TOPIC REVIEW

CALCIUM HYDROXIDE AS A CLINICAL PARADIGM IS SURPASSED BY MINERAL TRIOXIDE AGGREGATE (MTA)

¹ Dentist. Specialist in Comprehensive Dentistry of the Adult. MEd. Sociology of Education. Full Professor-Researcher, School of Dentistry, Universidad de Antioquia. E-mail Address: faluyede@gmail.com

² Dentist. Candidate to the clinical specialization in Comprehensive Dentistry of the Adult with emphasis in Periodontics. Postgraduate Student and Researcher, School of Dentistry, Universidad de Antioquia. E-mail Address: cesarmadrid11@hotmail. com

SUMBITTED: FEBRUARY 14/2012-ACCEPTED: JANUARY 22/2013

Yepes FL and Castrillón CA. Calcium hydroxide as a clinical paradigm is surpassed by mineral trioxide aggregate (MTA). Rev Fac Odontol Univ Antioq 2013; 25(1):. 176-207.

ABSTRACT

INTRODUCTION: as a result of scientific research, calcium hydroxide (CH) enjoyed a privileged position for several decades as a choice with high predictive abilities for pulp therapy. We are now witnessing the collapse of this paradigm due to the emergence of mineral trioxide aggregate (MTA) with its biocompatibility—an ability to stimulate mineralization—, antimicrobial properties, and other advantages that make it more successful in endodontic therapy. The objective of this topic review was to identify the uses of CH and MTA from 1995 to the present, in different clinical conditions. METHODS: this review consisted of a comprehensive literature search in Medline, PubMed, and SciELO from 1995 to the present. It included titles, abstracts, full articles, systematic reviews, and meta-analysis related to CH and MTA. RESULTS: a number of scientific studies highlight the properties of CH in pulp therapy; however, MTA has also been used and studied as a replacement material. CONCLUSIONS: according to research on this field, MTA can be used in the same situations for which CH is recommended, with better probabilities of success.

Key words: pulp therapy, pulp capping, calcium hydroxide, apexification, pulpotomy, mineral trioxide aggregate.

INTRODUCTION

For several decades, scientific research situated calcium hydroxide (CH) in a privileged position as a choice with high predictive abilities for pulp therapy since it allows preserving vitality and stimulating dental tissue remineralization in clinical conditions such as pulp capping, apexification, and internal resorption, to name just a few. However, recent studies on the role of mineral trioxide aggregate (MTA) in pulp therapy claim that this material is challenging the clinical paradigm of CH and is gradually becoming more prevalent due to the good results it offers.

CH is obtained by calcining calcium carbonate: Ca(OH)₂ + CO₂ __ CaCO₃ + H₂O. Moreover, this granular, amorphous, thin powder has distinctive basic properties, such as an alkaline pH of about 12.4, which provides it with a great bactericide power.^{1, 2} When applied on vital pulp, its caustic action produces an area of sterile surface necrosis coupled with hemolysis and albumin coagulation, being attenuated by the formation of a compact underlying layer consisting of calcium carbonate due to the CO₂ produced on tissues and proteins as a result of tooth stimulation.^{1, 2} CH has a density of 2.1; it may be slightly dissolved in water and is insoluble in alcohol. As a distinctive feature, the higher the temperature the lower its solubility.^{1, 3}

The first CH-based medicine was introduced in dentistry by B. W. Hermann in the 1920s and was known as Calxyl.⁴ Since then, CH has been widely used for treating endodontic lesions.

Some of the studies explored during this review examine a material that exhibits CH functions such as MTA, which has become an alternative material as it shows statistically significant differences compared to CH.

MTA was first developed and reported in 1993 by Lee, Torabinejad et al;⁵ its use in dentistry was approved in 1998 by the Food and Drugs Administration and it was commercially launched in 1999 as MTA ProRoot (Dentsply) in gray color until 2002, when its white form entered the market, with the same composition.⁶

This material is a hydrophilic powder that forges in water.⁷ It is composed of tricalcium silicate, tricalcium oxide, silicon oxide, and other mineral oxides that provide it with its properties, such as bismuth oxide, responsible for its radiopacity.^{8, 9} It has a high antimicrobial activity since calcium oxide, when mixed with water, reacts producing CH, which causes an increase in pH by dissociation of calcium ions and hydroxyl, creating an environment that prevents the development of bacteria and fungi.¹⁰

MTA has been internationally used in clinical applications such as apexification, root perforation repairs, retrograde fillings, and direct and indirect pulp capping. It may also be the only material that consistently allows regeneration of periodontal ligament—a cementum-like tissue—and bone formation.¹¹

The goal of this study was to update the CH review previously made by Yepes,¹² since the interest on CH research is still current as this has been the material traditionally used in pulp therapy. MTA was also included in this review because it is gradually replacing CH due to qualities that make of it a better choice; this review reveals that scientific research is witnessing a rupture of a clinical paradigm due to the use of MTA instead of CH.

