Effect of Remineralizing Agents on the Prevention of Enamel Erosion: A Systematic Review

ISSN - 1519-0501 DOI: 10.4034/PBOCI.2014.141.09 Effect of Remineralizing Agents on the Prevention of Enamel Erosion: A Systematic Review Fabíola Galbiatti de Carvalho 1, Bruno Firmino de Oliveira 2, Hugo Lemes Carlo 1, Rogério Lacerda dos Santos 2, Gymenna Maria Tenório Guenês 2, Ricardo Dias de Castro 1 1 Department of Clinic and Social Dentistry, Center of Health Sciences of Federal University of Paraiba, Brazil. 2 School of Dentistry, Federal University of Campina Grande, Patos, Brazil. ABSTRACT Introduction: Due to the increasing prevalence of dental erosion in the last years, it is relevant to evaluate the potential of different remineralizing agents to prevent this dental alteration. Objective: To perform a systematic literature review to investigate whether products containing casein phosphopeptide amorphous calcium phosphate (CPP-) remineralizing agents are effective in preventing enamel erosion in order to provide information to health professionals who deal with patients at risk of erosion. Materials and Methods: A search was performed in the PUBMED database for scientific studies in journals published in English from January 01, 2003 to March 30, 2012. A total of 230 articles were found and 32 of these were selected. Results: All fluoride agents (dentifrices, fluoride gels, varnishes and ) were effective in preventing erosion and the higher the concentration and lower the ph of agents, the greater their prevention. Although several fluoride compounds have been investigated, titanium tetrafluoride has shown the greatest protection against erosion, regardless of the agent. With respect to CPP- agents, these were effective in preventing after erosive challenge. Conclusions: The majority of studies were conducted in vitro. The composition, fluoride concentration and ph of remineralizing agents have influenced the effectiveness in preventing enamel erosion. It is important to conduct in vivo studies and clinical protocols for the application of products against erosion. Key-words: Tooth erosion; Fluoride; Dental enamel. INTRODUCTION Dental caries has shown a decline in prevalence in recent years due to the use of fluoride products and education and prevention dental programs [1]. However, the lifestyle and eating habits of modern society have contributed to the onset of disorders other than dental caries such as erosion [2]. Dental erosion is an irreversible loss of tooth structure by chemical processes of dissolution without bacterial involvement [2-6]. These s introduced into the oral cavity may have intrinsic ( from the stomach by gastroesophageal disorders) and extrinsic origin (diet and other contaminants) [1-4]. Studies have shown that ic drinks are the agents most related with the occurrence of dental erosion due to their frequent contact with dental structures by dietary habits of the population [5-7]. The degree of demineralization of tooth structure caused by erosion depends primarily on the amount and frequency of the consumption of ic drinks, type of and the way these drinks are ingested [2]. To prevent the occurrence of tooth erosion, resources for guidance regarding diet may be used, as well as the application of products that minimize demineralization and promote remineralization of the tooth structure [2]. Diet changes in family habits already established become complex [2]. Thus, the association of diet advice with the use of remineralizing agents is a therapy used to prevent erosion. The remineralizing agent most widely used is sodium fluoride (NaF) present in s, mouthwashes, gels and varnishes [8-10]. Besides NaF, other compounds containing polyvalent metal ions such as titanium tetrafluoride (TiF 4 ), stannous fluoride (SnF 2 ) and amine fluoride (AmF), as well as CPP--containing products (casein phosphopeptide - CPP and amorphous calcium phosphate - ) have been investigated [11-16]. The CPP- complex has the aim of providing an additional source of calcium and phosphate ions to the oral environment and act in the remineralization of the tooth structure after the demineralization cycle due to dental caries or erosion [11,12]. Although the preventive action of fluoride against dental caries long be based on literature, its role in dental erosion is still controversial, since calcium fluoride (CaF 2 ) formed on the tooth surface can be dissolved by most s of erosive drinks [1]. Furthermore, the knowledge of the effectiveness of Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64 55

