Comparison of MTA and Ca(OH) 2 for the apexification of necrotic immature permanent teeth An Evidence Based Report

Comparison of MTA and Ca(OH) 2 for the apexification of necrotic immature permanent teeth An Evidence Based Report Allison Clark, Anthony Pino, Danielle Attoe, Fatemeh Farzin, Keith Li, Malisa Gambacorta DEN 207Y1 Community Dentistry, DDS II University of Toronto, Faculty of Dentistry, Toronto, Canada

ABSTRACT As new treatment options become available, it is of utmost importance that dental professionals research these options in an evidence based manner to determine the most appropriate treatment approach. This research was conducted in an attempt to find the best treatment for necrotic immature permanent teeth, specifically mineral trioxide aggregate (MTA) compared to the standard treatment, calcium hydroxide (Ca(OH) 2 ). A systematic search of scientific literature was conducted in order to identify, select, and critically appraise the relevant literature. To formulate a list of keywords for the systematic search, a preliminary non systematic search was conducted. Following the selection of key search words, the PubMed literature database was utilized. Inclusion criteria selected for studies in English, and only those that had been completed on humans in vivo. The systematic search and critical appraisal of the relevant literature resulted in one article by El Meligy & Avery that compared MTA and Ca(OH) 2 apexification in a randomized split mouth controlled clinical trial with blinding. The results of this study determined that the clinical and radiographic success rate for MTA was 100% and for Ca(OH) 2 was 87%. MTA and Ca(OH) 2 each have advantages and disadvantages, this report identifies these differences, but determines that further randomized controlled studies are required before it can be stated that either option is superior to the other.

INTRODUCTION Approximately 30% of children will experience trauma to their young permanent teeth. 1 Traumatic injuries to immature permanent teeth may eventually result in pulpal necrosis and the arrest of root development. 2 Apexification is the treatment of choice for immature necrotic teeth. 1 In such non vital teeth, the root has not yet completely developed and thus it is comprised of thin dentinal walls which are prone to fracture during normal masticatory forces. 3 Furthermore, the root apex of a non vital immature tooth is relatively large and open to the neighbouring environment. 3 Due to the lack of apical closure, an intact seal of the root canal to retain the root canal filling material is not possible. 4 As a result, when such a tooth requires endodontic treatment, it presents itself as a lengthy and technique sensitive procedure. 3 In premature necrotic teeth, the open root apex is closed by an apexification technique prior to performing root canal therapy. Apexification permits a barrier to be formed at the root apex, allowing for proper condensation and retention of the root canal filling. 5 The standard treatment is currently the apexification procedure involving the use of calcium hydroxide (Ca(OH) 2 ). This treatment option has been fairly successful, yet it poses some problems that could be addressed as new materials emerge and as research in this area continues. Albeit popular and the standard treatment option, Ca(OH) 2 may not be the most ideal material for apexification due to the variability in treatment time and difficulty in patient follow up. 6 Apexification performed with Ca(OH) 2 is quite time consuming, requiring about 7 to 8 months on average for apical barrier formation. 2 Also, the time required to achieve apical closure is not reliable and

can range anywhere from 3 to 21 months 4, which undoubtedly can be frustrating for the patients who have to attend multiple appointments over such a prolonged treatment time. Due to the lengthy treatment time, there is a risk of the patient not returning for follow up appointments, which in turn increases the likelihood of failure. 2 Multiple appointments results in more time lost from work, costing the patients parents the cost of additional treatment as well as time lost from work. Another concern is that the tooth remains prone to fracture until the treatment is successful. Dr. Malkhassian, an endodontist at the University of Toronto, suggests that the longer the tooth has been necrotic, the less likely that Ca(OH) 2 will lead to apical closure. Such issues with Ca(OH) 2 are the reason that new materials may replace Ca(OH) 2 as the standard treatment for apexification in the future. Recently, mineral trioxide aggregate (MTA) has received a great deal of interest among dental clinicians. 1 In 1998, the US Food and Drug Administration approved MTA for use in endodontic procedures. 6 MTA allows for an immediate apical barrier to be formed and thus immediate obturation of the root canal system. 2 MTA may therefore solve some of the problems currently experienced in apexification using Ca(OH) 2. Aside from apexification, two other techniques have just recently evolved as treatment options for immature necrotic teeth: revitalization and tissue engineering. 7 These two treatment modalities were not included in this paper because more research into these areas is needed. As new treatment options become available, it is of utmost importance to research what options are the best in an evidence based manner in order to strive to give patients the best possible treatment. The purpose of this paper is to