CLINICAL USES OF CALCIUM HYDROXIDE

Direct pulp capping and pulpotomy

Pulp capping is intended to preserve the vital functions of the pulp in the absence of persistent pain due to external stimuli and when the pulp has been accidently exposed to the oral environment.^{13, 14} Pulp capping and the marginal seal obtained by applying a material on pulp tissue may be the key factor for the final outcome of this procedure.¹⁵ Cox et al¹⁶ showed that the pulp is able to develop a barrier of hard tissue if an adequate biological seal is provided and therefore microorganisms are prevented from reaching pulp tissue. The ideal material for direct pulp capping must be able to control infection, adhere to dentin to prevent microleakage, offer simple clinical management, and promote dentin bridge formation.¹⁷ CH has traditionally been the material of choice as it complies in part with these qualities.¹⁸ However, etching products have shown good performance in preventing microleakage,¹⁹ and their considerable antibacterial effect²⁰ (products containing glutaraldehyde or an acidic property have some antibacterial effects) makes them promising agents for direct pulp capping. Studies on animals have shown that these restorative materials do not cause pulp inflammation or necrosis when directly applied on the exposed pulp if bacteria have been eliminated from the margins.²¹ Some studies suggest that the clinical success of CH ranges from 31 to 100% in pulpotomy.^{22, 23} Other researchers do not mention percentages but describe CH as very successful for pulpotomy.^24-30 The alkaline pH induced by CH not only neutralizes osteoclasts lactic acid, thus preventing dissolution of the dentin's mineral components, but it can also activate alkaline phosphatases, which play an important role in the formation of hard tissue.³¹

Even if local systemic toxicity is absent, bleeding must be controlled in order to allow good contact between drug and pulp tissue.^{23, 32} When bleeding is not controlled, CH is not recommended.

The notions of evidence-based dentistry were used to compare MTA with formocresol (FC), ferric sulfate (FS), and CH as the drugs most commonly used for molar pulpotomy. Current evidence suggests that, in comparison, MTA offers successful clinical and radiographic outcomes significantly higher in all compared periods until exfoliation.³³

Dentin bridge formation

The basic principle of pulp capping is the ability of pulp tissue to repair itself. Several factors affect this process, including age, periodontal status, and stage of root formation, and during the procedure, the main influences are size of the area exposed, its nature (traumatic, mechanical, or bacterial), and microbial contamination of the area, all of which have been considered crucial for pulp capping success.³⁴ The basic pH of CH (pH 12) makes it a good bactericidal agent, and it also allows the formation of a dentin bridge when directly placed on the pulp.²⁵

Studies such as the one by Lu et al,³⁵ which compares the effects of two materials directly placed on the pulp, show that CH at the start of therapy produces mild inflammation which later turns into a superficial necrosis, allowing the formation of dentin bridge, while with the use of a bonding agent (Clearfill SE BOND), the formation of such barrier was significantly lower.

Bleeding control is a procedure that determines the success of direct pulp capping. According to Schroder,³⁶ lack of hemostasis before applying CH affects treatment because clots may form a barrier that prevents contact between the material and the exposed pulp; furthermore, clots may also act as a substrate for microorganisms, leading to pulp infection.³⁷

The fact that MTA hardens in the presence of moisture may allow a better seal, and the results are therefore better in comparison to those obtained with CH; MTA may be used in areas where it is practically impossible to achieve a completely dry environment.³⁸

Pulp capping with MTA produces functional and cytological changes in pulp cells, resulting in the production of reparative dentin on the surface of mechanically exposed pulps. MTA provides pulp cells with a biologically active substrate, which is necessary to control dentinogenic events. The initial effect of MTA on the surface of a mechanically exposed pulp is formation of a layer of crystalline structures. This immediate reaction indicates stimulation of the pulp cells biosynthetic activity by the coating, but it cannot be considered as a direct induction of reparative dentin formation. A new array of non-tubular structures with cell inclusions may be observed under the material within two weeks. Evaluation with scanning electron microscopy shows collagen fibers in direct contact with the surface crystalline layer. Reparative dentinogenesis is evident three weeks after capping, associated with a fibrodentinal matrix. Therefore, MTA is an effective material for direct pulp capping, as it favors the formation of hard tissue bridges during the repair process, if it is performed under aseptic conditions.³⁹

Effects of direct pulp capping (DPC)

Vital pulp therapy is a treatment option intended to preserve the pulp when previously exposed by trauma or decay.