various agents in the prevention of dental erosion (gel, varnish, fluoride s and CPP--containing products) becomes important for all professionals who deal with these patients, especially dentists, nutritionists and physicians. Thus, the aim of this study was to analyze by means of systematic review from January 1, 2003 to March 30, 2012, the effectiveness of fluoride agents (, gel, varnish and ) and CPP-containing agents in preventing the development of dental enamel erosion. MATERIAL AND METHODS For the development of this review study, a search of scientific studies in the Medline-PubMed databases was made using the key words "tooth erosion and fluoride" and "tooth erosion and CPP-", published in international journals in English between January 1, 2003 and March 20, 2012. This period was chosen due to the information that in Brazil, the consumption of soft drinks increased by 490 % from 1995 to 2003 [17]. Thus, the authors aimed to investigate the studies on enamel erosion prevention with remineralizing agents from the year 2003. The selected studies were identified from the titles and abstracts by two reviewers, using the words "tooth erosion and fluoride" and "tooth erosion and CPP- " considering the following inclusion criteria: studies in English published in Pubmed; development of enamel erosion and in vitro, in situ and in vivo research studies. In cases where it was not possible to verify the inclusion criteria from the abstract, the articles were obtained and read in full. Exclusion criteria were articles on literature review, dentin erosion, abrasion associated erosion, erosion on dental materials, association of erosion to laser treatment, bleaching agents, desensitizing, biofilm inhibition, antimicrobial products (xylitol and triclosan), dentin sensitivity, metalloproteinase and other non-carious cervical lesions; ic drinks with added calcium or CPP-; development of erosion by herbal, ph assessment on drinks or, erosion of saliva substitutes, studies on diagnosis, prevalence and treatment of erosion and associated systemic changes and structural evaluation of the enamel after erosion. Overall, 230 articles were found, of these 32 were selected. With the words "tooth erosion and fluoride" 203 articles were found and 23 were selected. Likewise, with the words "tooth erosion and CPP-" 28 articles were found and 9 were selected. Tables 1 and 2 show how many articles were removed according to each exclusion criterion using the search keywords. After selected, the 32 articles were read by two reviewers. Disagreements were resolved by discussion between researchers to reach a consensus. The relevant information was compiled into tables with the following information from each article: author (s) year; study type (in vitro, in situ, in vivo), sample size; fluoride agent and / or CPP- (involving fluoride concentration); erosive agent (type of, ph, exposure time); study analysis and main findings. Table 1. Distribution of articles not included in this systematic review according to the exclusion criteria with words "tooth erosion and fluoride". Exclusion criteria with words "tooth erosion and fluoride" Number of articles Literature review 32 Dentin erosion 30 Association of erosion and abrasion 27 Association of laser and erosion 14 Association of desensitizing s and erosion 11 Studies on erosion diagnosis, prevalence and treatment 11 Evaluation of ph on drinks or 10 Development of erosion by drinks added of calcium, casein or CPP- 9 Structural assessment of enamel after erosion 8 Association of erosion with systemic disorders 6 Erosion on dental materials 4 Association of bleaching agents and erosion 3 Association of Antimicrobial Products ( xylitol and triclosan) and erosion 3 Development of erosion by saliva substitutes 3 Association of biofilm control and erosion 2 Association of metalloproteinase and erosion 2 Association of dentinal sensitivity and erosion 2 Association with other non- carious cervical lesions 1 Development of erosion by herbal 1 No abstract 1 56 Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64

