Intentional foraminal enlargement: a critical review. Paper published in the journal Endodontic Practice (UK), in partnership with Profs. Dr. Ricardo Machado (SC) and Frederico Martinho (Univ. Maryland USA).
Work translated:
SUMMARY
The endodontic literature has frequently demonstrated the difficulties in obtaining an adequate cleaning and sanitation process, especially in the final millimeters of root canals. Moreover, in some cases, the endodontic infection is found beyond the limits of the apical constriction, i.e., in the apical foramen or beyond (extraradicular biofilm). The intentional enlargement of the apical foramen aims to reduce the microbial contingent in these areas to levels favorable to repair. Therefore, the aim of this article was to perform a critical analysis based on the literature, evaluating the advantages, disadvantages and local and systemic risks of this procedure. After the literature review, it was possible to conclude that there is no scientific evidence supporting the performance of foraminal widening in human beings. Moreover, the methodological design of future studies where this procedure will be performed should be even more careful because the literature consulted in this article reiterates that this procedure offers both local and systemic risks.
Keywords: apical foramen; foraminal enlargement; endodontic treatment.
INTRODUCTION
Endodontics is one of the dental specialties that has undergone the most changes in its paradigms due to technical and scientific developments. However, the binomial "cleaning and shaping"(1), continues to be one of the pillars of the specialty, especially in cases where there is contamination of the root canal system.
Due to the anatomical complexity, the literature has demonstrated, throughout history, the difficulties in obtaining an adequate cleaning and sanitation process, especially in the apical thirds(2). In addition, in some cases, the endodontic infection is found beyond the limits of apical constriction, i.e., in the apical foramen or beyond (extraradicular biofilm)(3-5). In these situations, the intentional instrumentation of the apical foramen aims to reduce the microbial contingent in these areas to levels favorable to the repair(6, 7). Previous studies have shown encouraging results when intentional foraminal enlargement is performed due to the mechanical action of the instruments and the chemical action of irrigating solutions(8-12).
Therefore, the aim of this article is to perform a literature review critically analyzing the probable benefits and risks of intentional foraminal enlargement considering possible local and systemic repercussions.
LOCAL IMPACT
Anatomical considerations
Undeniably, in teeth where there is pulp necrosis and periradicular lesions, the whole path of the root canal is contaminated(5, 13-16). For this reason, there is a common sense in the literature that foraminal patency is able to clear the apical foramen and promote a microbiological disorganization in this region by the use of a thin caliber instrument lightly touching its walls(17, 18).
The foraminal enlargement, in turn, is performed by means of different techniques and instruments. It consists in the mechanical enlargement of the apical foramen aiming at its decontamination through the excision of contaminated dentin and cementum(6, 19). In teeth with pulp vitality, previous studies have demonstrated the favoring of tissue repair due to a closer contact of calcium hydroxide with periradicular tissues(20) and the stimulation of defense cells after foraminal enlargement(7).
However, to perform a safe foraminal enlargement, it would be necessary to determine the shape and diameter of the apical foramen, which is clinically impossible(21, 22)). In most dental groups, because the apical foramen has an oval shape, conventional endodontic instruments are not able to fulfill this purpose(23-26). Consequently, adequate cleaning cannot be achieved(21, 26, 27).
Moreover, a number of clinical studies have shown a high frequency of instrument fractures in the apical third due to its irregular anatomy and the degree of constriction of this region(28, 29). In addition, considering that, especially in posterior teeth, the apical foramen is located laterally to the root apex(30), foraminal enlargement may predispose to an even higher incidence of fractures.
Another limiting factor for foraminal enlargement is the impossibility of foraminal patency. This occurs due to the presence of abrupt curvatures, two or more main apical foramen, apical deltas or complete or incomplete isthmus(31)
Taking the above into consideration, foraminal enlargement, although a microbiologically plausible idea, cannot always be performed. Moreover, in controlled clinical studies with robust samples and adequate inclusion and exclusion criteria(32-35) there are no reports of intentional foraminal enlargement in the clinical protocols adopted. Yet success rates exceed 85% even in cases of radiographically visible necrosis and/or periradicular lesions(32-34)).