In direct contact with CH, pulp tissue is totally dislocated and destroyed by a caustic effect (a chemical cauterization). This area is known as "obliteration area" consisting of debris, dentin fragments, bleeding, blood clots, blood pigments, and CH particles which form a mummified zone of necrosis due to coagulation and capillary thrombosis. This area, of about 0.2-0.5 mm in thickness, consists of devitalized tissue that has not completely lost its structural architecture and presents little inflammation. The mummified area stimulates the underlying pulp tissue to respond to its full healing potential and to produce dentin bridge.⁴⁰ Basically, tissue healing follows the typical sequence of conjunctive tissue wounds. It implies migration and proliferation of mesenchymal and endothelial pulp cells, as well as collagen formation.⁴¹ When the pulp is protected against irritation, it results in odontoblast differentiation and dentin tissue formation, so the pulp function is normalized.⁴²

A number of materials have been used for direct pulp capping, CH being traditionally accepted as the material of choice because of its proven ability to achieve high success rates. The possibility of using dentin adhesives as pulp coatings is currently under evaluation—but there is some discussion concerning unfavorable results—.⁴³ Another material used for direct pulp capping is MTA, which has been shown to stimulate formation of dentin bridges adjacent to dental pulp. This effect of dentin formation may be connected to sealing strength, alkalinity, biocompatibility, and other remineralizing properties of MTA.⁴⁴

Eskandarizadeh et al⁴⁵ conducted a comparative study on dental pulp response to CH and MTA as pulp capping agents. Based on the results of this study, MTA may be suggested as a material of choice for direct pulp capping.

In a randomized controlled study on human teeth, Leye Benoist et al⁴⁶ compared CH and MTA: the thickness of newly formed dentin was measured at intervals of 3 and 6 months; dentin formation was monitored with radiological measurements through digitized images, using Mesurim Pro® software.

The best results (statistically significant) were observed in the MTA group after 3 months, but after 6 months there were no differences in dentine thickness between the two groups.

Controversies

Some authors claim that CH may degrade during the etching process performed before a restoration, and they think that other materials, such as MTA, may replace it.^{47, 48} Over the past three decades, several studies have been published concerning pulp capping in humans, using CH, binders, and other materials including MTA, which has been evaluated in several studies that have demonstrated its good biocompatibility and sealing properties.⁴⁹

The so-called dentin bridge was first observed when MTA was preliminarily tested in animal models before clinical application in humans;⁵⁰ the results suggest that iatrogenic-based pulp conditions treated with MTA are free of inflammation after 1 week and that a compact dentin bridge forms in less than 3 months, with considerable length and thickness.⁵¹ CH prevents contamination, and few visible defects have been observed, indicating compaction of the hard tissue barrier formed to achieve "good quality" of the bridge.¹⁶

The hard tissue formed under the MTA barrier is probably multifactorial as it involves factors such as sealing ability,^{5, 52, 53} biocompatibility,^{54, 55} and the production of an alkaline environment on the pulp.^56-58 The results of the study by Olsson et al⁵¹ allow to conclude that MTA is clinically easy to use; they also suggest that the pulp experiences less inflammation, and the formation of a hard tissue barrier is more predictable than with CH. Therefore, MTA should be the material of choice for direct pulp capping.⁵¹

As part of this debate, Moretti et al⁵⁹ performed a study in which they evaluated and compared the effects of MTA, CH, and formocresol (FC) as wound dressings after coronal pulp amputation in decayed deciduous molars. In this study, 100% of the teeth treated with FC and MTA were clinically and radiographically evaluated with successful results at all follow-up appointments. In the CH group, internal resorption was radiographically detected in five teeth (35.7 %) during the 3 follow-up months. After six months, six teeth (42.9 %) showed radiographic evidence of failure with resorption, destruction of alveolar bone, and furcation —they also presented radiolucency—; on the other hand, there is still some controversy on its application in deciduous teeth pulpotomy due to the possibility of internal resorption.²³

Indirect pulp capping (IPC)

Indirect pulp capping (IPC) is a technique still studied by many authors. Fagundes et al,⁶⁰ for example, reported a case in which CH was successfully used to preserve pulp vitality of a decayed permanent molar in a 16-year-old patient who was monitored for four years. It should be added that there is a direct relation between the degree of cytotoxicity of a given material and the success of these procedures; for that reason, Modena et al⁶¹ conducted a study to demonstrate that CH is the material of choice when seeking greater biocompatibility and less cytotoxicity, as it is better than adhesive systems, resins, and glass ionomer cements.^{62, 63} These authors do not mention MTA, which has been proven to have biocompatibility with human tissue.