Table 2. Distribution of articles not included in this systematic review according to the exclusion criteria and words tooth erosion and CPP-. Exclusion criteria with words "tooth erosion and CPP-" Number of articles Literature review 6 Dentin erosion 2 Association of erosion and abrasion 2 Association of desensitizing s and erosion 2 Studies on erosion diagnosis, prevalence and treatment 2 Development of erosion by drinks added of casein or CPP- 2 Erosion on dental materials 1 Association of bleaching agents and erosion 1 Association of biofilm control and erosion 1 RESULTS Overall, 32 original research studies addressing the prevention and control of the development of dental enamel erosion with fluoride and CPP--containing agents were selected. Tables 3 and 4 show data collected for each item evaluated in this study. In vitro studies were the most commonly found (84.4% studies) (Tables 3 and 4). The enamels used in the investigations of studies were 30.3 % bovine incisors, 30.3 % human molars, 27.3 % 3 rd molars, 9 % permanent incisors and 3 % premolars. The main types of analysis were related to the assessment of and the tests most widely used were profilometry and surface microhardness (33.3 % and 22.2 % of tests, respectively) and the main erosive agents used were citric with different ph (from 2.1 to 3.8) (34.7 % of studies) and cola drink (28.1 % of studies) (Tables 3 and 4). Overall, 23 articles related to the effect of fluoride agents (dentifrice, gels, and varnish) on the prevention of the development of enamel erosion were described in Table 3. Twelve studies evaluated the effect of fluoride, five studies evaluated the effect of fluoride s, gels were investigated in one study and two studies assessed the effect of varnishes. Only three studies compared gels, and varnishes, and no study compared the four agents. Among studies comparing agents, fluoride varnish (especially those containing TiF 4 ) showed better results in prevention against enamel erosion, followed by gels and fluoride (Table 3). Various fluoride compounds such as NaF, SnF 2, TiF 4, AmF, zirconium tetrafluoride (ZrF 4 ), hafnium tetrafluoride (HfF 4 ), zinc fluoride (ZnF 2 ) and stannous chloride (SnCl 2 ) were investigated. According to the studies evaluated, when these compounds were compared for their protective effect on the development of enamel erosion, 15.7% of studies showed that TiF 4 provided the highest protection, followed by SnF 2 (12.5 % of studies) and AmF (9.3% of studies), regardless of the fluoride agent in which the compounds were added (Table 3). NaF showed lower protection against erosion compared to TiF 4, SnF 2 and AmF. The other compounds were tested in only two studies, not allowing comparisons (Table 3). The fluoride compound most widely used in s was NaF (71.4 % of studies) and the best results of efficacy against erosion were found with higher fluoride concentrations (1150 and 1450 ppm fluoride). Two studies have shown that the use of s containing SnF 2 promoted greater reduction compared to NaF. Regardless of the fluoride compound, it was also found that the higher the fluoride agent concentration and lower the ph of, the higher the enamel erosion inhibition (Table 3). However, five studies showed that TiF 4, AmF and SnF 2 showed lower compared to NaF. Only one article compared fluoride gels with agents and fluoride; AmF fluoride gel had lower than CPP-. Nine articles on the effect of CPP-containing products for preventing the development of enamel erosion are described in Table 4. Five studies evaluated the effect of s, one study evaluated with different concentrations and four studies evaluated the effect of mousses. No study compared the three types of agents. In all studies, regardless of agent type, CPP- was effective in protecting demineralization and after erosive challenges. DISCUSSION Many strategies have been used to prevent dental erosion such as dietary control and use of products that remineralize the tooth structure. The use of fluoride agents in the prevention of dental erosion is more widespread than CPP- agents because the latter are relatively new on domestic and international markets. Thus, the number of studies with CPP-containing products and dental erosion is smaller compared to fluoride. Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64 57

