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The Release of Ions from Metallic Orthodontic Appliances
The Release of Ions from Metallic Orthodontic Appliances Luciane Macedo de Menezes and Cátia Cardoso Abdo Quintão Several metallic alloys used in orthodontics have nickel and chromium as their components. These metal ions are known to be essential elements for human beings but are considered one of the most common causes of allergic contact dermatitis. The allergic reactions are caused by a direct relationship with the presence of this metal in the environment and may be caused by ingestion or direct contact with the skin and/or mucosa. The association of different metals in the oral environment may produce electrogalvanic currents and consequently, corrosion, with different levels of ions being released. The purpose of this article is to review the release of ions from metallic orthodontic appliances and its implications, as well as to provide suggestions for the management of this problem in the orthodontic office. (Semin Orthod 2010;16:282-292.) © 2010 Elsevier Inc. All rights reserved.
here is increasing concern about the biocompatibility of dental materials1 and, therefore, this topic has been widely investigated during recent years. The metals that are released from biomaterials in various sites of the human body have attracted the interest of many investigators because it is believed that the degradation products can elicit a foreign-body reaction or induce pathologic processes. Particularly in orthodontics, there is interest in investigating reactions secondary to the use of metals that are known allergens.1 Major emphasis has been placed on the levels of nickel and chromium in fluids, such as saliva,2-4 blood,5 or urine.1 However, studies on these issues have given rise to questions without answers, confirming the need to learn more about the biocompatibility of dental materials.2
T
Department of Orthodontics, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. Department of Orthodontics, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil. Address correspondence to Luciane Macedo de Menezes, DDS, MS, PhD, Assistant Professor, Department of Orthodontics, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681—Predio 6, Sala 209, Porto Alegre, Brazil. E-mail: [email protected] © 2010 Elsevier Inc. All rights reserved. 1073-8746/10/1604-0$30.00/0 doi:10.1053/j.sodo.2010.06.006
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Most orthodontic appliances are made from a stainless-steel alloy, containing approximately 6% to 12% nickel and 15% to 22% chromium,6 and, because they are continuously exposed to saliva, the metals must exhibit corrosion resistance.7 All metals and alloys are subject to corrosion. The alloy’s ability to be biocompatible appears to be related to its pattern and mode of corrosion. Corrosion is an electrochemical process that results in the loss of the essential metallic properties of a metal. Metal destruction by corrosion occurs either through loss of metal ions directly into solution or by progressive dissolution of a surface film, typically an oxide or sulfide, on the metal.7 The resulting products might trigger inflammatory responses of the soft tissues and cause irritation or dermatitis.8
The Relationship Between Corrosion and Biocompatibility The resistance to corrosion is a fundamental aspect of biocompatibility and may be affected by several factors, such as the manufacturing process, type of alloy, surface characteristics of the piece,6 environment in which the piece is inserted,9 and use of the alloy (aging).2 Corrosion releases metallic ions into solution, either directly or through dissolution or destruc-
Seminars in Orthodontics, Vol 16, No 4 (December), 2010: pp 282-292
Release of Ions from Metallic Orthodontic Appliances
tion of surface oxide or other films and, in the clinical setting, such metallic ion release may elicit adverse patient reactions, many of which have been reported in the literature.7 One of the most common reactions is the hypersensitivity to nickel, due to a direct relationship with the presence of this metal in the environment, and may be caused by ingestion or direct contact with the skin and/or mucosa. However, some questions remain to be answered. How much of the corrosion products are actually absorbed by the organism?5 Is the amount of metal released sufficient to sensitize a person or to maintain a reaction in a previously sensitized person?