compare apexification techniques using the traditional Ca(OH) 2 method and the more recent and promising MTA. METHODS A systematic search of scientific literature was conducted to determine the best treatment option for a necrotic immature permanent tooth, specifically comparing apexification of MTA versus Ca(OH) 2. A systematic method was used in order to identify, select, and critically appraise the relevant literature in order to answer a formulated PICOC (Population, Intervention, Control, Outcome, Critical Appraisal) question in an evidence based manner. The PICOC used was: permanent immature necrotic teeth (population), MTA (intervention), Ca(OH) 2 (control), clinical and radiographic success (outcome), and randomized controlled trial (critical appraisal). To compile a list of keywords for the PICOC question and systematic search, a preliminary non systematic search was conducted, including a MeSH term search on PubMed. The keywords (Fig. 1) and inclusion criteria were then used to search for relevant literature using PubMed. The inclusion criteria for the PubMed search were human and English. The PubMed search produced 162 results. The titles were read by the authors as a group, and 31 articles deemed potentially relevant to the topic were kept for further analysis. The abstracts of the 31 remaining articles were then assessed by the group and 6 articles were judged as relevant to the topic according to inclusion criteria. These

inclusion criteria were: in vivo, minimum of 15 cases, studied either Ca(OH) 2 or MTA, not a case report, and not a review article. Each of the 6 articles were read and critically appraised by at least two group members independently, who compared their appraisals and came to an agreement afterward. The critical appraisals were completed using a detailed checklist to assess evidence of efficacy of therapy or prevention (Fig. 2). Of the 6 articles critically appraised, only one article compared MTA and Ca(OH) 2 (Fig. 3). The other 5 articles were one sided, investigating only one material, and therefore did not meet all of the inclusion criteria. However, these additional articles were included in the discussion as they were able to demonstrate the efficacy of each individual treatment. Evidence was extracted from all 6 articles and summarized (Tables 1 and 2). Fig. 1. Keywords and search strategy entered into PubMed to search for relevant literature Population: Intervention: (necrotic OR non vital OR nonvital OR necrosis OR necroses OR pulpless) AND (premature OR immature OR underdeveloped OR under developed OR undeveloped) AND (MTA OR mineral trioxide aggregat* OR portland cement) OR Control: (Calcium hydroxide OR Ca(OH)2 OR CaOH2) AND (Apexification* OR apexogenesis OR apexogeneses)

Fig. 2. Checklist to Assess Evidence of Efficacy of Therapy or Prevention 1. Was the study ethical? 2. Was a strong design used to assess efficacy? 3. Were outcomes (benefits and harms) validly and reliably measured? 4. Were interventions validly and reliably measured? 5. What were the results? Was the treatment effect large enough to be clinically important? Was the estimate of the treatment effect beyond chance and relatively precise? If the findings were no difference was the power of the study 80% or better 6. Are the results of the study valid? Was the assignment of patients to treatments randomised? Were all patients who entered the trial properly accounted for and attributed at its conclusion? i) Was loss to follow up less than 20% and balanced between test and controls ii) Were patients analysed in the groups to which they were randomised? Was the study of sufficient duration? Were patients, health workers, and study personnel blind to treatment? Were the groups similar at the start of the trial? Aside from the experimental intervention, were the groups treated equally? Was care received outside the study identified and controlled for 7. Will the results help in caring for your patients? Were all clinically important outcomes considered? Are the likely benefits of treatment worth the potential harms and costs? Adapted from: Fletcher, Fletcher and Wagner. Clinical epidemiology the essentials. 3rd ed. 996, and Sackett et al. Evidence based medicine: how to practice and teach EBM. 1997 Fig. 3. Search results flowchart Titles: 162 results Abstract: 31 articles Read through: 6 articles Accepted: 1 article

