group A: teeth were received apexification with
MTA 2‑Group B: teeth were received apexification with
bioceramic root canal sealer. All patients were followed
clinically and radiographically immediate postoperatively,
3 and 6 months [Table 4].
Results
The success rate in both bioceramic and MTA was
93.3% and 90%, respectively, with no statistically
significant difference. Conclusions: both MTA and
bioceramic sealer show good results.
Discussion
The purpose of this systematic review was to determine
whether Endosequence BCRRM, MTA or calcium
hydroxide provides better clinical and radiologic
outcomes for the apexification of immature permanent
teeth. These three materials have their unique
advantages and drawbacks and also there is no literature
evidence comparing these three materials. There are
few systematic reviews and meta‑analysis comparing
calcium hydroxide and MTA only. Three systematic
reviews and meta‑analysis by Lin et al.,[21]
Chala et al.[22]
and Nicoloso et al.,[23]
compared calcium hydroxide and
MTA for apexification of immature permanent teeth,
studies reviewed and concluded that MTA showed better
healing in terms of clinical and radiographic success,
and the apical barrier was formed within a short period
of time compared to calcium hydroxide. Although MTA
proved to be a promising material for apexification, it
carries some disadvantages such as discoloration and
weakening of dentine walls.[9]
Duraivel[24]
in 2014,
described a series of cases where apexification was
performed in single visit in three different patients using
ERRM, MTA, and Biodentin. All the patients were
recalled after 1 month for follow‑up and it proved that
ERRM can be used as an alternative to MTA. Although
ERRM is considered as a substitute for MTA, only
Table 4: Studies investigated for systematic review
Study (years) Study type Sample
size
Intervention Age
(years)
Clinical
success (%)
Radiographic
success (%)
Time required for apical
barrier formation
El Meligy and
Avery[12]
(2006)
RCT 15 MTA NR 100 100 NR (follow-up - 3, 6, and
9 months)
RCT 15 Calcium hydroxide 6-12 87 87 NR (follow-up - 3, 6, and
9 months)
Pradhan et al.[13]
(2006)
Clinical
comparative study
10 MTA NR 100 NR 3±2.9 months
10 Calcium hydroxide NR 100 NR 7±2.5 months
Simon et al.[14]
(2007)
Prospective study 57 MTA 18 81 88 Follow-up - 12 months
Neveu et al.[15]
(2011)
RCT 15
15
MTA
Calcium hydroxide
6-18 NR NRV Follow-up - 3, 6, and 12
months
Bonte et al.[16]
(2015)
In vivo clinical
trial
17
16
MTA
Calcium hydroxide
10.2
10.9
83.4
75
76.5
50
NR
Lee et al.[17]
(2015)
RCT 40 MTA and CaOH
with ultrasonic and
hand filing
6.5-10 100 100 5.4±1.1 weeks
Damle et al.[18]
(2016)
RCT 11
11
MTA
Calcium hydroxide
10±1.41
10.8±1.32
100
93.3
90.9
81.8
4.9
5.3
Sarnowski[19]
(2019)
Published
dissertation
36 Bioceramic (proroot
MTA, endosequence
root repair material)
17 92 92 Follow-up up to 2 years
Barakat and
Fethi[20]
(2020)
In vivo clinical
trial
30
30
MTA
Bioceramic root
canal sealer
9±1.2
9.5±1.08
100
100
90
93.3
3 months
MTA: Mineral trioxide aggregate, NR: Not reported, RCT: Randomized clinical trials
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Journal of Pharmacy and Bioallied Sciences ¦ Volume 13 ¦ Supplement 1 ¦ June 2021
Shaik, et al.: Apexification of immature permanent teeth: Systematic review and meta analysis
very few articles compared Endosequence and MTA
for apexification of nonvital immature permanent teeth.
Further clinical trials need to be conducted to compare
it with other apexification materials. Few stidues were
baised due to lack of proper random sequencing,
improper employed blinding and no long term follow
up. Therefore, more studies are required to compare all
apexification materials with an appropriate allocation
concealment, randomization technique, and blinding.
Conclusion
Based on the above studies evaluated, all the three
materials had almost similar clinical success rates,
radiographic success rates, and apical barrier formation
rates. However, MTA and Endosequence BCRRM were
associated with a significantly shorter time to achieve
apical barrier formation than the calcium hydroxide.
Although MTA and ERRM showed good results, there are
only limited studies to evaluate MTA and ERRM. Hence,
more comparative studies are required to prove the best
material for apexification of immature permanent teeth.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Chueh LH, Ho YC, Kuo TC, Lai WH, Chen YH, Chiang CP.
Regenerative endodontic treatment for necrotic immature
permanent teeth. J Endod 2009;35:160‑4.
2. Huang GT, Sonoyama W, Liu Y, Liu H, Wang S, Shi S. The
hidden treasure in apical papilla: The potential role in pulp/dentin
regeneration and bioroot engineering J Endod 2008;34:645‑51.
3. Sheehy EC, Roberts GJ. Use of calcium hydroxide for apical
barrier formation and healing in non‑vital immature permanent
teeth: A review. Br Dent J 1997;183:241‑6.