As referenced in the literature, both in vitro and in vivo studies have demonstrated that MTA is the most suitable material for direct or indirect pulp capping due to its excellent pulp sealing ability and its biocompatibility (which prevents toxicity and tissue irritability), as well as cell induction, cell proliferation, cementum regeneration, and dentin bridge formation.^64-66

Biological basis of the dentin-pulp complex clinical response

CH has been widely used to induce dentin regeneration by means of dentinal bridge formation in areas where the pulp is exposed due to dental tissue injury; however, the biological processes underlying such events are unclear. Graham et al, ⁶⁷ in their study on the effect of CH in solubilization of the dentin matrix bioactive components involved in dentin bridge formation, provide a rational explanation for the action of CH during pulp capping, in which cellular activity may be mediated by release of growth factors such as BMP, TGFbeta1, collagen alpha-1, and the expression of genes and other bioactive molecules from dentin and CH.

In the presence of moisture, the MTA dissociates into a gel of calcium silicate hydrate which may explain the clinical success of this material in the biological processes of pulp repair.⁵⁶ Furthermore, the process of dentin repair may be related to a physical-chemical reaction occurring between MTA and the tooth as described by Sarkar et al.⁶⁵ According to these authors, MTA is a bioactive material which, when in contact with the dentin, produces hydroxyapatite composites at the tooth/ material interface.

Endodontic filling with calcium hydroxide

A variety of root canal sealers have been recommended for this purpose, in combination with fillers. These materials must have satisfactory physical-chemical properties as well as biocompatibility. Studies of the cytotoxic and long-term biocompatibility of three types of sealants (resin-based, eugenol-zinc oxide, and CH) in human periodontal ligament have shown that CH-based sealants offer a more favorable response to periradicular tissues.⁶⁸ The genotoxicity of these materials was evaluated by Huang et al⁶⁹ through an electrophoresis study.

The results were obtained by analysis of variance to compare the different filling materials. The highest level of DNA damage was induced by resin-based materials; the eugenol-zinc oxide filler did not always lead to an increase in genotoxicity, but this effect was not evidenced with the CH-based material (Sealapex).

The effect of CH as a root canal sealant has been described in vitro. In order to associate CH with teeth microtensile fracture toughness (MFT), a total of 40 extracted healthy permanent upper incisors were prepared with rotary instruments and filled with CH. The teeth were stored in a moist environment for 7, 28, and 84 days. As a control group, 10 teeth were filled with gutta-percha alone. As a result, the researchers noted that filling with CH facilitates teeth MFT in 13.9 Mpa after 77 days. Weakening of dentin from 23 to 43.9% after sealing with CH provides convincing evidence to reconsider the use of this material in endodontic therapy.⁷⁰ This means that root canal filling with CH weakens teeth after a period of 70 days.^{71, 72}

Controversies

According to studies by Rosenberg et al,⁷⁰ CH is not a good material for root canal filling; however, in an in vitro study, Huang et al⁶⁸ demonstrated the cytotoxicity of three different root canal sealers in human periodontal ligament: a resin-base sealer (AH26 and AHPlus), an eugenol-zinc oxide sealer (Canals, Endomethansone and N2) and a CH-based sealer (Sealapex). Their results proved that root canal fillers constantly dissolve when exposed to an aqueous environment for extended periods of time, which may cause cytotoxic reactions. The CHbased material offered a more favorable response to periradicular tissues. Other authors⁷³ state that other drugs may have a greater potential than CH, such as camphor paramonochlorophenol, corticosteroids, antibiotics, and antibiotic-corticosteroid compounds.

Bactericidal effect

CH is still used as a disinfectant agent in endodontics. Root canal infection is rich in anaerobic bacteria, which use tissue debris and serum proteins as nutrients. Several studies have shown higher success rates when root canals are free of bacteria when sealed.⁷⁴

CH is recommended as the drug of choice for treating root canal infection. Its antimicrobial mechanism of action is influenced by the rate of dissociation of calcium ions and hydroxyl ions in a high pH environment, which inhibits enzymatic activity—essential for microbial life, that is to say, for metabolism, cell growth, and cell division—.^{75, 76} The lethal effects of CH in bacterial cells are probably due to protein denaturation, as well as to damage to DNA and cytoplasmic membranes.⁷⁷