Table 3. Studies on fluoride agents in the prevention and control of dental enamel erosion in the period from 2003 to 2012. Author Year Study Sample Fluoride Agent Erosive Agent Study Analysis Results Hughes et al. [27] 2004 in vitro n = 5 for each group (3 rd Aquafresh Macleans, Sensitive, Colgate Total, Plax, Endekay, FluoriGuard and Acidulated gel orange juice (ph=2.91 and 3.4), currant drink (ph=2.7 and 5.53), and citric (ph=2.15) fluoride added to ic, or present in fluorinated products and used as a pre-treatment reduced the enamel erosion. Vieira et al. [25] 2005 in vitro n = 5 for each group (bovine incisors ) gel : 1 % TiF 4 ; 4%TiF 4, 1% AmF and 0:25 %, AmF solution 0.1% difluorosilane fluoride varnish citric (ph = 3) (atomic absorption spectroscopy) only fluoride varnish prevented, showing a protective effect on the development of dental erosion. Hove et al. [14] 2006 in vitro n = 3 for each group molars ) Fluoride of TiF 4, SnF 2 and NaF (ph = 2) depth of mineral loss (white light interferometry) TiF4 reduced depth by 88%, while SnF2 reduced depth by 50% and NaF by 25%. Lennon et al. [32] Newby et al. [21] 2006 in vitro n = 12 for (bovine incisors ) 2006 in vitro n = 10 for molars ) NaF gel (250 ppm F) and AmF (12,500 ppm F), CPP + Fluoride (250ppm F ) s containing 1100, 1150 and 1450 ppm F citric (ph = 2.3) citric (ph = 3.8) (profilometry ) AmF protected against erosion, but casein + fluoride and NaF provided little protection. The s increased protection against erosion. The concentration of 1450 ppm F showed the best results. Young et al. [15] 2006 in vivo 6 subjects for s containing NaF or SnF 2 citric (ph = 2.2 and 2.7) (atomic absorption spectroscopy ) only SnF 2 reduced. Hove et al. [16] 2007 in vitro n = 3 for each group TiF 4, SnF 2 and NaF (ph = 2.2) surface roughness (white light interferometry) TiF 4 showed the best results with lowest roughness. NaF showed no significant protective effect against erosion. Magalhães et al. [33] 2007 in vitro n = 15 for (bovine fluoride varnish Duraphat (NaF, 2.26%F ), Duofluorid (NaF, 2.71 % F), TiF 4 (2.45 % F ) Cola soft drink (ph = 2.9) surface roughness and (profilometry and microhardness) NaF varnish increased hardness, but did not reduce roughness. TiF 4 varnish was not able to increase hardness and reduce roughness. Vieira et al. [8] 2007 in vitro 11 subjects for each agent containing 4 enamel blocks of 3 rd molars fluoride varnish Sprite soft drink (ph = 2.81) (profilometry ) Fluoride varnish was effective in reducing erosive wear. 58 Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64

Table 3 continued. Author Year Study Sample Fluoride Agent Erosive Agent Study Analysis Results Magalhães et al. [6] (profilometry ) Wiegang et al. [30] 2008 in vitro n = 12 for (bovine 2008 in vitro n = 6 for each group (bovine NaF varnish (2.26%F), NaF/CaF 2 varnish (5.63 % F ), 4% TiF4 varnish (2.45%F), and 4%TiF 4 solution (2.45 % F) with concentrations of 4% TiF 4, 10% TiF 4, 4%ZrF 4, 10% ZrF 4, 4% or 10% HfF 4 Sprite soft drink (ph = 2.6) (ph = 2) quantification (colorimetry ) TiF 4 varnish showed the best result by reducing after erosion. The erosion was reduced by prior application of ZrF 4 and HfF 4 but with lowest results for TiF 4. Ganss et al. [18] 2008 in vitro n = 20 for group (3 rd SnCl 2 (815 ppm Sn), NaF (250 ppm F), SnF 2 (250 F and 809 ppm ppm Sn), AmF (250 ppm F) and AmF/SnF 2 (250 ppm F and 390 ppm Sn) citric (ph = 2.3) (SEM and microradiography) The was substantially inhibited by AmF/SnF 2 and SnF 2. Treatments with containing Sn were more effective Hove et al. [19] 2008 in situ 7 subjects for each agent containing 8 blocks of human molar enamel TiF 4, SnF 2 and NaF (0.01M) Depth and surface roughness (white light interferometry ) TiF 4 and SnF 2 and reduced depth by 100% and 91%, respectively. NaF did not show protective effect. Magalhães et al. [31] 2009 in situ/ex vivo 10 subjects for each group with 4 enamel blocks (permanent molar incisor and deciduous) TiF 4 solution Cola soft drink (ph = 2.6) The application of 4% TiF 4 solution increased the permanent enamel hardness after continuous erosion, but deciduous enamel was not affected. Murakami et al. [10] 2009 in vitro n = 30 for (3 rd molars and deciduou ) gel (1.23% F) and NaF varnish (2.26% F) Cola soft drink (ph = 2.3) Fluoride varnish and gel were able to inhibit the, especially in permanent teeth. Schlueter et al. [22] 2009 in vitro n = 30 for (3 rd with different concentrations of Sn and F- (1000 and 1500 mg / L F) citric (ph = 2.3) The higher concentrations were effective in reducing mineral loss. The efficiency increased proportionally to the concentrations of these compounds. Wiegand et al. [28] 2009 in vitro n = 12 for (bovine AmF (0.5 and 1% F) NaF (0.5 and 1% F ) and SnF 2 (0.5 and 1% F) (ph 2.6) SnF 2 and AmF at the same concentrations were more effective in preventing mineral loss than NaF. Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64 59

Table 3 continued. Author Year Study Sample Fluoride Agent Erosive Agent Study Analysis Results Venasakulch ai et al. [23] 0-450 ppm fluoride solution citric (ph = 2.3) 2010 in vitro n = 6 for each group (bovine The was inversely proportional to the fluoride concentration. Yu et al. [9] 2010 in vitro n = 20 for TiF 4, NaF, AmF, ZnF 2 or SnF fluoride citric (ph = 2.6) (profilometry and SEM ) The lower ph of presented lower. High TiF 4, AmF and SnF 2 concentrations were effective in inhibiting erosion. Hove et al. [20] 2011 in vitro n = 5 for each group TiF 4 :0.5 M F and ph 1.2; 0.05 M F and ph 2.1, 0.5 M F ph 2.1 and, 0.05 M F ph 1.2 (white light interferometry ) The reduction of TiF 4 concentration and the increasing of ph decrease the protective effect. Vieira et al. [25] 2011 in vitro n = 6 for each group (bovine TiF 4 at concentrations of 0.1, 0.5, 0.75 and 1 % applied to single and multiple sessions Sprite soft drink The concentration of 0.5% showed the lowest mineral loss and 1% the highest concentration. Multiple applications of 0.5% solution significantly reduced mineral loss. Faller et al. [26] 2011 in vitro n = 10 for Toothpaste with SnF 2, NaF and SMFP and phosphoric Depth of mineral loss The dentifrice with SnF 2 showed lower compared to dentifrice with NaF and SMFP. TiF 4: titanium tetrafluoride; NaF: sodium fluoride; AmF: amine fluoride; ZnF 2 : zinc fluoride, SnF : stannous fluoride, ZrF 4: zirconium tetrafluoride; HfF 4: hafnium tetrafluoride; KNO 3: potassium nitrate; CPP: casein phosphopeptides; ppm F: parts per million of fluoride; SEM: scanning electron microscopy; SMFP: sodium monofluorophosphate. Furthermore, review studies evaluating the effect of these agents in the prevention of dental erosion are scarce, but this type of study has relevance to guide professionals who deal with patients at risk for the development of dental erosion on the possibilities and effectiveness of products for preventing dental erosion. Most studies showed that fluorinated agents and those were effective in preventing the development of dental erosion and evaluated mainly the of the dental tissue (Tables 3 and 4). Importantly, these studies were conducted in vitro, and there is difficulty in extrapolating results to the clinical practice. Furthermore, the types of erosive agent, protocols used for erosion development and methods to evaluate, roughness and surface analysis varied among studies, highlighting the need for standardization of erosion development in in vitro studies and protocols for the application of products. Currently, the use of fluorides related to dental caries is recommended after risk assessment and caries activity, with indication of topical fluoride application for the remineralization of white spot lesions. The process of dental caries development is different from erosion; however, fluoride agents used in the prevention of dental caries are also indicated for the prevention of erosive lesions, especially gels and varnishes with high fluoride concentration. Unfortunately, the use and application of fluoride agents in preventing erosion is still controversial because the positive results regarding the use of fluorides in dental erosion in in vitro and in situ studies do not demonstrate the multiple attacks that occur daily on the tooth surface or show the effect of saliva on the process. The studies reviewed found that fluoride can be beneficial for enamel remineralization in the 60 Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64

