Mineral Trioxide Aggregate Apical Plugs in Teeth with Open Apical Foramina: A Retrospective Analysis of Treatment Outcome

Mineral Trioxide Aggregate Apical Plugs in Teeth with Open Apical Foramina: A Retrospective Analysis of Treatment Outcome

Clinical Research Mineral Trioxide Aggregate Apical Plugs in Teeth with Open Apical Foramina: A Retrospective Analysis of Treatment Outcome Johannes ...

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Clinical Research

Mineral Trioxide Aggregate Apical Plugs in Teeth with Open Apical Foramina: A Retrospective Analysis of Treatment Outcome Johannes Mente, DMD,* Nathalie Hage,* Thorsten Pfefferle, DMD,* Martin Jean Koch, MD, DMD, PhD,* Jens Dreyhaupt, DSc,† Hans Joerg Staehle, MD, DMD, PhD,* and Shimon Friedman, DMD ‡ Abstract Introduction: Teeth with open apical foramina present a challenge during root canal treatment, and little is known about the clinical outcome of treatment in such teeth. This retrospective study assessed healing of teeth with open apices managed by the placement of mineral trioxide aggregate apical plugs. Methods: Seventy-two patients with 78 teeth with apical resorption or excessive apical enlargement, treated between 2000 and 2006, were contacted for follow-up examination 12 to 68 months after treatment (median 30.9 months). Treatments were provided by supervised undergraduate students (27%), general dentists (32%), or dentists who had focused on endodontics (41%). The outcome based on clinical and radiographic criteria was assessed by calibrated examiners and dichotomized as ‘‘healed’’ or ‘‘disease.’’ Results: Of 56 teeth examined (72% recall), 84% were healed. Teeth without or with preoperative periapical radiolucency had a healed rate of 100% and 78%, respectively. None of the variables analyzed had a significant effect on the outcome. Conclusion: The results supported the management of open apical foramina with mineral trioxide aggregate apical plugs. (J Endod 2009;35:1354–1358)

Key Words Apexification, apical plug, healing, mineral trioxide aggregate, open apical foramina

From the *Department of Conservative Dentistry and the Institute of Medical Biometry and Informatics, Ruprecht-KarlsUniversity of Heidelberg, Germany; and ‡Discipline of Endodontics, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada. Address requests for reprints to Dr. Johannes Mente, University Clinic Heidelberg, Department of Conservative Dentistry Division of Endodontics, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. E-mail address: [email protected] 0099-2399/$0 - see front matter Copyright ª 2009 American Association of Endodontists. doi:10.1016/j.joen.2009.05.025 †

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onventional root canal filling techniques rely on the presence of a constriction at the apical level of the canal; therefore, the absence of the apical constriction because of incomplete root development, aggressive apical resorption, or iatrogenic enlargement presents a management challenge. Placement of the root filling in a canal with an open apical foramen carries the risk of root filling material extrusion (1), which may compromise the long-term outcome of treatment (2, 3). To avoid extrusion, compaction may be minimized, resulting in inadequate adaptation and seal (4, 5). Of the options currently available for the management of root canals with an open apex, the use of calcium hydroxide dressing to induce an apical hard tissue barrier (apexification) has gained the widest acceptance (5, 6). This procedure normally requires several visits to the dentist over a period of 5 to 20 months (5). During this period, the tooth is restored only temporarily, placing it at risk of coronal leakage and fracture (7). There is also the risk that the patient may fail to follow through with the required visits. In addition, the prolonged exposure to calcium hydroxide may adversely affect the mechanical properties of root dentin (8, 9), making it more susceptible to fracture (8–12). An alternative to apexification with calcium hydroxide is to seal the open apical foramen with a mineral trioxide aggregate (MTA) apical plug (13–16). This procedure can be completed in one (13) or two treatment sessions (14–16), making it possible to restore the tooth within a short timeframe while avoiding reliance on patient compliance and prolonged exposure of root dentin to calcium hydroxide. MTA-induced apexification may also result in a better consistency of the apical hard tissue barrier than is achieved with calcium hydroxide as suggested in an animal study (17). Clinical studies have reported that 77% to 85% of teeth with open apices healed completely 1 to 3 years after the placement of MTA apical plugs (13–16). The majority of the teeth included in these studies (13–16) were immature with incompletely developed roots, whereas a minority may have been teeth with open apical foramina resulting from apical resorption or overenlargement. The specific outcome in teeth with resorbed or mechanically enlarged apical foramina has not been reported. Therefore, the aim of this study was to assess healing in mature teeth with open apical foramina plugged with MTA.