It has been recently shown that mechanical preparation alone does not guarantee full healing, so a drug is also needed.⁷⁸ Microorganism elimination is not always uniform due to different vulnerability levels of the species involved.⁷⁹ Pigmented gramnegative anaerobic bacteria such as Porphyromonas gingivalis have been linked to the signs and symptoms of infected teeth. However, facultative microorganisms such as Enterococus faecalis, Actinomyces spp. and even Candida albicans are considered by many to be the most resistant species in the oral cavity, and a possible cause of endodontic treatment failure.^{80, 81} Microorganisms and their products may spread the infection from the root canal through several routes, including the apical foramen as well as lateral and accessory canals, promoting adjacent periodontal lesions.⁸²

For an antimicrobial agent to be effective, it must act not only in the root canal but also up to a certain distance, in the dentinal tubules, and ideally it should reach the root's outer surface.⁸³

CH is an excellent antimicrobial drug; however, a number of associating vehicles have been suggested in order to improve its properties. As a certain period of time is required for effective destruction of bacteria by direct contact with the root canal and indirect contact with dentinal tubules, the vehicle's solubility is more important than its antimicrobial effect so that it works in a synergistic manner and rapidly spreads reaching those lateral canals that are inaccessible by mechanical preparation, thereby improving the natural antimicrobial property of CH. The greater the rate of dissociation and diffusion of hydroxyl ions from CH paste the greater its antimicrobial effect—and this is achieved with soluble vehicles.⁷⁶

Among the substances used as CH vehicles are distilled water, saline solution, and glycerin. Recently, chlorhexidine has proven to be an effective chemical disinfectant;⁸⁴ due to its antimicrobial action and its adsorption to hard tissues with gradual and constant release at therapeutic levels,^85-89 it has been recommended as an intracanal medication.

Candida albicans and Enterococcus faecalis have proved resistant to the antimicrobial action of CH, but they are sensitive to chlorhexidine gluconate. In an in vitro study, Ballal et al⁹⁰ examined the antimicrobial effect of CH paste, 2% chlorhexidine gel, and their combination against Candida albicans and Enterococcus faecalis, concluding that in avoiding root canal treatment failures, 2% chlorhexidine gel may be more effective than CH paste.

In determining the vehicle's influence⁹¹ on the antimicrobial action of CH, Estrela et al concluded that, under the conditions of their study,⁹² the various vehicles related with CH pastes did not influence the time required for microbial inactivation.

Although in vivo studies have concluded that CH is the most effective intracanal medication,⁹³ other studies have shown that potassium iodide (KI) and chlorhexidine (CHN) are effective against CH-resistant bacteria, thus complementing the antibacterial activity of CH.^94-98 CH preparations with KI or CHN may therefore be one way to improve the efficacy of intracanal treatment.

Evans et al¹⁰⁰ conducted an in vitro study to assess the antibacterial effect of CH-KI and CH-CHN combinations against E. faecalis.⁷³ Their findings showed the benefits of combining CH with either KI or CHN.

The widespread use of CH is largely due to its long lasting alkalinity and its ability to stop the provision of nutrients to residual bacteria. These properties were not affected by the addition of CHN or KI, which clearly increased the medication's antibacterial effect.⁹⁸

Actinomyces israelii has been constantly cited as a cause of endodontic treatment failure. Barnard et al¹⁰¹ studied the antimicrobial effect of this important pathogen, with medicines normally used in root canal cleaning such as sodium hypochlorite and CH. They found out that both 1% sodium hypochlorite and CH are very effective in the elimination of A. israelii as a planktonic microorganism.

Used as an intracanal medication, CH is an excellent antimicrobial because it controls infection in the root canal system of necrotic teeth and promotes periapical repair.¹⁰² Similarly, CHresistant microorganisms such as E. faecalis are sensitive to the action of chlorhexidine gluconate in its planktonic state.¹⁰³ The correct selection of antimicrobial agents as medication between appointments is as important as root canal instrumentation and irrigation to remove etiologic pathogens. Among the different medications available, CH is perhaps the most widely used;^104-107 its antibacterial effect is mainly due to the release of free radicals (hydroxyl)¹⁰⁵ and to its permanent basic pH.^{108, 109} Some researchers have found viable bacteria within the dentinal tubules, even after long periods of treatment with CH.^{95, 110} Interestingly enough, Haapasalo et al¹¹¹ found out that the antimicrobial effect of CH could be neutralized in vitro by dentine powder.