4. Anthonappa RP, King NM, Martens LC. Is there sufficient
evidence to support the long‑term efficacy of mineral trioxide
aggregate (MTA) for endodontic therapy in primary teeth? Int
Endod J 2013;46:198‑204.
5. Damle SG, Bhattal H, Loomba A. Apexification of anterior teeth:
A comparative evaluation of mineral trioxide aggregate and
calcium hydroxide paste. J Clin Pediatr Dent 2012;36:263‑8.
6. Park M, Ahn BD. Immature permanent teeth with apical
periodontitis and abscess treated by regenerative endodontic
treatment using calcium hydroxide and MTA: A report of two
cases. Pediatr Dent 2014;36:107‑10.
7. Sarkar NK, Caicedo R, Ritwik P, Moiseyeva R, Kawashima I.
Physicochemical basis of the biologic properties of mineral
trioxide aggregate. J Endod 2005;31:97‑100.
8. Parirokh M, Torabinejad M. Mineral trioxide aggregate:
A comprehensive literature reviewe Part III: Clinical applications,
drawbacks, and mechanism of action. J Endod 2010;36:400‑13.
9. Krastl G, Allgayer N, Lenherr P, Filippi A, Taneja P, Weiger R.
Tooth discoloration induced by endodontic materials: A literature
review. Dent Traumatol 2013;29:2‑7.
10. Utneja S, Nawal RR, Talwar S, Verma M. Current perspectives
of bio‑ceramic technology in endodontics: Calcium enriched
mixture cement – Review of its composition, properties and
applications. Restor Dent Endod 2015;40:1‑13.
11. Damas BA, Wheater MA, Bringas JS, Hoen MM. Cytotoxicity
comparison of mineral trioxide aggregates and endoSequence
bioceramic root repair materials. J Endod 2011;37:372‑5.
12. El Meligy OA, Avery DR. Comparison of apexification with
mineral trioxide aggregate and calcium hydroxide. J Pediatr Dent
2006;28:248‑53.
13. Pradhan DP, Chawla HS, Gauba K, Goyal A. Comparative
evaluation of endodontic management of teeth with unformed
apices with mineral trioxide aggregate and calcium hydroxide.
J Dent Child (Chic) 2006;73:79‑85.
14. Simon S, Rilliard F, Berdal A, Machtou P. The use of mineral
trioxide aggregate in one‑visit apexification treatment:
A prospective study. Int Endod J 2007;40:186‑97.
15. Neveu B, Bonte E, Baune B, Serreau S, Aissal F, Quinquis L,
et al. Mineral trioxyde aggregate versus calcium hydroxide in
apexification of non vital immature teeth: Study protocol for a
randomized controlled trial. Trials 2011;12:174.
16. Bonte E, Beslot A, Boukpessi T, Lasfargues JJ. MTA versus
Ca(OH)2
in apexification of non‑vital immature permanent
teeth: A randomized clinical trial comparison. Clin Oral Investig
2015;19:1381‑8.
17. Lee LW, Hsieh SC, Lin YH, Huang CF, Hsiao SH, Hung WC.
Comparison of clinical outcomes for 40 necrotic immature
permanent incisors treated with calcium hydroxide or mineral
trioxide aggregate apexification/apexogenesis. J Formos Med
Assoc 2015;114:139‑46.
18. Damle SG, Bhattal H, Damle D, Dhindsa A, Loomba A,
Singla S. Clinical and radiographic assessment of mineral
trioxide aggregate and calcium hydroxide as apexification agents
in traumatized young permanent anterior teeth: A comparative
study. Dent Res J 2016;13:284‑91.
19. Sarnowski A. Management of Open Apex Using a Bioceramic
apical Barrier‑its Success and Survival Rates at Virginia
Commonwealth University. VCU: Virginia Common Wealth
University; 2019.
20. Barakat IF, Fethi A. Clinical and radiographical evaluation
of bioceramic root canal sealer and MTA in apexification of
immature permanent teeth. Egypt Dent J 2020;66:2057‑63.
21. Lin JC, Xuan Lu JX, Zeng Q, Zhao W, Li WQ, Ling JQ.
Comparison of mineral trioxide aggregate and calcium hydroxide
for apexification of immature permanent teeth: A systematic
review and meta‑analysis. J Formos Med Assoc 2016;115:523‑30.
22. Chala S, Abouqal R, Rida S. Apexification of immature teeth
with calcium hydroxide or mineral trioxide aggregate: Systematic
review and meta‑analysis. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2011;112:e36‑42.
23. Nicoloso GF, Pötter IG, Rocha RO, Montagner F, Casagrande L.
A comparative evaluation of endodontic treatments for immature
necrotic permanent teeth based on clinical and radiographic
outcomes: A systematic review and meta‑analysis. Int J Paediatr
Dent 2017;27:217‑27.
24. Duraivel D. Management of non vital teeth with open apex using
endosequence root repair material, mineral trioxide aggregate
and biodentin – A case series. J Conserv Dent 2014;17:340‑3.
[Downloaded free from http://www.jpbsonline.org on Sunday, June 6, 2021, IP: 175.101.146.64]