Material and Methods The study protocol was approved by the Ethics Committee of the University of Heidelberg (Ref. 132/2006). Subjects for the study were identified from patients who received endodontic treatment at the Department of Conservative Dentistry at the University Hospital of Heidelberg from December 2000 to December 2006. The retrospective cohort was assembled to include teeth in which chronic apical periodontitis had led to radiographically evident apical resorption and teeth in which the apical constriction had been inadvertently enlarged as a result of overinstrumentation. In both groups of teeth, the diameter of the apical foramen was clinically confirmed to exceed that of a size 40 file. Subjects with compromised immune status who were pregnant at the time of follow-up, who declined to participate in the study, or who had incomplete pre- and intratreatment records were excluded. Subjects who met the inclusion criteria were contacted by letter and subsequently by telephone and invited for follow-up examinations. They were informed about the purpose

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Clinical Research and scope of the study and the nature of the examination. On the day of the examination, each subject was given a detailed explanatory information sheet and asked to sign a declaration of informed consent to participate in the study. Subjects were also invited to ask the examiner any questions concerning the study and the examination procedure.

Calibration Two investigators (NH and JT) were designated to perform the clinical follow-up examinations on all the subjects. Each investigator was calibrated by independently examining 21 patients during 1 day and by recording the following clinical parameters: response to cold and percussion, probing depth, attachment loss, furcation involvement, tooth mobility, and type and quality of coronal restoration. A tolerance range of 1 mm was defined for probing depth and attachment loss. The recorded data were analyzed for interexaminer reliability using absolute and relative frequencies of disagreement. One investigator (MK) was designated to perform all the radiographic interpretations. This examiner was calibrated by using the periapical index (PAI) calibration kit of 100 periapical radiographs (18). Intraexaminer reliability and interexaminer agreement with the calibration kit’s ‘‘gold standard’’ were assessed by using the Cohen kappa statistic. Endodontic Treatment Intervention Supervised undergraduate students (STs) treated 15 teeth (27%), general dentists (GDs) treated 18 teeth (32%), and dentists who had focused on endodontics for at least 3 years (ENs) treated 23 teeth (41%). Current endodontic treatment techniques were used. After rubber dam isolation and access cavity preparation, the canals were predominantly cleaned and shaped with nickel titanium hand K-type files (VDW, Munich, Germany) and intermittently irrigated with 3% sodium hypochlorite using a 27-G needle. In retreated teeth, additional irrigation was performed with 0.12% CHX solution (Glaxo Smith Kline GmbH, Bu¨hl, Germany). The dentists in the EN group also used nickel titanium rotary instruments (Flex Master, VDW, and GT-files; Dentsply-Maillefer, Ballaigues, Switzerland) in accordance with the manufacturer’s instructions. The working length was established with the aid of an apex locator (Raypex 4, VDW) and confirmed radiographically. Teeth were treated in two or more sessions; canals were medicated with calcium hydroxide (Hypocal SN; Merz Dental GmbH, Lu¨tjenburg, Germany) applied with a lentulo spiral (Dentsply-Maillefer), and the access was temporarily sealed with IRM (Dentsply, Konstanz, Germany). During the final treatment session, canals were finally flushed with 0.12% chlorhexidine (Glaxo Smith Kline GmbH) and dried with sterile paper points (VDW). When the apical foramen was confirmed to be open in excess of 0.4 mm, an MTA apical plug (Grey ProRoot MTA, Dentsply-Maillefer) was placed. Using an MTA delivery carrier (Dentsply-Maillefer), small portions of MTA were inserted and compacted apically with Machtou pluggers sizes 0, 1⁄2 , and 3⁄4 (Dentsply-Maillefer). All plugs were placed with the aid of a dental operating microscope (Zeiss, Oberkochen, Germany) and extended a minimum of 4 mm. The correct position and adequate extent of the MTA plug were confirmed radiographically. If the MTA plug was unsatisfactory (placed too short or showing voids), it was removed with a small ultrasonic tip (S 25; Satelec, Me´rignac Cedex, France) coupled with irrigation and replaced. In the ST group, one endodontically experienced instructor placed all the MTA apical plugs. The canal space coronal to the MTA apical plug was backfilled immediately after the placement of the plug. In 25 teeth (45%), it was filled with laterally condensed gutta-percha in conjunction with AH Plus sealer (Dentsply-Maillefer), in 23 teeth (41%) with injectable gutta-percha (Obtura II; Obtura Spartan, Fenton, MO) and AH Plus JOE — Volume 35, Number 10, October 2009