RESULTS The systematic search and critical appraisal of the literature resulted in one article that compared apexification results using either MTA or Ca(OH) 2 in a randomized split mouth controlled clinical trial with blinding (Fig. 4). This article provided the strongest evidence compared to the other five articles which used weaker study designs (Table 2). In this study, El Meligy and Avery compared the clinical and radiographic findings of each treatment option in its ability to close root apices in necrotic permanent teeth with immature (open) apices. 4 Since radiographs and clinical findings were used as opposed to histological evidence, some error in detecting a seal formation could have been possible. Evidence extracted from this article, including the critical appraisal, was summarized in Table 1. For their study, El Meligy and Avery selected 15 healthy and cooperative children ranging from 6 to 12 years old, who had at least 2 necrotic permanent teeth requiring apexification treatment. These children were selected from the Pediatric Dental Clinic at the Faculty of Dentistry, Alexandria University, Alexandria, Egypt, and they were invited for a 12 month treatment period. A total of 30 teeth were evenly divided into either the control group (Ca(OH) 2 apexification) or the experimental group (MTA apexification). Clinical and radiographic evaluations were conducted after 3, 6, and 12 months. 4 El Meligy and Avery found that the clinical and radiographic success rate for MTA was 100% and for Ca(OH) 2 was 87%. Both examiners in the study reported identical clinical success (no pain, no tenderness to percussion, no swelling or fistula) and radiographic success (normal periodontal ligament, no periapical radiolucency, no

external root resorption). 4 However, El Meligy and Avery stated that there was no statistically significant difference between the two apexification treatments, clinically or radiographically, according to the chi square test (chi square=2.14; P=0.16). They concluded that MTA could potentially be an appropriate substitute for Ca(OH) 2 in apexification treatment. 4 Fig. 4. Design of study by Meligy and Avery (2006) 4 30 immature necrotic permanent teeth from 15 children 2 randomly selected groups Split mouth trial 15 treated with Ca(OH) 2 15 treated with MTA Blinded examiners looked at clinical and radiographic success of treatment at 3, 6, and 12 months DISCUSSION Based on the results, the merits of using MTA instead of Ca(OH) 2 can be seen, mainly for its ability to achieve apical closure as successfully as Ca(OH) 2, but in less time 4,8 11. Calcium hydroxide has been deemed the standard treatment for apexification, but the duration of treatment is variable and can range from 3 to 21 months. 4 The diameter of the apical opening, the level of damage and necrosis of the tooth, and the

variable repositioning methods are some of the factors that may affect the duration of treatment. 4 During that time frame, the tooth is vulnerable to re infection from coronal leakage if the temporization technique fails. In addition, the root canal is still in the midst of apexification for this prolonged period of time, so it is weak and prone to fracture. 4 These disadvantages can be avoided by using MTA as it can be placed immediately after disinfection. MTA is an effective apical plug and demonstrates good adaptation at the margins of the root apices. Furthermore, MTA sets relatively fast, in approximately four hours, and is biocompatible at the root apex. 4 Due to its fast setting time, patient compliance is much less of a concern as there are fewer follow up appointments required compared to Ca(OH) 2. However, the sandy consistency of MTA makes it more difficult to work with compared to Ca(OH) 2 and it is much more expensive for the initial treatment. 4 A single 1 gram packet of MTA intended for one use costs approximately $300. 4 However, the overall cost may not be much more for MTA, considering that it may take a few treatments for Ca(OH) 2 to work, and more appointments can results in lost income due to missing work for those appointments. Based on the results of El Meligy and Avery, the success rates of MTA and Ca(OH) 2 had no statistically significant difference. 4 While they failed to achieve a statistically significant difference, the relative difference of 13% that they found could be clinically significant. From a statistical standpoint, it is widely known that very unimpressive P values can result from studies showing a strong treatment effect if there is a low sample size. Using a conventional power of 80%, a relative difference of 15%

between treatment options, we found that a sample size of 76 patients would be needed to achieve statistical significant. Therefore, if larger randomized controlled trials are performed in the future, MTA may show a significantly higher success rate than Ca(OH) 2. The study by El Meligy and Avery had little bias as the control and experimental groups were randomized and the observers were blinded to treatment when examining the results. 4 Clinical examination and radiographic observations were recorded, which generated thorough details of successful or non successful treatment. Clinical observation without the use of radiographs would not have been a sufficient examination as a patient may not experience pain, sensitivity or any other noticeable symptom following incomplete apexification. A radiographic exam enhances detection of apex formation following either treatment. The greatest weakness in this study was that too few subjects were used (only 15 samples in each group). 4 A larger sample size would have strengthened the results. According to the current research available, MTA and Ca(OH) 2 have similar success rates. 4,8 11 Thus, the decision to use either treatment depends on other factors, such as cost, ease of treatment, and patient compliance. If a patient opts for the Ca(OH) 2 treatment because it is less expensive, the patient should also keep in mind the intrinsic cost of time as treatment takes 3 to 21 months and the risk due to the inherent vulnerability of the tooth during that time. 4 In addition, if the treatment fails, the cost of re treatment will have to be paid again and the patient will need to spend considerably more time at the dentist office, potentially resulting in further expenses and lost wages.