Tang et al¹¹² evaluated residual microorganisms after conventional endodontic treatment, by using medicines such as Septomixine or CH and found out that neither could effectively inhibit residual bacterial growth in canals during appointment intervals. More research is needed to determine the most appropriate medication for root canal infections.¹¹³

Soriano et al¹¹⁴ recommend a limited use of CH in conventional endodontic therapy, because it does not eliminate the entire spectrum of microorganisms associated with pulp necrosis. In these cases, the most common species are: F. nucleatum spp. Borriela vicentii, C. sputigena, C. ochracea, S. constellatus, V. parvula, P. gingivalis, P. melaninogenica and S. sanguis. Most microorganisms were reduced after treatment, especially A. gerencseriae, A. israelii, A. naeslundii, C. gingivalis, C. ochracea, P. gingivalis, S. noxia, sanguis and S. oral. On the contrary, A. actinomycetemcomitans, C. sputigena and E. corrodens, increased in number after CH therapy. CH has a wide range of antimicrobial activity against common endodontic pathogens, but it is less effective against Enterococcus faecalis and Candida albicans. In addition, its effect on microbial biofilms is also controversial.

The common belief that endodontic treatment of necrotic teeth should be done in several appointments because by then bacteria have grown and spread throughout the canal system^115-117 suggests that it is impossible to fully disinfect the root canal system in a single session and therefore it is necessary to use intracanal medications with CH in order to remove the bacteria that was not removed during biomechanical preparation.^{102, 118}

Nevertheless, some studies report that, even using CH, complete root canal disinfection is not achieved, and even 7 days after it has been placed, there is a possibility of bacterial recolonization at similar levels to those that existed before canal instrumentation. ^{93, 107, 119} Caviedes et al¹²⁰ published a review of the evidence available in the scientific literature about the effectiveness of endodontic therapy in a single appointment, based on both the incidence of exacerbations and long-term periapical repair; they concluded that all teeth may be adequately treated in one session regardless of pulp and periapical status. However, the number of canals, the time available and the operator skills are factors that may hinder the completion of treatment in one session.

Many studies^{92, 103, 105} claim that CH has lethal effects on bacteria. However, these studies were performed in vitro and in direct contact with bacteria, a condition that is not generally possible within the root canal system due to its complex anatomy. Another aspect to be highlighted is failure of CH to kill bacteria inside the dentinal tubules.¹²¹

It has been reported that several CH preparations are unable to eliminate E. faecalis inside the dentinal tubules even if it is located at the tubules entrance..^{122, 123}

For CH to be effective in removing bacteria from the dentinal tubules, the hydroxyl ions must diffuse into the dentin in high concentrations. It has been reported that the high surface tension of CH prevents it from entering the dentinal tubules. For this reason, several attempts have been made to mix CH with a number of vehicles for two basic purposes: to modify surface tension and to prolong ionic release.^124-127 It has been reported that the anesthetic solution is the most favorable agent to reduce CH surface tension.¹²⁸

Induction of hard tissue

Due to the ability of CH to form dentinal bridges, it has been used to induce apical closure in immature teeth and to repair perforations. Recent studies have shown that MTA also has this ability.

Treatment of fractured teeth and perforations

CH has been included in compounds used for treating perforations, fractures, and root resorption; these compounds also play an important role in dental trauma following avulsion and luxations¹¹⁶ The problem with this method is dentin weakening caused by CH, resulting in possible fractures of the cervical third of the root.^129-131 CH has demonstrated an ability to induce hard tissue in apexification and root fractures, and it also has an effect on infectionrelated external resorption.^132-136 An ideal material should be able to seal the communication passages within the root canal system, the perforation, the fracture, and their surrounding tissues; it should not be toxic or carcinogenic and must be biocompatible, insoluble in tissue fluids, and dimensionally stable. MTA was initially recommended for having these "ideal" features; it has also been recommended for pulp capping, pulpotomy, apical barrier formation in teeth with open apexes, perforations repair, and root canal filling.¹³¹

In a laboratory study, Hakki et al¹³² analyzed the response of periodontal ligament fibroblasts (PLF) of root perforations restored with materials as varied as amalgam, Dyract, IRM, Super Bond C and B, and MTA. Electron microscopy revealed that the group of perforations treated with MTA presented the largest population of viable cells compared to the other materials.

Root fractures are common. Vertical and horizontal fractures should be treated differently, as well as their diagnosis and prognosis. Among the causes of vertical fractures are iatrogenesis (canal overwork, excessive compaction during condensation, placing posts with spaces or without good crownroot ratio), physical trauma, and bruxism, to name just a few. Fractures are handled as apexifications, but they require crown diagnosis. Vertical fractures usually have a poor prognosis. In the case of horizontal fractures, the prognosis depends on the level at which the fracture happens.

Apexification

Dental trauma in teeth with incomplete root formation may cause pulp necrosis, interruption of root formation, and the subsequent development of periapical lesions.