Extravasation of sodium hypochlorite, calcium hydroxide and obturating materials
Sodium hypochlorite is the most widely accepted and used irrigating substance worldwide(36-39). However, it has a highly harmful effect when extravasated into the periradicular tissues, maxillary sinus or when injected into the gingival mucosa(40-43). The most common consequences of this accident are severe pain, immediate inflammation of the affected area, extension of the edema to the face, lips and infraorbital region, hemorrhage from the root canal, interstitial hemorrhage with ecchymosis of the skin and mucosa, secondary infection and paresthesia(44).
Another drug used in endodontics that has reports of extravasation with negative consequences is calcium hydroxide. Fava in 1993 and Marais & Van der Vyver in 1996 reported cases of extravasation of calcium hydroxide into the maxillary sinus causing acute pain and foreign body reaction(45, 46). Johannessen et al. in 2003 reported a case of calcium hydroxide extravasation into the mandibular canal with acute pain and paresthesia(47). Neural lesions(48), severe periradicular inflammation and the need for extraction of the tooth involved(49) and the persistence of periradicular lesions have also been associated with calcium hydroxide extrusion(50).
The obturating materials (mainly the solid ones) are also responsible for a series of complications after their extravasation(51-55) such as; the incidence of periradicular compromises of the foreign body type, flare-ups and postoperative pain by activation of exacerbated inflammatory responses(51-62). All material extruded beyond the apical foramen is irritating to the peri-radicular tissues to a greater or lesser extent. There is no scientific evidence proving any benefit that justifies the intentional extravasation of irrigants, pastes and cements(63-67)
It is licit to consider the hypothesis that the greater the enlargement of the apical foramen, the greater the chances of extravasation of any substance used in the root canal(44). However, more research is needed to prove this hypothesis.
SYSTEMIC REPERCUSSIONS
Patients who are taking or have recently taken bisphosphonates
Bisphosphonates are drugs used for the treatment of bone diseases and in the prevention of tumor metastasis(68). Their chronic use is directly related to osteonecrosis of the jaws after the performance of dental procedures(68-71) As they are drugs widely used nowadays, the dental surgeon must be aware of some probable effects capable of influencing the prognosis of the treatment.
Specifically related to Endodontics, some important care must be considered such as:
- The use of antiseptic substances such as chlorhexidine should be performed in order to reduce the bacterial load of the oral cavity(72) and the risk of bacteremia due to possible trauma to the soft tissues during treatment(68).
- Because vascularization is compromised, constituting a greater risk of osteonecrosis, and considering that bisphosphonates exert an antiangiogenic action, the use of anesthetics with vasoconstrictors should be avoided(68, 73, 74).
- Special care should be taken in order to reduce the data to the gingival tissue as much as possible(68, 75).
- Obturation techniques that offer lower risks of overburation and overextension should be prioritized(34, 68, 76).
According to Katz in 2005 and Edwards et al. in 2008(70, 71), in patients who are using or have recently used these drugs, one of the main precautions is to establish a working length close to the apical constriction in order to reduce debris extrusion and exacerbated inflammatory reactions during and after treatment. In addition, foraminal patency itself should be avoided(68). This can considerably increase the chances of bacteremia(68, 77). Such statements are based on the fact that bisphosphonates directly interfere with the bone remodeling process and the inhibition of chemical mediators of the inflammatory process(70, 71).
Considering the above, in view of the need for endodontic interventions in patients who are or have recently been taking bisphosphonates, it seems obvious that the intentional enlargement of the apical foramen is a completely contraindicated procedure.
Patients with coagulation disorders or taking anticoagulants
In healthy patients hemostasis is associated with 4 main factors: blood vessel walls, blood platelets, the coagulation system, and the fibrinolytic system. The constriction of blood vessels constitutes the first step, followed by platelet adhesion and aggregation, and fibrin deposition. Then the coagulation process is guided by physiological anticoagulants. Activation of fibrinolysis is triggered by the presence of fibrin and tissue-type plasminogen activators at the site of fibrin formation, a process regulated by physiologic inhibitors such as 2-antiplasmin, histidine-rich glycoprotein, and plasminogen activator inhibitor(78, 79).