The Role of Corrosion on the Release of Ions The microstructure of a metal is a basic parameter that affects both its mechanical properties and, in particular, its corrosion behavior. Variations in manufacturing technique and postmanufacturing finishing and polishing operations might affect the corrosion behavior of orthodontic appliances.7,10 Three principal methods are used to manufacture brackets, namely casting, machining or milling, and powder metallurgical (sintering) techniques. Cast and sintered brackets are manufactured in a near-finished condition, but with milled brackets, the slots and wings are machined into lengths of rolled strip that is then cut into individual brackets. With regard to wires, manufacturers are well aware of the susceptibility of orthodontic alloys to the various forms of corrosion and have taken some steps to combat this potentially destructive process: alloy substitution or addition (the addition of certain metals to an alloy can reduce its susceptibility to corrosion), coatings (orthodontic archwires and brackets can be coated with either titanium nitride or an epoxy resin) and modification of the production process. Mechanical or chemical disruption of the protective film, or exposure to a medium that dissolves the film and prevents its reformation, will result in corrosion. Corrosion involves two concomitant reactions, an oxidation reaction at the anode and a reduction reaction at the cathode. Commonly, the anodic reaction will continue until there is total consumption of the metal, unless the metal can form a protective
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surface film (a process known as passivation) or the cathodic reactant is consumed. An alternative and industrially important means of controlling or preventing corrosion is to add to the solution an inhibitor, a substance that reacts with the metal to form a protective film on its surface. Although adding a corrosion inhibitor to the oral environment is generally not possible, there are indications that certain naturally occurring proteins in saliva are corrosion inhibitors. Depending on the thermodynamics and kinetics of the overall reaction, corrosion may proceed slowly or rapidly and occur as a general or localized attack.7 Chromium ions provide an electrochemically formed passive film that offers protection against aggressive ions in the oral environment and prevents corrosion. This effect increases as the chromium content increases. As a result, stainless-steel and chromium-containing alloys do not corrode easily. The mechanism occurs by creating a thin oxide film, which delays corrosion. Integrity of chromium oxide on a metal surface is very important and chromium oxide must be maintained and kept stable throughout the entire material.11 However, when stainless steel is heat-treated or when bends or welds are made in wires, surface oxidation might occur, and an uneven oxide film may cause localized corrosion. Each heat treatment environment and cooling method can affect the thickness and form of the uneven oxide film on the wire surface, which can create various degrees of corrosion. The level of corrosion of any metal and the release of ions depends on the chemistry of the solvent in which it is immersed, the pH of the solution, and the length of immersion. To evaluate some of these parameters (pH value, length of immersion and type of archwire) on release of metal ions from orthodontic appliances, simulated fixed orthodontic appliances were immersed in artificial saliva of different pH values during a 28-day period. Three types of archwires were used: stainless steel, nickel-titanium (NiTi), and thermo NiTi. The quantity of metal ions was determined using a high-resolution mass spectrophotometer. The release of six different metal ions was observed: titanium, chromium, nickel, iron, copper, and zinc. Results showed that the appliances released measurable quantities of all ions examined; the
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change in pH had a very strong effect (up to 100-fold) on the release of ions; and the release of ions was dependent on wire composition, but, it was not proportional to the content of metal in the wire. The largest number of ions was released during the first week of appliance immersion. All three observed parameters (chemical composition of the archwire, pH value of the artificial saliva, and time of exposure to the solution) influenced ion release.12 The greatest release of ions occurred during the first 7 days with a gradual decline thereafter. This finding cannot be ascribed to saturation of the solution with metal ions because the solution was changed for every time period. This kinetics of ion release can be explained by an initial surge of ion release from the metal surface or by formation of a stable oxide layer that slows down further ion release.13 Decreasing the pH from 6.75 to 3.5 increased the release of ions on average 37-fold, with the largest increase for chromium (1:106) and the smallest for titanium (1:7). These results confirm the hypothesis that low pH values reduce the resistance of dental alloys to corrosion.12,14
Metals That Are Released from Orthodontic Appliances The major corrosion products are iron, chromium, and nickel for stainless steel and titanium and nickel for nickel–titanium alloys.11 The oral environment is considered hostile and potentially corrosive.10 Among stainless-steel and nickel– titanium corrosion products nickel and chromium have received the most attention because of their reported adverse effects.11 Nickel is the most common cause of contact allergy15 and is known to trigger more allergic reactions than all other metals combined. In addition to the allergic issue, carcinogenic, mutagenic, and cytotoxic effects have been assigned to nickel and, to a lesser extent, chromium.2 Nickel is not a cumulative toxin; it is absorbed in the gastrointestinal tract and eliminated by its metabolic route.16 The main route for elimination of nickel is through the kidneys; nearly 90% is quickly excreted in urine.17 For patients with no occupational exposure to nickel, the mean urinary nickel level is about 4.5 g/L (range, 1.9-9.6 g/L) or, according to other authors, up to 50 g/L. Nickel can also be eliminated in
saliva and sweat; this might contribute to increased excretion in high-temperature areas.1 Studies have demonstrated that other ions present in the silver solder, such as cadmium, copper, silver, and zinc, may be released in the oral cavity, whose exposure may determine several adverse effects with direct toxic alterations in an acute or chronic manner.18 Such metallic ions are potentially dangerous chemicals, being included in the list of substances and processes that pose high risk to human life because of their carcinogenic potential to the lung, prostate, and kidneys, in addition to alterations in the hematopoietic, urinary, and digestive systems.