erosion process, but there is still need for studies evaluating the effect of topical fluoride application on the prevention of enamel demineralization as a result of dental erosion. The scarcity of randomized and controlled trials related to this issue leads to the lack of clinical protocols for the treatment and prevention of dental erosion with fluoride agents, as for dental caries, which is vital for clinicians to perform an appropriate preventive treatment to their patients. Table 4. Studies on CPP-- containing agents in the prevention and control of dental enamel erosion in the period from 2003 to 2012. Author Year Study Sample Fluoride Agent Erosive Agent Study Analysis Results Ramalingan et al. [39] enamel surface by SEM 2005 in vitro n = 5 for (3 rd with concentrations of 0.063%, 0.09%, 0.125% and 0.25% Powerade sports drink (ph=2.7) The degree of effectiveness was directly proportional to the CPP- concentration. Yamaguchi et al. [34] 2006 in vitro n = 6 for (bovine lactic (ph=4.75) enamel surface by ultrasound transmission speed CPP- at high concentrations increased enamel remineralization. Rees et al. [37] 2007 in vitro n = 10 for (3 rd proenamel or mousse 0.2% citric Products reduced. Proenamel showed the lowest mineral loss. Piekars et al. [38] 2008 in vitro n = 6 for (pre Mousse white wine (ph = 3.5) Depth of erosion by SEM The mousse reduced the erosion depth. Panich et al. [36] Poggio et al. [35] Ranjitkar et al. [11] 2009 in vitro n = 10 for 2009 in vitro n = 10 for 2009 in vitro n = 5 for (3 rd Mousse cola drink (ph = 2.7) cola drink (ph = 2.7) (ph = 1.2) enamel surface by AFM tooth wear CPP- increased the enamel hardness. CPP- protected enamel demineralization. Toothpaste with CPP- reduced enamel wear. Willershausen et al. [12] 2009 in vitro n = 5 for Apple juice (ph = 3.3) quantitative analysis of Ca and P by microanalysis electrosound Toothpaste with CPP- increased remineralization. Srinivasan et al. [13] 2010 in vitro n = 12 for (3 rd and + 900 ppm F cola drink SEM: scanning electron microscopy; SM: stereoscopic microscopy; AFM: Atomic Force Microscopy; Ca: calcium; P: Phosphorus. Both promoted surface remineralization, but the addition of 900 ppm showed better remineralization potential Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64 61

1. Fluoride agents The participation of fluoride is essential in preventing due to the formation of a fluoride reservoir on the tooth surface resulting from the deposition of CaF 2 globules [18]. This layer provides additional mineral to be dissolved during attack before underlying enamel being attacked, slowing down the demineralization process [18,19]. The formation of CaF 2 layer and the protective effect against dental erosion depend on ph, fluoride concentration and type of fluoride agent used. Six studies showed that the higher the fluoride agent concentration and the lower the product ph, the greater the effectiveness of the enamel erosion inhibition [9,20-24,26]. The deposition of CaF 2 globules is ph-dependent, since the reduction in the agent ph increases the fluoride concentration on the enamel surface, causing higher deposition of CaF 2 [9]. If fluoride agents contain metal ions (e.g. titanium and Sn), also in low ph, there will be an increased incorporation of these ions on the enamel surface [9]. Only one study demonstrated that the concentration of 0.5 % TiF 4 solution showed less mineral loss compared to 1% TiF 4 solution [25]. The high fluoride concentration is of utmost importance for the indication of in preventing dental erosion. According to the studies evaluated, dentifrices with higher fluoride concentration (450 ppm fluoride) were those with the greatest effectiveness in preventing after erosive challenge [21,26]. In addition, two studies showed that dentifrice with SnF 2 showed less compared to dentifrice with NaF [15,26]. The ability of residual fluoride from tooth brushing to have a preventive effect on future erosive challenge should also be evaluated. However, one study [26] investigated the residual effects