In patients with coagulopathies or on anticoagulants, this process is completely altered, resulting in excessive bleeding even from small stimuli. Therefore, these patients may neglect their oral health because of bleeding gums during hygiene and, consequently, greater risks of periodontal disease and caries can be observed. Therefore, the dental surgeon should be aware of the impact of blood disorders or the use of anticoagulants on the treatment of his patients(80-82)
Specifically related to Endodontics, in patients with coagulation disorders or under use of anticoagulants, this should be, whenever possible, the first choice over the extraction of the dental element. However, the process of cleaning and sanitation must be confined to the limits of the root canal(83). Therefore, foraminal instrumentation seems to be completely contraindicated.
Patients at high risk of bacteremia
Several systemic complications have been reported as a consequence of dental infections. Among the most frequent are bacterial endocarditis, myocardial infarction, brain abscess, and bone, antral, and blood infections(84-90)).
During the performance of endodontic treatment, the cleaning and shaping process has the potential to insert bacteria into the bloodstream and lymphatic system(89, 91-93). Blood samples collected during and after endodontic treatment of teeth with pulp necrosis revealed the presence of the same bacteria both in the root canal system and in the bloodstream of the patients evaluated(77, 94-96)Therefore, microorganisms present in the root canal can reach and settle in places far from their place of origin(93).
Extrusion of debris during the cleaning and disinfection process of the root canal system has been frequently demonstrated, regardless of the systems and techniques used(97-100).
Specifically correlating debris extrusion and the apical limit of instrumentation, Tinaz et al. in 2005 conducted a study in order to compare debris extrusion during manual and rotary instrumentation on teeth that had the constriction and apical foramen intentionally dilated(101). Fifty-two teeth were divided into two groups with 26 specimens each according to the instrumentation technique (manual with K-type instruments and rotary using the Profile .04 Taper Series 29 system). These were further divided into two subgroups where the apical foramen was intentionally widened by the action of instruments n. 15 and n. 30, two millimeters beyond the apical foramen. Sodium hypochlorite 2.6% was the irrigating solution used. No statistically significant differences were found regarding debris extrusion comparing manual and rotary instrumentation. However, in both techniques there was a tendency to greater extrusion of debris when the constriction and apical foramen had been intentionally more dilated.
Therefore, an instrumentation limit beyond the apical foramen should be avoided in patients with a high risk of bacteremia considering the higher risk of systemic spread of microorganisms(15, 77, 85, 91, 102).
CONCLUDING REMARKS
The difficulties to obtain an adequate cleaning and sanitation process, especially in the final millimeters of the root canals, have been constantly demonstrated(2, 85, 103-105). Consequently, a wider range of instrumentation has been advocated for a more effective action of both endodontic instruments(106, 107) and irrigating solutions(108-110) and intracanal medications(12).
Moreover, in some cases, the endodontic infection is found beyond the limits of the apical constriction, that is, in the apical foramen or beyond (extraradicular biofilm)(3-5). In these situations, the intentional instrumentation of the apical foramen aims to reduce the microbial contingent in these areas to levels favorable to the repair(6, 7).
However, the great truth is that, so far, there are only animal studies comparing success rates between intentional instrumentation of the apical foramen and conventional instrumentation limits (near the apical constriction)(6, 20). Even considering the positive results found in these researches, there is no way to infer that this procedure will have the same positive biological responses in human beings. According to the precepts of Evidence-Based Dentistry, some criteria need to be respected and followed before performing any intervention in humans. First, laboratory studies must be performed to build a plausible hypothesis to be tested in vivo. Next, in vivo studies in animals should be performed to observe possible toxic or harmful potentials of substances, drugs, or surgical interventions. Finally, controlled longitudinal clinical studies are needed to observe the results obtained proving or not the advantages or disadvantages of the hypothesis previously considered(111-114).
Specifically speaking about intentional foraminal widening, there is no scientific evidence to support its realization. To date, there is not one randomized clinical study with longitudinal follow-ups evaluating the success rates of endodontic treatments or retreatments where the apical limits of instrumentation were established at or beyond the apical foramen. On the other hand, considerable success rates have been found in controlled clinical studies with robust sample sizes and adequate inclusion and exclusion criteria where apical limits of instrumentation were determined close to the apical constriction(5, 33, 34).