sealer, in five teeth (9%) with MTA, in two teeth (3.4%) with bonded composite resin (Tetric Ceram; Vivadent, Schaan, Lichtenstein), in one tooth (1.6%) with carrier-based gutta-percha (Thermafil, Dentsply-Maillefer) and AH Plus sealer. After completion of the root filling, the access cavities were sealed with composite resin (Herculite XRV; Kerr, West Collins, Orange, CA, or Tetric Ceram). Immediate posttreatment radiographs were taken using the parallel technique with an RWT film holder (KKD GmbH, Ellwangen, Germany) and 3  4 cm ISO classification E dental film (Kodak Ekta-Speed Plus; Carestream Health Inc, New York, NY).

Preoperative and Intraoperative Data Pre- and intraoperative information pertaining to clinical variables was gathered from the patients’ records and radiographs and entered into a specifically designed database. Preoperative data included sex, age, tooth location, number of roots, clinical signs and symptoms, response to cold test, tooth mobility, probing depths and attachment loss, furcation involvement, sinus tract, periapical radiolucency, signs of apical root resorption, and previous root filling. Intraoperative data included the Date of treatment completion, number of treatment sessions, cleaning and shaping technique, ISO size of apical enlargement, backfill technique, root-filling voids, complications, temporary seal, MTA extrusion, and treatment provider. Follow-up Examination The follow-up examinations were performed at different time intervals after treatment, ranging from 12 to 68 months, with a median follow-up period of 30.9 months. Recorded variables included the presence or absence of clinical signs and symptoms (sensitivity to percussion, sinus tract, pain, or discomfort), longitudinal root or tooth fracture, attachment loss, furcation involvement and loss of function, tooth mobility, and type and quality of the restoration and probing pocket depths. The coronal restoration was assessed clinically by visual inspection with mirror and explorer and radiographically by noting marginal gaps or decay. Periapical radiographs were exposed as described earlier. Signs of apical root resorption or extrusion of MTA were recorded, and the images were forwarded to the calibrated examiner for PAI-based interpretation. Outcome Assessment Radiographs were coded and stored and subsequently assessed by the designated examiner. Preoperative, posttreatment, and follow-up radiographs were examined independently in random sequence. They were evaluated in a darkened room by using an illuminated viewer box (Kentzler-Kaschner Dental GmbH, Ellwangen, Germany) with 2 magnification. Outcome was assessed on the basis of clinical and radiographic findings and was classified as ‘‘healed’’ when the PAI score was #2, and there were no signs of continuing root resorption, clinical symptoms, or loss of function. Outcome was classified as ‘‘disease’’ when one of the following was present: clinical signs and symptoms, longitudinal fracture, loss of function, PAI score $3, or continuing apical resorption. Multirooted teeth were assessed according to the highestscored root. Statistical Analysis Median, first and third quartile, minimum and maximum, and relative and absolute frequencies were calculated for descriptive analysis. Potential outcome predictors were fitted into generalized estimation equation (GEE) models, which allow an evaluation of dependent observations while accounting for the treatment of more than one tooth MTA Apical Plugs in Teeth with Open Apical Foramina

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Clinical Research TABLE 1. Outcome Distribution across Preoperative Variables Teeth Variable Age #45 y >45 y Sex Female Male Number of roots 1 $2 Tooth type Anterior Posterior Tooth location Maxilla Mandible Cause of wide foramen Apical resorption Excessive enlargement Signs and symptoms Absent Present Pulp status Responsive Nonresponsive Apical periodontitis Absent Present Type of treatment Initial treatment Retreatment