Its treatment may include induction of apical closure through the application of intracanal biomaterials to induce periapical repair in a procedure called apexification.¹³³

In apexification, through chemical-mechanical debridement and periodical maintenance, CH used to be the material of choice for biological sealing of wide foramen openings, although sometimes this was not achieved.^{134, 137, 138} Now this can be done with MTA in a single appointment.

Çaliskan et al¹³⁹ reported a case of a maxillary central incisor with a widely open apex and a large periapical lesion as a result of pulp necrosis due to trauma suffered 12 years before. After treatment with CH overall success was achieved in 15 months. In another study by Vellore,¹³⁸ the author emphasized the benefits still offered by CH in pulpless teeth with open apex.

Mohammadi et al⁷⁷ reported the many benefits of CH in apexification, with greater success in longterm treatments due to its antimicrobial properties and its ability to stimulate new bone formation.

Apexification treatments generally last for one year or more. It has been shown that these teeth are prone to fracture and may be lost before or after a long period of apexification with CH.¹⁴⁰ Chala et al¹⁴¹ conducted a quantitative systematic review to compare the efficacy of MTA and CH during the endodontic treatment of immature permanent teeth. As a result, they found out that both materials can be used..

Controversies

It has been reported that CH is successful in inducing apical closure in a large number of formulations, linking apical closure with the long-term antibacterial effect of CH, since it has been observed that calcified tissue forms in the absence of microorganisms.¹⁴²

It has also been noted that the material's alkalinity may act as acidic buffer to inflammatory reactions, favoring bone remodeling since they neutralize the acids produced by osteoclasts and macrophages.¹⁴³ In this regard, it is important to note that it is unlikely that calcium released by CH dissociation can be used in the formation of an apical barrier, since it is a very unstable ion, and in order to be useful in the formation of this calcified tissue it needs a constant supply of calcium, which may come through blood.¹⁴² Finally, it is also been reported that the remnants of Hertwig's epithelial root sheath that remain intact may favor apical closure.¹⁴⁴

Meligy et al¹⁴⁵ conducted a clinical and radiographic study to compare two materials used to induce root seal of permanent teeth with pulp necrosis and immature apices (apexification): MTA and CH. Follow-up evaluations revealed failure due to persistent periradicular inflammation and pain on percussion at 6 and 12 months postoperative evaluation in 2 teeth treated with CH. The remaining 13 teeth showed clinical and radiographic success after 12 months of intervention. None of the teeth treated with MTA showed clinical or radiographic pathology. This study concluded that MTA is a suitable replacement for the CH in apexification procedures.

Electron microscopy studies suggest that MTA's physical properties are essential to treatment success.¹⁴⁶ Nair et al¹⁴⁷ demonstrated that MTA offers easier clinical application and is successful in vital pulp therapy procedures in both animals^{148, 149} and humans.^150-154 MTA has better seal abilities than amalgam and eugenol-zinc oxide.^{152, 155, 156} Furthermore, its ability to stimulate cytokine release from bone tissue cells has been demonstrated, which suggests that it actively promotes hard tissue formation.¹⁵²

Torabinejad et al¹⁵⁵ argue that CH dissociates into two ions with exactly the opposite effects, since while the Ca⁺⁺ ion stimulates cell proliferation the OH^- ion suppresses cell activity and interrupts the pulp's vital processes. This suggests that it is not CH the one that actually stimulates dentin bridge formation, but rather that the pulp tissue potential to repair itself seeks protection against the chemical damage to which it is subjected.^{157, 158}

Internal and external root resorption

Inflammatory root resorption remains one of the most common complications of dental trauma. With the recent emergence of materials that are not only biocompatible but also bio-inductive, the idea of simple conservation is shifting towards an emphasis on residual pulp tissue regeneration—MTA being a material with tremendous potential for regeneration—.⁹ Güzeler et al¹⁵⁹ described the benefits of MTA in the treatment of fractured immature teeth with periapical lesions, observing resorption interruption, complete healing of the periapical area, and restoration of periodontal ligament space in follow-up periods of 12 and 24 months. When dealing with external resorption resulting from avulsions, MTA is usually the material of choice as it offers greater efficiency compared to CH;¹⁵⁹ however, other authors still support its use as complement for handling internal and external resorptions.^161-163

Controversies

For CH to achieve the aforementioned effects, it must have a high degree of diffusion to the periapex and the dentin's outer layer by penetrating through the dentinal tubules—something that is improbable due to the high reactivity of the OHions, the dentine buffer system, and its high surface tension.^{125, 164-167}

According to several studies,^{163, 168-171} CH is the material of choice for root resorption treatment when used as an intracanal medication, since its high pH has the ability to kill bacteria while at the same time altering the local environment of resorption sites on the root surface through the dentinal tubules. However, it has been discussed that changing the pH with a CH intracanal medication is hard to achieve, particularly in an external resorption process where root surface pH has been calculated to be 4.5.