Obviously, considering the scientific dynamics, the impacts of intentional enlargement of the apical foramen in relation to the success of endodontic therapy should be evaluated. However, the methodological designs of these studies should be even more careful, because the literature consulted in this article reiterates that this procedure offers both local and systemic risks to the patient.
1. Schilder H. Cleaning and shaping the root canal. Dent Clin North Am 1974;18:269-296.
2. Paqué F, Ganahl D, Peters OA. Effects of root canal preparation on apical geometry assessed by micro-computed tomography. J Endod 2009;35(7):1056-1059.
7. Parris J, Wilcox L, Walton R. Effectiveness of apical clearing: histological and radiographical evaluation. Journal of Endodontics 1994;20(5):219-224.
10. Fornari V, Silva-Sousa Y, Vanni J, Pécora J, Versiani M, Sousa-Neto M. Histological evaluation of the effectiveness of increased apical enlargement for cleaning the apical third of curved canals. International Endodontic Journal 2010;43(11):988-994.
11. Albrecht LJ, Baumgartner JC, Marshall JG. Evaluation of apical debris removal using various sizes and tapers of ProFile GT files. Journal of Endodontics 2004;30(6):425-428.
12. Card SJ, Sigurdsson A, Ørstavik D, Trope M. The effectiveness of increased apical enlargement in reducing intracanal bacteria. Journal of Endodontics 2002;28(11):779-783.
13. Tronstad L, Barnett F, Cervone F. Periapical bacterial plaque in teeth refractory to endodontic treatment. Dental Traumatology 1990;6(2):73-77.
14. Nair P, Henry S, Cano V, Vera J. Microbial status of apical root canal system of human mandibular first molars with primary apical periodontitis after "one-visit" endodontic treatment. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2005;99(2):231-252.
15. Siqueira Jr JF, Rôças IN. Clinical implications and microbiology of bacterial persistence after treatment procedures. Journal of Endodontics 2008;34(11):1291-1301. e1293.
16. Craig Baumgartner J, Falkler WA. Bacteria in the apical 5 mm of infected root canals. Journal of endodontics 1991;17(8):380-383.
17. Buchanan L. Management of the curved root canal. Journal of the California Dental Association 1989;17(4):18.
18. Souza RA. The importance of apical patency and cleaning of the apical foramen on root canal preparation. Brazilian dental journal 2006;17(1):6-9.
19. Silva EJNL, Menaged K, Ajuz N, Monteiro MRFP, de Souza Coutinho-Filho T. Postoperative pain after foraminal enlargement in anterior teeth with necrosis and apical periodontitis: a prospective and randomized clinical trial. Journal of endodontics 2013;39(2):173-176.
20. Holland R, Nery M, De Mello W, De Souza V, Bernabé P. Root canal treatment with calcium hydroxide: II. Effect of instrumentation beyond the apices. Oral Surgery, Oral Medicine, Oral Pathology 1979;47(1):93-96.
21. Abarca J, Zaror C, Monardes H, Hermosilla V, Muñoz C, Cantin M, et al. Morphology of the Physiological Apical Foramen in Maxillary and Mandibular First Molars. INTERNATIONAL JOURNAL OF MORPHOLOGY 2014;32(2):671-677.
22. Dummer PM, McGinn J, Rees DG. The position and topography of the apical canal constriction and apical foramen. International Endodontic Journal 1984;17(4):192-198.
23. Akisue E, Gratieri SD, Barletta FB, Caldeira CL, Grazziotin-Soares R, Gavini G. Not all electronic foramen locators are accurate in teeth with enlarged apical foramina: an in vitro comparison of 5 brands. Journal of endodontics 2014;40(1):109-112.
24. Goldberg F, Massone EJ. Patency file and apical transportation: an in vitro study. Journal of endodontics 2002;28(7):510-511.
25. Herrera M, Ábalos C, Lucena C, Jiménez-Planas A, Llamas R. Critical diameter of apical foramen and of file size using the Root ZX apex locator: an in vitro study. Journal of endodontics 2011;37(9):1306-1309.
26. Marroquín BB, El-Sayed MA, Willershausen-Zönnchen B. Morphology of the physiological foramen: I. Maxillary and mandibular molars. Journal of Endodontics 2004;30(5):321-328.