TABLE 2. Outcome Distribution across Intraoperative Variables

Healed

n

%

n

%

31 25

54 46

28 19

90 76

32 24

56 44

24 23

75 96

18 38

32 68

15 32

83 84

16 40

29 71

13 34

81 85

33 23

59 41

29 18

88 78

38 18

68 32

31 16

82 89

30 26

54 46

23 24

77 92

8 48

14 86

8 39

100 81

15 41

27 73

15 32

100 78

35 21

63 38

31 16

89 76

p value

Variable

0.14*

Root canal backfill technique Lateral compactionA Warm vertical compactionB Pure MTA fillingC OtherD Extruded MTA Absent Present Treatment providers Supervised undergraduate studentsE General dentistsF Dentists with practice limited to endodonticsG

0.06* 0.97* 0.74* 0.32* 0.50* 0.13* 0.58† 0.09† 0.22*

*Generalized estimation equations model. † Fisher exact test.

in individual subjects. For outcome predictors not possible to fit a GEE model (because of error in the estimation routine), a Fisher exact test was used instead. To ensure independent observations with this test, one tooth per subject was included; when a subject had two or more teeth treated, only one tooth was randomly chosen for the analysis. The data were processed with the SAS statistical package (Version 9.1; SAS Institute Inc, Cary, NC). Because of the exploratory nature of the study, no adjustment was made for multiple testing. Multivariate analysis, planned as a secondary step, was to be performed if one of the univariate analyses (GEE model or Fisher exact test) yielded significant differences. All tests were two-tailed and performed at a significance level of 0.05.

Results In the calibration process, there was no discrepancy in the results of the cold and percussion tests or in restoration quality recorded by both examiners for the 21 patients examined. A high level of consensus was also achieved with regard to probing depth (99.4%), attachment loss (99.5%), furcation involvement (99.0%), mobility (98.8%), and type of restoration (99.0%). For the PAI calibration results, the intraexaminer reliability was k = 0.77, indicating ‘‘substantial agreement’’ (19). The interexaminer agreement (examiner scores vs. the calibration kit ‘authorized scores’) was k = 0.82, indicating ‘‘almost perfect agreement’’ (19). Seventy-eight subjects (85 teeth) were initially identified for potential inclusion. With six subjects excluded because of incomplete pre- or intraoperative records, the study cohort included 72 subjects with 78 teeth who met the inclusion criteria. Of these, 50 subjects with 56 treated teeth (attending sample) were examined at follow-up (72% 1356

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Teeth

Healed

n

%

n

%

25 23

45 41

20 20

80 87

5 3

9 5

4 3

80 100

23 33

41 59

20 27

87 82

15

27

13

87

0.65* 1

18 23

32 41

13 21

72 91

0.11* 2

p value 0.69†

0.61*

*Generalized estimation equations model. † Fisher exact test. 1 E versus G. 2 F versus G.

recall). Of the subjects lost to follow-up, 10 did not respond to the recall, seven declined the recall, and five could not be contacted. Six subjects were included with two teeth each. Breakdown of the attending sample across the different variables examined is shown in Tables 1 through 3. In 38 teeth (68%), the root apex was lost because of external resorption, whereas in 18 teeth (32%) the apical foramen was excessively enlarged. Overall, 47 of the examined teeth (84%) were classified as healed (Fig. 1). Of the nine teeth (16%) classified as having disease, only three teeth presented with clinical symptoms at follow-up, suggesting that 53 teeth (95%) could be considered fully functional (20). In four teeth (7%), the periapical radiolucency was diminished in size but not completely resolved. The outcome is related to the recorded pre-, intra-, and postoperative variables in Tables 1 through 3. Minor differences in the healed rate were observed for several variables, whereas larger differences ($ 15%) were noted for four preoperative variables (sex, pulp status, apical periodontitis, and signs and symptoms), two intra-operative variables (experience of the treatment providers and root canal backfill technique), and one postoperative variable (type of restoration). Of specific interest was the finding that all 15 treated teeth without preoperative apical periodontitis healed compared with 32 of 41 (78%) teeth with apical periodontitis. Importantly, none of the differences observed was statistically significant.