of fluoride in saliva after the use of dentifrice containing NaF (1098 ppm F) and no protection against enamel erosion was observed. Thus, two studies [26,27] concluded that the benefit of fluoridated s against erosion is low and suggested that it seems satisfactory to indicate the use of s with high fluoride concentrations associated with other agents, also with high fluoride concentration to prevent dental erosion. Other fluoride agents include, gels and varnishes with fluorinated compounds that have been applied over the years in the prevention of dental caries such as NaF, AmF, SnF 2, SnCl 2 and TiF 4 [6,9,14,16,18,19,28,29]. All these studies reported little effect of the NaF compound in reducing surface roughness and after erosive challenge. Although NaF-based compounds are the most widespread, the ph of NaF is high and can influence the fluoride concentration on the enamel surface and the deposit of CaF 2 globules [9]. The use of SnF 2 increases the amount of Sn on the enamel surface, indicating a possible reaction between Sn and hydroxyapatite [18]. The protective effect of SnF 2 can be due to the formation of crystalline products, originated in specific conditions, such as Sn 2 OHPO 4, Sn 3 F 3 PO 4 and Ca(SnF 3 ) [18]. This is relevant because one study [18] demonstrated that salts containing Sn protect against erosion of the enamel surface because a stannous chloride solution (containing no fluoride) was evaluated and reduced by 65% the after erosive challenge. However, clinically, precipitation of phosphate containing fluoride and Sn can stain the demineralized enamel, being considered a disadvantage [18]. The AmF has low ph and forms larger CaF 2 globule precipitates, and it has already been demonstrated that the solubility of these globules decreases with the increase in size [9]. TiF4 has ic ph (about 1.2), inducing demineralization of the enamel surface and the formation of hydrofluoric (HF). This may increase the penetration depth of fluoride ions and promote the formation of CaF 2 [9]. Titanium ions play an important role, since they can replace Ca +2 ions of apatite and form a complex with oxygen from the phosphate group. This complex originates a stable glaze-type layer of titanium dioxide on the enamel surface [9,19,20]. The protective effect of TiF 4 is attributed to the formation of this titanium-rich layer, providing a mechanical barrier against the erosive attack for a certain period of time. Furthermore, it is suggested that the interaction of titanium with organic components of the surface leads to increased fluoride absorption [30]. Possibly, as a result of these factors, the selected studies showed greater protection to enamel erosion by agents containing TiF 4 [6,9,14,16,18,19,28-31]. However, one study highlighted that TiF 4 has not yet been introduced in the market due to the lack of toxicological studies with respect to this compound [20]. Fluoride may be effective in reducing, but as for s, the effectiveness increases proportionally with the increase of fluoride content [22,23]. Based on the results shown in Table 3, NaF solution showed no significant protection against enamel erosion [14,15], probably due to its high ph, as previously explained [9]. When compared to fluoride varnish and gel, the AmF solution also showed no protective effect on dental enamel [29], but was superior to NaF [9]. Thus, the showing the best results on reducing were those with TiF 4, SnF 2 and AmF [9,14,16,18,19,28,30] compounds. When compared to SnF 2, NaF, AmF and ZnF2, the TiF 4 solution showed better results [9,14,16,19]. However, more studies are needed to compare the effectiveness of different compounds and fluoride salts, since one cannot say which is the most effective. Gels are more used than, especially in children, because they flow less than and facilitate application. Acidulated fluoride gels showed greater effectiveness in protecting the enamel against erosion when with 1.23 % NaF [10] and also with AmF compound with 12.500 ppm F [32]. However, when compared to TiF 4 varnish, this presented better results [29]. Varnish has been considered one of the best vehicles to release therapeutic agents onto the tooth structure because it has the ability to adhere to the tooth surface due to the presence of a resin base, increasing 62 Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64