27. Wu M-K, R'oris A, Barkis D, Wesselink PR. Prevalence and extent of long oval canals in the apical third. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2000;89(6):739-743.
28. Ehrhardt IC, Zuolo ML, Cunha RS, De Martin AS, Kherlakian D, de Carvalho MCC, et al. Assessment of the separation incidence of Mtwo files used with preflaring: prospective clinical study. Journal of endodontics 2012;38(8):1078-1081.
29. Madarati AA, Hunter MJ, Dummer PM. Management of intracanal separated instruments. Journal of endodontics 2013;39(5):569-581.
30. Pineda F, Kuttler Y. Mesiodistal and buccolingual roentgenographic investigation of 7,275 root canals. Oral Surgery, Oral Medicine, Oral Pathology 1972;33(1):101-110.
31. Villas-Bôas MH, Bernardineli N, Cavenago BC, Marciano M, del Carpio-Perochena A, de Moraes IG, et al. Micro-Computed Tomography Study of the Internal Anatomy of Mesial Root Canals of Mandibular Molars. Journal of endodontics 2011;37(12):1682-1686.
32. Coldero L, McHugh S, MacKenzie D, Saunders W. Reduction in intracanal bacteria during root canal preparation with and without apical enlargement. International Endodontic Journal 2002;35(5):437-446.
33. Imura N, Pinheiro ET, Gomes BP, Zaia AA, Ferraz CC, Souza-Filho FJ. The outcome of endodontic treatment: a retrospective study of 2000 cases performed by a specialist. Journal of Endodontics 2007;33(11):1278-1282.
34. Liang Y-H, Jiang L-M, Jiang L, Chen X-B, Liu Y-Y, Tian F-C, et al. Radiographic healing after a root canal treatment performed in single-rooted teeth with and without ultrasonic activation of the irrigant: a randomized controlled trial. Journal of endodontics 2013;39(10):1218-1225.
35. Ricucci D, Russo J, Rutberg M, Burleson JA, Spångberg LS. A prospective cohort study of endodontic treatments of 1,369 root canals: results after 5 years. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2011;112(6):825-842.
36. Guneser MB, Arslan D, Usumez A. Tissue Dissolution Ability of Sodium Hypochlorite Activated by Photon-initiated Photoacoustic Streaming Technique. Journal of endodontics 2015;41(5):729-732.
37. Wong DT, Cheung GS. Extension of bactericidal effect of sodium hypochlorite into dentinal tubules. Journal of endodontics 2014;40(6):825-829.
38. Zou L, Shen Y, Li W, Haapasalo M. Penetration of sodium hypochlorite into dentin. Journal of endodontics 2010;36(5):793-796.
39. Stojicic S, Zivkovic S, Qian W, Zhang H, Haapasalo M. Tissue dissolution by sodium hypochlorite: effect of concentration, temperature, agitation, and surfactant. Journal of endodontics 2010;36(9):1558-1562.
40. Kerbl FM, DeVilliers P, Litaker M, Eleazer PD. Physical Effects of Sodium Hypochlorite on Bone: An< i> Ex Vivo</i> Study. Journal of endodontics 2012;38(3):357-359.
41. Pashley E, Birdsong N, Bowman K, Pashley D. Cytotoxic effects of NaOCl on vital tissue. Journal of endodontics 1985;11(12):525-528.
42. Ehrich DG, Brian Jr JD, Walker WA. Sodium hypochlorite accident: inadvertent injection into the maxillary sinus. Journal of endodontics 1993;19(4):180-182.
43. Kavanagh C, Taylor J. Inadvertent injection of sodium hypochlorite into the maxillary sinus. British dental journal 1998;185(7):336-337.
44. Hülsmann M, Hahn W. Complications during root canal irrigation-literature review and case reports. International Endodontic Journal 2000;33(3):186-193.
45. Fava L. Calcium hydroxide paste in the maxillary sinus: a case report. International endodontic journal 1993;26(5):306-310.
46. Marais J, Van Der Vyver P. Invasion of the maxillary sinus with calcium hydroxide. The Journal of the Dental Association of South Africa= Die Tydskrif van die Tandheelkundige Vereniging van Suid-Afrika 1996;51(5):279.