Discussion This retrospective cohort study investigated the outcome of root canal treatment after apical MTA plugs were used to manage open apical foramina caused by root resorption because of inflammation/pathosis or excessive mechanical enlargement. The standardized study protocol was established in advance of the follow-up examinations, and it incorporated clinical and radiographic parameters derived from previous studies (2, 3, 20–22). Because of the explorative nature of the study, no sample size calculation was made and all eligible patients who had received endodontic treatment with MTA apical plugs in the defined study period were considered. The earliest subject entry time of December 2000 corresponded to the time at which MTA became

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Clinical Research TABLE 3. Outcome Distribution across Postoperative Variables Teeth Variable Quality of coronal restoration* Acceptable Unacceptable Unknown (tooth extracted) Type of restoration TemporaryA Amalgam fillingB Composite resin fillingC Crown and access sealed with composite resinD CrownE Lost restorationF Unknown (tooth extracted)G Post or screw after treatment Absent Present Unknown (tooth extracted)

n

%

Healed n

%

p value 0.72†

50 5 1

89 9 2

43 4 —

86 80 — 0.06†

0 0 28

0 0 50

— — 26

— — 93

10

18

7

70

17 0 1

30 0 2

14 — —

82 — —

0.10† 3

0.46† 4

0.98† 48 7 1

86 13 2

41 6 —

85 86 —

*Based on radiographic and clinical assessment. † Generalized estimation equations model. 3 C versus D 4 E versus D

available at the University Hospital of Heidelberg. The median follow-up interval of 30.9 months was sufficient to record a stable treatment outcome (21, 22). The recall rate of 72% was comparable to that in many endodontic follow-up studies (22), but it fell short of the 80% required for high level of evidence (22). The PAI index (18) was used to define the absence (PAI #2) or presence (PAI $3) of apical periodontitis, both before treatment and at follow-up. The PAI index had been validated as a reproducible, unbiased method for the interpretation of periapical radiographs (3, 18, 22). Independent, successfully calibrated examiners recorded the radiographic and clinical follow-up data. When taken together, the methodology parameters of this study were consistent with a level 2B evidence for assessment of prognosis (23). In total, 47 of the 56 examined teeth (84%) healed. As expected, the healed rate was higher for teeth without apical periodontitis (100%) than for those with apical periodontitis (78%), and it was within the reported range representing the current best evidence for the outcome of root canal treatment with conventional root filling (22). These results suggested that plugging open apical foramina with MTA yielded a predictable outcome at par with what can be expected in conventionally root-filled teeth with undisturbed apical constriction (2, 3, 20–22). Extrusion of the root filling in teeth with apical periodontitis may have an adverse effect on the outcome of treatment (2, 3, 24). In the present study, the healed rate was not affected by the extrusion of MTA beyond the root end (Fig. 1). Such extrusion is likely to occur in canals in which the apical foramen is wide open (1) and the material is not placed precisely. This finding corroborated a previous report on MTA apical plugs in dogs’ immature teeth in which extrusion did not affect the healing process (17). The lack of adverse effects from extrusion can be attributed to the good tissue compatibility of MTA, as has been suggested in several studies (25–29). MTA permits the growth

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Figure 1. (A) The midtreatment radiograph of mandibular first molar with apical periodontitis after insertion of apical MTA plugs. A small amount of extruded MTA is evident in the distal root. (B) A follow-up radiograph after 15 months. The outcome is classified as healed.

of cementum over its surface and reattachment of the periodontal ligament (17, 30, 31) so that the contact of extruded MTA with the periapical tissue is not an obstacle to healing. This is in contrast to most other root filling materials that, when extruded, elicit a host response aimed at removing the excess material (32, 33). Preoperative apical periodontitis has an adverse effect on treatment outcome, with a reported difference in healed rates of 10% to 15% between teeth with or without apical periodontitis (22). In the present study, the observed difference of 22% was not statistically significant. The lack of significance suggested an underpowered analysis because of the small and unequally distributed sample. A post hoc power analysis using the confidence limits of the exact binomial distribution suggested that at least 373 teeth would be required (261 teeth with and 112 teeth without apical periodontitis) to achieve 80% power and 5% level of significance for a two-tailed test. Because the present study project will continue to include new patients prospectively, this prognostic factor will be re-evaluated in the future with a larger sample size. Considering the low power of analysis, which did not support the significance of the strongest outcome predictor (apical periodontitis), no other variables could be expected to turn out to be significant. This was also true of the treatment providers’ level of experience. The study results suggested that the management of MTA apical plugs yielded a favorable outcome even when performed by less experienced clinicians. Furthermore, the favorable results achieved by the supervised students with the help of an experienced instructor suggested that