For some authors, apexification with CH is still a good alternative treatment but the current general consensus recommends using MTA.^{141, 146}

CH as a desensitizing agent

Tooth sensitivity is a common clinical condition. It is defined as pain caused by dentin exposure in response to thermal, chemical, tactile, or osmotic stimuli. In some people it is due to anomalies in dental tissue development, when cement and enamel are not covering the dentin as they normally should.

In general, dentin hypersensitivity is multifactorial.¹⁷¹ Regardless of the etiology of dentin exposure, a feature that seems to be common is the exposure of dentinal tubules—which serve as a direct connection between the external environment and dental pulp— . If the tubules are not exposed, it seems unlikely for sensitivity to occur, so once it is established, the pulp may be irreversibly sensitive. The treatment is therefore not only aimed at restoring the tubules' original impermeability but also to control neural elements inside the pulp to avoid external stimulant effects.^{173, 174}

Dental hypersensitivity is commonly treated with coatings, anti-inflammatories, tubular sealing procedures, or restoration resins.¹⁷⁵ Several non-invasive, reversible systems have been recommended to treat this condition based on their ability to occlude dentinal tubules. Two methods used for closing the dentinal tubules are the application of either a CH suspension^{176, 177} or a glutaraldehyde-based primer (GDP).

Dental hypersensitivity after grinding for a full crown is characterized by pain resulting from the transmission of stimuli through the exposed dentin, that is, by a hydrodynamic mechanism.¹⁷⁸ Moreover, loss or maladjustment of temporary restorations is common,¹⁷⁹ and microorganisms may penetrate the dentinal tubules causing pain or even pulp disease.¹⁸⁰ In an in vivo study, Wolfart et al¹⁸¹ evaluated the effect of a CH suspension in reducing tooth sensitivity and concluded that it does occur. It is important to clarify that using CH to desensitize teeth after grinding does not alter the results of the final restoration.^{182, 183} Pashley et al¹⁸⁴ demonstrated the desensitizing effect of CH to seal dentin surface and to reduce by 48% the tubular permeability in comparison with an untreated dentin. CH is recommended for teeth that remain sensitive after preparation of a full crown.^{185, 186} It has been demonstrated that CH paste has a good desensitizing effect on hypersensitive root surfaces.^187-189

In their topic reviews, Bartold¹⁸⁹ and McFall¹⁹⁰ mention several studies that refer to the effectiveness of covering dentinal tubules with CH to eliminate tooth sensitivity. However, Scherman and Jacobsen¹⁹¹ point out that CH may irritate gingival tissue. It is important to note that most of the studies that report pH changes in the dentin outer layer and the periapical area are in vitro studies performed on extracted teeth, where the dentin buffer system may be altered and OH^- ions may not be able to react, thereby reducing the barriers to spread through the root canal system.^191-193

Controversies

There is a large variety of products for treating sensitivity; some appear to be more effective than others and some can even be applied at home, such as stannous fluoride, sodium fluoride, monofluorophosphate, and strontium chloride which have been extensively studied and have shown to be effective. In this sense CH is in disadvantage because it must be applied at the dentist's office.

Caviedes et al concluded¹⁹⁴ that CH has been the material most widely used in current endodontics; however, its mechanism of action is not well supported. Its high surface tension and its poor ability to dissolve tissue prevent it from being a good candidate for irrigation during conventional endodontic therapy. It should also be noted that MTA is gradually breaking the paradigm of the predominant clinical use of CH in pulp therapy.

CONCLUSIONS

During the last two decades, MTA began to take the place of CH in the treatment of a variety of pulp-related conditions. The main reasons for this replacement has been the delayed effect of CH to stimulate hard tissue formation, the quality of hard tissue formed, and the dentin weakening effect, which in some cases leads to fractures in immature teeth.

For many decades, CH has been the material of choice in pulp capping, pulpotomy, teeth with incomplete root formation (apexogenesis), and pulp necrosis (apexification). It has also played an important role in teeth with root fractures and pulp necrosis at the coronal area, as well as in teeth with infection related to external root resorption.¹³³ Despite its success in many of the aforementioned complications, a number of deficiencies have been observed, and several studies have demonstrated better results with MTA, although CH is still used.

The studies included in this topic review may lead to the conclusion that it is now the time to replace CH by MTA in situations such as pulp capping, pulpotomy, apexogenesis, perforations, and apexification. Before reaching a conclusion in that regard, it is necessary to review new studies of different methods with long-term results. The studies analyzed this time provide MTA with serious scientific support.

REFERENCES