47. Ahlgren FK, Johannessen AC, Hellem S. Displaced calcium hydroxide paste causing inferior alveolar nerve paraesthesia: report of a case. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2003;96(6):734-737.
48. Olsen JJ, Thorn J, Korsgaard N, Pinholt EM. Nerve lesions following apical extrusion of non-setting calcium hydroxide: A systematic case review and report of two cases. Journal of Cranio-Maxillofacial Surgery 2014;42(6):757-762.
49. Hanson C, Macluskey M. Irreversible local sequelae of inadvertent extrusion of calcium hydroxide intra-canal medication: a case report. Oral Surgery 2013;6(3):161-164.
50. Ioannidis K, Thomaidis V, Fiska A, Lambrianidis T. Lack of periradicular healing and gradually increasing swelling two years after intentional extrusion of calcium hydroxide into periapical lesion: report of a case. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2010;109(6):e86-e91.
51. Alves FR, Coutinho MS, Gonçalves LS. Endodontic-related facial paresthesia: systematic review. Journal (Canadian Dental Association) 2014;80:e13-e13.
52. Gluskin A. Mishaps and serious complications in endodontic obturation. Endodontic Topics 2005;12(1):52-70.
53. González-Martín M, Torres-Lagares D, Gutiérrez-Pérez JL, Segura-Egea JJ. Inferior alveolar nerve paresthesia after overfilling of endodontic sealer into the mandibular canal. Journal of endodontics 2010;36(8):1419-1421.
54. Köseogˇlu BG, Tanrıkulu Ş, Sübay RK, Sencer S. Anesthesia following overfilling of a root canal sealer into the mandibular canal: a case report. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2006;101(6):803-806.
55. Rowe A. Damage to the inferior dental nerve during or following endodontic treatment. British dental journal 1983;155(9):306-307.
56. Georgopoulou M, Sikaras S, Anastasiadis P. [Pain after obturation of the root canals]. Hellenika stomatologika chronika. Hellenic stomatological annals 1987;32(4):249-254.
57. Nair P. Pathogenesis of apical periodontitis and the causes of endodontic failures. Critical Reviews in Oral Biology & Medicine 2004;15(6):348-381.
58. Oliet S. Single-visit endodontics: a clinical study. Journal of Endodontics 1983;9(4):147-152.
59. Faria-Júnior N, Tanomaru-Filho M, Berbert F, Guerreiro-Tanomaru J. Antibiofilm activity, pH and solubility of endodontic sealers. International endodontic journal 2013;46(8):755-762.
60. Saleh I, Ruyter I, Haapasalo M, Ørstavik D. Survival of Enterococcus faecalis in infected dentinal tubules after root canal filling with different root canal sealers in vitro. International Endodontic Journal 2004;37(3):193-198.
61. Seltzer S, Naidorf IJ. Flare-ups in endodontics: I. Etiological factors. Journal of Endodontics 1985;11(11):472-478.
62. Siqueira J. Microbial causes of endodontic flare-ups. International Endodontic Journal 2003;36(7):453-463.
63. Nair PR, Sjögren U, Krey G, Sundqvist G. Therapy-resistant foreign body giant cell granuloma at the periapex of a root-filled human tooth. Journal of Endodontics 1990;16(12):589-595.
64. Strindberg LZ. The dependence of the results of pulp therapy on certain factors: an analytic study based on radiographic and clinical follow-up examinations. Mauritzon; 1956.
65. Yusuf H. The significance of the presence of foreign material periapically as a cause of failure of root treatment. Oral Surgery, Oral Medicine, Oral Pathology 1982;54(5):566-574.
66. Sjögren U, Hägglund B, Sundqvist G, Wing K. Factors affecting the long-term results of endodontic treatment. Journal of Endodontics 1990;16(10):498-504.
67. Engstrom B. Correlation of positive culture with the prognosis for root canal treatment. Odontol. Revy 1964;15:257-270.
68. Moinzadeh AT, Shemesh H, Neirynck N, Aubert C, Wesselink P. Bisphosphonates and their clinical implications in endodontic therapy. International endodontic journal 2013;46(5):391-398.
69. Sarathy AP, Bourgeois Jr SL, Goodell GG. Bisphosphonate-associated osteonecrosis of the jaws and endodontic treatment: two case reports. Journal of endodontics 2005;31(10):759-763.