MTA Apical Plugs in Teeth with Open Apical Foramina

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Clinical Research when the apical foramen is inadvertently enlarged by the student treating the tooth or it is found open because of resorption, treatment of the tooth can be completed within the undergraduate clinic without necessitating referral to a specialist. Where curriculum and time permit, students may even be taught and allowed to practice how to place MTA apical plugs, which could benefit them in the future. Recently, the suggestion was made to add an accelerator (CaCl2) to MTA in order to minimize the pore diameter of MTA apical plugs and thus the risk if apical leakage (34). Adding the accelerator considerably reduces the setting time (35). An accelerated set may be an advantage when MTA is used for perforation repair or root-end filling; however, it may be a disadvantage during placement of MTA apical plugs. If the radiographic check suggests that the plug location or density is not satisfactory, it can be removed and replaced as long as it is not set. The MTA apical plugs in this study were at least 4-mm deep, whereas the rest of the canal space was filled with gutta-percha and sealer, composite resin, or MTA. In vitro studies have suggested that a 4-mm depth of the MTA plugs is sufficient to provide an adequate seal (36, 37) and that complete filling of the root canal with MTA may not provide a better seal than a 4-mm MTA plug combined with a gutta-percha and sealer backfill (38). In conclusion, the results of this explorative study suggested that MTA was suitable for the management of teeth with open apical foramina as a result of apical resorption or excessive mechanical enlargement. The placement of MTA apical plugs in such teeth resulted in healing outcomes (84% healed) at par with those reported for conventionally managed teeth (22) and for immature teeth with incomplete root development (14, 15). The outcome of the apical plug procedure was favorable even when performed by students supervised by an experienced instructor, and it was unaffected by extrusion of MTA outside the root end. Future prospective studies with larger samples are required to investigate potential outcome predictors for this valuable clinical procedure.

Acknowledgment The authors wish to thank Mr. Jens Trautmann for his valuable help with this study, and Mrs. Joanna Voerste and Mr. Philip Benjamin for their assistance in the preparation of this manuscript.

References 1. Ritchie GM, Anderson DM, Sakumura JS. Apical extrusion of thermoplasticized Gutta-percha used as a root canal filling. J Endod 1988;14:128–32. 2. Sjo¨gren U, Hagglund B, Sundqvist G, et al. Factors affecting the long-term results of endodontic treatment. J Endod 1990;16:498–504. 3. Ørstavik D, Qvist V, Stoltze K. A multivariate analysis of the outcome of endodontic treatment. Eur J Oral Sci 2004;112:224–30. 4. Kerezoudis NP, Valavanis D, Prountzos F. A method of adapting gutta-percha master cones for obturation of open apex cases using heat. Int Endod J 1999;32:53–60. 5. Rafter M. Apexification: a review. Dent Traumatol 2005;21:1–8. 6. Dominguez Reyes A, Munoz Munoz L, Aznar Martin T. Study of calcium hydroxide apexification in 26 young permanent incisors. Dent Traumatol 2005;21:141–5. 7. Heling I, Gorfil C, Slutzky H, et al. Endodontic failure caused by inadequate restorative procedures: review and treatment recommendations. J Prosthet Dent 2002;87:674–8. 8. Andreasen JO, Farik B, Munksgaard EC. Long-term calcium hydroxide as a root canal dressing may increase risk of root fracture. Dent Traumatol 2002;18:134–7. 9. Rosenberg B, Murray PE, Namerow K. The effect of calcium hydroxide root filling on dentin fracture strength. Dent Traumatol 2007;23:26–9. 10. Cvek M. Prognosis of luxated non-vital maxillary incisors treated with calcium hydroxide and filled with gutta-percha. A retrospective clinical study. Endod Dent Traumatol 1992;8:45–55.

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Mente et al.