Signs of Corrosion of the Orthodontic Appliances The corrosion processes of the orthodontic appliances, when severe, may be observed by the naked eye as a discoloration (change of enamel color around the brackets),19 as the result of the deposition of corrosion products. Furthermore, corrosion is a continuous process, and its effects are cumulative so that in the bracket slot, there may be a progressive increase in surface rugosity or a corrosion product buildup over time. This may cause increased frictional resistance to orthodontic sliding mechanics and adversely affect the progress of treatment.7 Often, the corrosion process may be invisible and quantified only by the concentration of the ions released.
Evaluation of the Ions Released from Orthodontic Appliances There are three ways of investigating metal ion release: in vitro, retrieval (ex vivo investigation of in vivo aged samples), and in vivo.19 Comparisons with in vitro studies are necessary, yet limited, because of variations in methodology, such as the immersion solution. The most frequent solutions used are saline solutions (0.05% or 0.9%) or artificial saliva with different compositions. The storage method may also vary between static and dynamic media according to changes of solution to avoid saturation.2
Release of Ions from Metallic Orthodontic Appliances
In Vitro Study Evaluations and Their Usefulness Several questions are evaluated or answered based on in vitro studies. What are the ions released from orthodontic appliances and amount released? Can the type of alloy used in the fabrication of the brackets have an influence on the quantity of ions released? Is the release pattern of new and recycled brackets the same? Do titanium brackets, one of the alternatives to stainless steel, corrode? Do these brackets release ions? Studies that address some of these issues are listed in Table 1. The quantities of released metal ions measured in some in vitro studies are useful for relative comparisons and for determination of the effect of each individual variable on ions released without the influence of external factors.12 One of the first studies to research this topic was conducted by Park and Shearer in 1983. They verified that the amount of nickel released in vitro by a simulated orthodontic appliance was about 40 g per day.20 Because human dietary intake of nickel is reported to be 300 to 500 g per day,21 the release of 40 g of nickel per day is well below the normal daily intake and may not be of clinical significance.20 To assess whether the type of alloy used in the fabrication of the brackets can have any influence on the quantity of ions released, 2 groups of stainless steel brackets were formed: group A (American Iron and Steel Institute [AISI] 303) and group B (AISI 316 L). The specimens (simulated orthodontic appliances) were put in saline solution (0.05%), in a precision shaking Dubnoff incubator (Precision Scientific Co., Chicago, IL), at 36°C, for 60 days. The ion release was detected by atomic absorption spectrophotometer. The weight of the brackets was also measured before and after the test. The results indicated that group A released more nickel and chromium ions than group B. Moreover, the brackets in group A also presented weight loss, which is considered an indicator of corrosion. It was concluded that, under the study conditions, the brackets from group A presented higher biodegradation than group B brackets, which could be associated with the composition and manufacturing process of these brackets.22 Another issue investigated was the ion release pattern of new and recycled stainless steel brackets. To evaluate it, new and recycled brackets
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were immersed in buffers of different pH values over a 48-week period. The release of nickel, chromium, iron, copper, cobalt, and manganese ions was analyzed by atomic absorption spectophotometry. The results showed that recycled brackets released more ions than new brackets. Brackets immersed in solutions of pH 4 released more ions than those immersed in solutions of pH 7, and the total amount of ions released increased with time over the 48-week period. This study demonstrates that both new and recycled brackets will corrode in the oral environment. It has been suggested that the microstructural changes after recycling, because of the cleaning and sterilization procedures involved, result in an increase in corrosion7 that contraindicates the use of recycling. To avoid clinical side-effects, metal brackets more resistant to corrosion should be made, and recycled brackets should not