70. Katz H. Endodontic implications of bisphosphonate-associated osteonecrosis of the jaws: a report of three cases. Journal of endodontics 2005;31(11):831-834.
71. Edwards BJ, Hellstein JW, Jacobsen PL, Kaltman S, Mariotti A, Migliorati CA, et al. Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy. J Am Dent Assoc 2008;139(12):1674-1677.
72. Cousido MC, Carmona IT, García-Caballero L, Limeres J, Álvarez M, Diz P. In vivo substantivity of 0.12% and 0.2% chlorhexidine mouthrinses on salivary bacteria. Clinical oral investigations 2010;14(4):397-402.
73. Tarassoff P, Csermak K. Avascular necrosis of the jaws: risk factors in metastatic cancer patients. J Oral Maxillofac Surg 2003;61(10):1238-1239.
74. Soltau J, Zirrgiebel U, Esser N, Schaechtele C, Totzke F, Unger C, et al. Antitumor and antiangiogenic efficacy of bisphosphonates in vitro and in a murine RENCA model. Anticancer research 2008;28(2A):933-941.
75. Kyrgidis A, Vahtsevanos K. Risk factors for bisphosphonate-related osteonecrosis of the jaws. Journal of oral and maxillofacial surgery 2009;67(11):2553-2554.
76. Scelza M, Linhares A, Da Silva L, Granjeiro J, Alves G. A multiparametric assay to compare the cytotoxicity of endodontic sealers with primary human osteoblasts. International endodontic journal 2012;45(1):12-18.
77. Debelian G, Olsen I, Tronstad L. Bacteremia in conjunction with endodontic therapy. Dental Traumatology 1995;11(3):142-149.
78. DeLoughery TG. Hemostasis and thrombosis. Springer; 1999.
79. Scully C, Wolff A. Oral surgery in patients on anticoagulant therapy. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 2002;94(1):57-64.
81. Johnson WT, Leary JM. Management of dental patients with bleeding disorders: review and update. Oral Surgery, Oral Medicine, Oral Pathology 1988;66(3):297-303.
82. Shapiro A, McKown C. Oral management of patients with bleeding disorders. Part 1: Medical considerations. Journal (Indiana Dental Association) 1990;70(1):28-31.
83. Chohayeb A. Endodontic therapy in the hemophiliac patient. The New York state dental journal 1981;47(6):326.
84. Debelian GJ, Olsen I, Tronstad L. Systemic diseases caused by oral microorganisms. Dental Traumatology 1994;10(2):57-65.
85. Hülsmann M, Schäfer E. Apical patency: fact and fiction-a myth or a must? A contribution to the discussion. Endo 2009;3:285-307.
86. Murray C, Saunders W. Root canal treatment and general health: a review of the literature. International Endodontic Journal 2000;33(1):1-18.
87. Scully C, Ng YL, Gulabivala K. Systemic complications due to endodontic manipulations. Endodontic Topics 2003;4(1):60-68.
88. McGowan D. Endodontics and infective endocarditis. International endodontic journal 1982;15(3):127-131.
89. Baumgartner JC, Heggers JP, Harrison JW. The incidence of bacteremia related to endodontic procedures I. Nonsurgical endodontics. Journal of endodontics 1976;2(5):135-140.
90. Bender I, Montgomery S. Nonsurgical endodontic procedures for the patient at risk for infective endocarditis and other systemic disorders. Journal of endodontics 1986;12(9):400-407.
91. Seymour R, Lowry R, Whitworth J, Martin M. Infective endocarditis, dentistry and antibiotic prophylaxis; time for a rethink? British dental journal 2000;189(11):610-616.
92. Bender I, Seltzer S, Yermish M. The incidence of bacteremia in endodontic manipulation: preliminary report. Oral Surgery, Oral Medicine, Oral Pathology 1960;13(3):353-360.
93. Fouad AF. Endodontic microbiology. John Wiley & Sons; 2009.
94. Debelian GJ, Olsen I, Tronstad L. Electrophoresis of whole-cell soluble proteins of microorganisms isolated from bacteremia in endodontic therapy. European journal of oral sciences 1996;104(5-6):540-546.