11. Andreasen JO, Munksgaard EC, Bakland LK. Comparison of fracture resistance in root canals of immature sheep teeth after filling with calcium hydroxide or MTA. Dent Traumatol 2006;22:154–6. 12. Hatibovic´-Kofman S, Raimundo L, Zheng L, et al. Fracture resistance and histological findings of immature teeth treated with mineral trioxide aggregate. Dent Traumatol 2008;24:272–6. 13. Simon S, Rilliard F, Berdal A, et al. The use of mineral trioxide aggregate in one-visit apexification treatment: a prospective study. Int Endod J 2007;40:186–97. 14. Holden DT, Schwartz SA, Kirkpatrick TC, et al. Clinical outcomes of artificial rootend barriers with mineral trioxide aggregate in teeth with immature apices. J Endod 2008;34:812–7. 15. Sarris S, Tahmassebi JF, Duggal MS, et al. 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;24:79–85. 16. Witherspoon DE, Small JC, Regan JD, et al. Retrospective analysis of open apex teeth obturated with mineral trioxide aggregate. J Endod 2008;34:1171–6. 17. Shabahang S, Torabinejad M, Boyne PP, et al. A comparative study of root-end induction using osteogenic protein-1, calcium hydroxide, and mineral trioxide aggregate in dogs. J Endod 1999;25:1–5. 18. Ørstavik D, Kerekes K, Eriksen HM. The periapical index: a scoring system for radiographic assessment of apical periodontitis. Endod Dent Traumatol 1986;2:20–34. 19. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977;33:159–74. 20. de Chevigny C, Dao TT, Basrani BR, et al. Treatment outcome in endodontics: the Toronto study–phase 4: initial treatment. J Endod 2008;34:258–63. 21. Ørstavik D. Time-course and risk analyses of the development and healing of chronic apical periodontitis in man. Int Endod J 1996;29:150–5. 22. Friedman S. Expected outcomes in the prevention and treatment of apical periodontitis. In: Orstavik D, Pitt Ford T, eds. Essential Endodontology: Prevention and Treatment of Apical Periodontitis. 2nd ed. Blackwell Munksgaard Ltd; 2008: 408–69. 23. Phillips B, Ball C, Sackett D, Badenoch D, et al. Centre for Evidence-Based Medicine at Oxford. Accessed 2001. Available at: http://www.cebm.net/index.aspx?o = 1025. 24. Kojima K, Inamoto K, Nagamatsu K, et al. Success rate of endodontic treatment of teeth with vital and nonvital pulps. A meta-analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:95–9. 25. Koh ET, McDonald F, Pitt Ford TR, et al. Cellular response to mineral trioxide aggregate. J Endod 1998;24:543–7. 26. Zhu Q, Haglund R, Safavi KE, et al. Adhesion of human osteoblasts on root-end filling materials. J Endod 2000;26:404–6. 27. Pistorius A, Willershausen B, Briseno Marroquin B. Effect of apical root-end filling materials on gingival fibroblasts. Int Endod J 2003;36:610–5. 28. Ribeiro DA, Duarte MA, Matsumoto MA, et al. Biocompatibility in vitro tests of mineral trioxide aggregate and regular and white Portland cements. J Endod 2005;31:605–7. 29. Yoshimine Y, Ono M, Akamine A. In vitro comparison of the biocompatibility of mineral trioxide aggregate, 4META/MMA-TBB resin, and intermediate restorative material as root-end-filling materials. J Endod 2007;33:1066–9. 30. Al-Daafas A, Al-Nazhan S. Histological evaluation of contaminated furcal perforation in dogs’ teeth repaired by MTA with or without internal matrix. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2007;103:e92–9. 31. Holland R, Bisco Ferreira L, de Souza V, et al. Reaction of the lateral periodontium of dogs’ teeth to contaminated and noncontaminated perforations filled with mineral trioxide aggregate. J Endod 2007;33:1192–7. 32. Bernath M, Szabo J. Tissue reaction initiated by different sealers. Int Endod J 2003; 36:256–61. 33. Friend LA, Browne RM. Tissue reactions to some root filling materials. Br Dent J 1968;125:291–8. 34. Hong ST, Bae KS, Baek SH, et al. Microleakage of accelerated mineral trioxide aggregate and Portland cement in an in vitro apexification model. J Endod 2008;34:56–8. 35. Kogan P, He J, Glickman GN, et al. The effects of various additives on setting properties of MTA. J Endod 2006;32:569–72. 36. Valois CR, Costa ED Jr. Influence of the thickness of mineral trioxide aggregate on sealing ability of root-end fillings in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2004;97:108–11. 37. Lawley GR, Schindler WG, Walker WA 3rd, et al. Evaluation of ultrasonically placed MTA and fracture resistance with intracanal composite resin in a model of apexification. J Endod 2004;30:167–72. 38. Martin RL, Monticelli F, Brackett WW, et al. Sealing properties of mineral trioxide aggregate orthograde apical plugs and root fillings in an in vitro apexification model. J Endod 2007;33:272–5.

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