Choosing MTA treatment will certainly cost more initially, however the treatment will be done within the first appointment and the failure rate after the first treatment is lower than with Ca(OH) 2. 4,8 11 Five studies were found during the systematic search (Table 2) that tested either MTA or Ca(OH) 2, but did not compare the two techniques. 8 12 All five studies showed that the individual treatments were highly successful. Interestingly and possibly raising suspicion of their findings, all of the papers studying Ca(OH) 2 claimed that it was 100% effective. 9 12 This was due to the fact that the clinicians continued treating the subjects until apical closure was achieved, and focussed on the duration of treatment as opposed to initial success. That being said, the major limitation of this systematic review of the literature is that it was limited to only one well performed study. 4 Additional resources and the results of other randomized controlled trials would have been largely advantageous. Contacting the author would have added more insight into the topic, however there were time constraints with the submission of this review. In addition, the research was limited to publications in the English language, and grey literature was not included as it was not part of the systematic search method while it may have provided further insight. In conclusion, additional research, especially randomized controlled trials with more subjects, comparing MTA and Ca(OH) 2 for apexification is recommended. MTA has several apparent advantages and has the potential to replace Ca(OH) 2. Dr. Calvin Torneck, an endodontist from the University of Toronto, suggested that MTA will only have a place in endodontic therapy if cheaper synthetic materials are made in the

future. He also stated that a synthetic MTA is currently being developed in Brazil. There are also other upcoming and exciting treatment options for the apical closure of a permanent necrotic immature tooth, such as the regeneration of the apex. Revascularization, which is the regeneration of the apex via blood clot stimulation 13 and stem cell regeneration, the regeneration of the apex using stem cells 14 are two new areas of research. Ca(OH) 2 has been the standard material for apexification for many years and has been shown to achieve success, while undoubtedly possessing multiple drawbacks. With the addition of MTA to the option list and apical regeneration being considered, the future for successful treatment of necrotic immature permanent teeth is promising. Continued research will certainly lead to faster and more reliable treatment options for patients with necrotic immature permanent teeth.

REFERENCES 1. Rafter M. Apexification: a review. Dent Traumatol. 2005;21:1 8. 2. 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(2):79 85. 3. Al Ansary MA, Day PF, Duggal MS, Brunton PA. Interventions for treating traumatized necrotic immature permanent anterior teeth: inducing a calcific barrier & root strengthening. Dent Traumatol. 2009;25(4):367 79. 4. El Meligy OA, Avery DR. Comparison of apexification with mineral trioxide aggregate and calcium hydroxide. Pediatr Dent. 2006;28(3):248 53. 5. Friedlander LT, Cullinan MP, Love RM. Dental stem cells and their potential role in apexogenesis and apexification. Int Endod J. 2009;42(11):955 62. 6. Schwartz RS, Mauger M, Clement DJ, Walker WA 3rd. Mineral trioxide aggregate: a new material for endodontics. J Am Dent Assoc. 1999;130(7):967 75. 7. Huang GT. Apexification: the beginning of its end. Int Endod J. 2009;42(10):855 66. 8. Sarris S, Tahmassebi JF, Duggal MS, Cross IA. A clinical evaluation of mineral trioxide aggregate for root end closure of non vital immature permanent incisors in children a pilot study. Dent Traumatol. 2008;24(1):79 85. 9. Dominguez Reyes A, Muñoz Muñoz L, Aznar Martín T. Study of calcium hydroxide apexification in 26 young permanent incisors. Dent Traumatol. 2005;21(3):141 5. 10. Finucane D, Kinirons MJ. Non vital immature permanent incisors: factors that may influence treatment outcome. Endod Dent Traumatol. 1999;15(6):273 7. 11. Walia T, Chawla HS, Gauba K. Management of wide open apices in non vital permanent teeth with Ca(OH)2 paste. J Clin Pediatr Dent. 2000;25(1):51 6. 12. Kinirons MJ, Srinivasan V, Welbury RR, Finucane D. A study in two centres of variations in the time of apical barrier detection and barrier position in nonvital immature permanent incisors. Int J Paediatr Dent. 2001;11(6):447 51. 13. Thibodeau B, Trope M. Pulp revascularization of a necrotic infected immature permanent tooth: case report and review of the literature. Pediatr Dent. 2007;29(1):47 50.