the contact time of the agent with the tooth structure [8]. A reservoir of calcium fluoride is formed due to the high fluoride concentration, allowing longer action of fluoride, besides acting as a mechanical barrier [8]. In all studies shown in Table 3, varnish containing NaF, the most widely used today, showed positive results regarding inhibition [6,10,33]. Controversial results were found for TiF 4 (2.45% F), which was effective in protecting against erosion in one study [6], and in another, it was not able to increase the enamel hardness and even to reduce surface roughness [33]. More studies should be conducted with this type of varnish so that conclusions are made regarding its effectiveness against enamel erosion. Experimental agents have been developed by researchers and tested for their effectiveness against erosion, since these compounds have already shown positive results against dental caries [30]. Hf and Zr tetrafluorides were added to and showed higher effectiveness than TiF 4 solution in relation to [30]. However, more studies are needed so that these products can be sold in the market. 2. CPP -containing agents In addition of fluoride, products based on casein, a milk derived protein, have been developed to prevent dental erosion [32]. Casein phosphopeptides (CPP) stabilize calcium and phosphate keeping them in the amorphous form, i.e., biologically active, known as (amorphous calcium phosphate). The CPP- combination is adsorbed on the tooth surface, increasing the level of calcium phosphate in the dental biofilm and releasing calcium and phosphate ions to the tooth when in an ic environment. This results in supersaturation of calcium and phosphate ions, which helps preventing demineralization and provides immediate remineralization of the enamel surface [34]. Casein can be adjusted to different ph levels. At ic ph, separates from CPP, increasing calcium and phosphate in the saliva; these ions are stabilized and spontaneous calcium phosphate precipitation does not occur, leaving ions free to remineralization [35]. CPP in combination with amorphous calcium phosphate (CPP-) is a product commercially available in the form of chewing gum, drinks, and mousse [36]. Based on the results shown in Table 4, CPP- obtained protective effect on tooth demineralization caused by erosion, regardless of the form of application, paste, cream or mousse [35]. CPP- promoted an increase of the surface hardness [36], reducing tooth wear [11,37] and erosion depth [38]. In addition, CPP- increased remineralization of the eroded enamel [12,34]. These results showed that CPP--containing products can be an alternative for preventing tooth enamel erosion. However, in one study [32], AmF gel was more effective in preventing than dentifrice and 250 ppm (Table 3). Moreover, association of CPP- with 900 ppm fluoride showed better remineralization potential compared to dentifrice containing only CPP- [13]. Modifications in drink formulations have been researched to make them less erosive due to the unlikelihood of individuals to stop drinking soft drinks, juices and sports drinks face the possibility of developing dental erosion. These modifications are made by adding ions already present or which can be incorporated into the product, making it less unsaturated in relation to the tooth tissue, thus being less erosive [39]. CPP- is one of these compounds that can be added to drinks. One study [38] demonstrated that when CPP- was added to sports drinks in concentrations of 0.063%, 0.09 %, 0.125 % and 0.25%, it reduced the erosive capacity of drinks, increasing their ph. The study also showed that the higher the CPP- concentration in the drink, the higher its effectiveness. 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Received: 27/05/2013 Approved: 19/11/2013 Correspondence: Profa. Fabíola Galbiatti de Carvalho Universidade Federal da Paraíba - Centro de Ciências da Saúde Departamento de Clínica e Odontologia Social Cidade Universitária - Campus I - João Pessoa - PB CEP: 58051-900 Phone: (83) 3216-7251 E-mail: fabigalbi@yahoo.com.br 64 Pesq Bras Odontoped Clin Integr. 2014; 14(1):55-64