95. Savarrio L, Mackenzie D, Riggio M, Saunders W, Bagg J. Detection of bacteraemias during non-surgicalroot canal treatment. Journal of dentistry 2005;33(4):293-303.
96. Heimdahl A, Hall G, Hedberg M, Sandberg H, Söder P, Tuner K, et al. Detection and quantitation by lysis-filtration of bacteremia after different oral surgical procedures. Journal of Clinical Microbiology 1990;28(10):2205-2209.
97. Bürklein S, Schäfer E. Apically extruded debris with reciprocating single-file and full-sequence rotary instrumentation systems. Journal of endodontics 2012;38(6):850-852.
98. Kirchhoff AL, Fariniuk LF, Mello I. Apical extrusion of debris in flat-oval root canals after using different instrumentation systems. Journal of endodontics 2015;41(2):237-241.
99. Koçak S, Koçak MM, Sağlam BC, Türker SA, Sağsen B, Er Ö. Apical extrusion of debris using self-adjusting file, reciprocating single-file, and 2 rotary instrumentation systems. Journal of endodontics 2013;39(10):1278-1280.
100. Reddy SA, Hicks ML. Apical extrusion of debris using two hand and two rotary instrumentation techniques. Journal of Endodontics 1998;24(3):180-183.
101. Tinaz AC, Alacam T, Uzun O, Maden M, Kayaoglu G. The effect of disruption of apical constriction on periapical extrusion. Journal of endodontics 2005;31(7):533-535.
102. Baumann MA, Beer R. Endodontology. Thieme; 2011.
103. Cruz A, Vera J, Gascón G, Palafox-Sánchez CA, Amezcua O, Mercado G. Debris remaining in the apical third of root canals after chemomechanical preparation by using sodium hypochlorite and Glyde: an in vivo study. Journal of endodontics 2014;40(9):1419-1423.
104. de Melo Ribeiro MV, Silva-Sousa YT, Versiani MA, Lamira A, Steier L, Pécora JD, et al. Comparison of the cleaning efficacy of self-adjusting file and rotary systems in the apical third of oval-shaped canals. Journal of endodontics 2013;39(3):398-401.
105. Haapasalo M, Endal U, Zandi H, Coil JM. Eradication of endodontic infection by instrumentation and irrigation solutions. Endodontic topics 2005;10(1):77-102.
106. Júnior ASA, Cavenago BC, Ordinola-Zapata R, De-Deus G, Bramante CM, Duarte MAH. The effect of larger apical preparations in the danger zone of lower molars prepared using the Mtwo and Reciproc systems. Journal of endodontics 2014;40(11):1855-1859.
107. Olivieri JG, Stöber E, Font MG, González JA, Bragado P, Roig M, et al. In Vitro Comparison in a Manikin Model: Increasing Apical Enlargement with K3 and K3XF Rotary Instruments. Journal of endodontics 2014;40(9):1463-1467.
108. Brunson M, Heilborn C, Johnson DJ, Cohenca N. Effect of apical preparation size and preparation taper on irrigant volume delivered by using negative pressure irrigation system. Journal of endodontics 2010;36(4):721-724.
109. Van Der Sluis L, Shemesh H, Wu M, Wesselink P. An evaluation of the influence of passive ultrasonic irrigation on the seal of root canal fillings. International Endodontic Journal 2007;40(5):356-361.
110. Tan BT, Messer HH. The quality of apical canal preparation using hand and rotary instruments with specific criteria for enlargement based on initial apical file size. Journal of Endodontics 2002;28(9):658-664.
111. Kwok V, Caton JG, Polson AM, Hunter PG. Application of evidence-based dentistry: from research to clinical periodontal practice. Periodontology 2000 2012;59(1):61-74.
112. Miller SA, Forrest JL. Translating evidence-based decision making into practice: appraising and applying the evidence. Journal of Evidence Based Dental Practice 2009;9(4):164-182.
113. Seymour R, Preshaw P, Thomason J, Ellis J, Steele J. Cardiovascular diseases and periodontology. Journal of clinical periodontology 2003;30(4):279-292.
114. Daly B, Batchelor P, Treasure E, Watt R. Essential dental public health. OUP Oxford; 2013.