14. Friedlander LT, Cullinan MP, Love RM. Dental stem cells and their potential role in apexogenesis and apexification. Int Endod J. 2009;42(11):955 62.

Author, Date, Location Population Intervention (number studied) Control (number studied) Outcome Critical Appraisal Comments Conclusion, Strength of Evidence and Classification Number of Sessions Meligy & Avery 2006 Comparison of Apexification With Mineral Trioxide Aggregate and Calcium Hydroxide Alexandria, Egypt 15 children, each with 2 necrotic permanent teeth with immature apices (24 maxillary central incisors and 6 lateral incisors); age 6 12yrs MTA N=15 Ca(OH) 2 N=15 Ca(OH) 2 87% clinical and radiographic success MTA 100% clinical and radiographic success Randomized controlled trial, split mouth, blinded, valid with good efficacy; however, small sample size, & the follow up period was only 1 year Concluded that there was no statistically significant difference between the radiographic and clinical success of Ca(OH) 2 and MTA Recall examination at 3, 6, & 12 months Randomized Controlled Trial Table 1. Evidence based table for the randomized controlled trial comparing MTA and Ca(OH) 2

Author, Date, Location Population Intervention (number studied) Control (number studied) Outcome Critical Appraisal Comments Conclusion, Strength of Evidence and Classification Number of Sessions Sarris et al. 2006 Leeds Dental Institute, UK Domingeuz et al. 2005 University of Seville, Spain Finucane D & Kinirons MJ 1999 Northern Ireland, UK Walia et al. 2000 Chandigarh, India 17 non vital immature permanent incisors from 15 children (12 males, 3 females); mean age 11.7 years 26 non vital permanent incisors with open apices; 19 children (14 boys, 5 girls); age 6 9 years 44 non vital immature permanent incisors; age of children not mentioned 15 discoloured, non vital, permanent incisors with open apices; 12 children, age 7 16 years MTA N=17 Ca(OH) 2 N=26 Ca(OH) 2 N=44 Ca(OH) 2 N=15 None None None None Apical closure: Clinical Success=94.1%, Radiographic Success=76.5% Apical closure was obtained in 100% of cases Apical closure obtained in 100% of cases, 100% success within 1 year, with 80% requiring 1 or 2 dressings A pilot case study, no control groups, no blinding Case study, no control, no follow up after treatment, no blinding This is a case series; it had no control group, no follow up after treatment and no blinding Retrospective study, no control group, no blinding, no follow up after apical closure was obtained MTA has advantages over Ca(OH) 2, but cost and difficulty should be considered. Further studies required. Apexification with Ca(OH) 2 is effective in inducing apical closure Apexification is successful and is determined by rate of change of Ca(OH) 2 and the number of Ca(OH) 2 dressings placed Ca(OH)2 is successful treatment for apexification; factors are periapical infection, frequency of dressings and age 3 visits in total: 1 root canal, 2 MTA placement (only 1 for MTA itself), 3 obturation Mean 3.23 sessions Mean number of sessions is 1.9 and the average duration was 8 months Mean 1.8 sessions

Kinirons et al. 2001 UK 107 non vital immature permanent incisors; children Ca(OH) 2 N=107 None Apical closure obtained in 100% of cases; changing the Ca(OH) 2 more frequently increased rate of closure Retrospective study, not randomized, not blinded Strong evidence to show frequently changing the Ca(OH) 2 dressings the faster the formation of an apical barrier however it did not compare this to MTA nor was the study of preferred design ie not a RCT Pts were seen 6 weeks after initial placement and at 3 month intervals thereafter until barrier formation was detected Table 2. Summary of one sided reports on MTA or Ca(OH) 2