be used.4 These results were later corroborated and, in some countries, such as the United Kingdom, the practice of recycling is no longer recommended.10 Titanium brackets are of interest because their use is advantageous in the orthodontic treatment of patients with an allergy to nickel and other specific substances. However, in an in vivo investigation, performed by Harzer et al,23 that tested how the surfaces of titanium brackets react to the corrosive influence of acidic fluoride-containing toothpaste during orthodontic treatment, the authors observed that significantly more plaque accumulated, and a more marked change of color occurred on the surface of titanium brackets than on stainless-steel brackets. The surface of the rolled wings of titanium brackets was very rough, and the biocompatibility of titanium supports plaque adherence, serving as a depot for bacteria and electrolytic medium for different ions. The slots of titanium brackets are not as rough as the wings because the slots are milled and not rolled. The manufacturer should modify the production process and mill the entire bracket. Despite this, the researchers comment that titanium brackets can safely be used.23
Important Aspects of In Vivo Studies The administration and elimination routes are important aspects for understanding the reactions to metals.1 Blood, urine, and hair are the most accessible tissues for measurement of ex-
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Table 1. Some Research Regarding the In Vitro Release of Ions From Orthodontic Appliances Author/Year
Study Purpose
Barret, Bishara and Quinn (1993)43
To compare in vitro the corrosion rate of a standard orthodontic appliance
Park and Shearer (1993)20
To evaluate the amount of nickel and chromium released from a simulated appliance To evaluate the release of nickel and chromium from five samples consisting of braces, extraoral and quad-helix
Kerusuo et al (1997)24
Solution/Evaluation Time
Brackets Bands and brackets (AISI 305 and 316) bondable brackets (AISI 303 and 304)
Artificial saliva medium at 37°C days 1, 7, 14, 21, 28
Sodium chloride 0.05% solution
Sodium chloride 0.9% for 2 h, 24 h, and 7 d
Huang et al (2004)4
Compare the release of metal ions from new and recycled brackets
Tomy, Ormco, Dentaurum, 3M Unitek
Artificial saliva (with different pH values over a 48-week period)
Dolci et al (2008)22
To evaluate, in vitro, the biodegradation of simulated orthodontic appliances consisting of stainless steel brackets and wires
Group A (AISI 303); and group B (AISI 316 L).
Saline solution (0.05%), in shake, at 36°C days 7, 14, 28, and 60
Sfondrini et al (2009)44
To test the hypothesis that there is no difference in the amounts of chromium released from new or recycled stainless steel brackets, and nickelfree brackets.
Stainless-steel brackets, stainless-steel recycled brackets and Ni-free brackets
Artificial saliva at various acidities (pH 4.2, 6.5, and 7.6) 15 min, 1 h, 24 h, 48 h, 120 h
posure or dose to a product or substance, and are sometimes mentioned as indicator tissues. Despite this, the most significant method for measurement of nickel release before and after onset of orthodontic treatment is salivary analysis because it is the first diluents of the human
Conclusion Orthodontic appliances release measurable amounts of nickel and chromium when placed in an artificial saliva medium. For both arch wire types, the release for nickel averaged 37 times greater than that for chromium. Release of 40 g of nickel and 36 g of chromium per day.
Detectable release of nickel and chromium from orthodontic appliances seems to occur, and the amount of nickel released increases in dynamic conditions. The authors commented that the amount released may be considered negligible under a toxicologic point of view, but can be of considerable importance for individuals with a high degree of sensitivity to níckel. Recycled brackets released more ions than new brackets. Brackets immersed in solutions of pH 4 released more ions than those immersed in solutions of pH 7, and the total amount of ions released increased with time over the 48-week period. Brackets from group A presented a higher biodegradation than group B brackets, that could be associated to composition and manufacturing process of these brackets. The greatest amount of chromium was released from new stainless-steel brackets. The smallest release was measured with Ni-free brackets. The difference between recycled brackets and Ni-free brackets was not statistically significant. For all brackets, the greatest release was measured at pH 4.2.
body and allows long periods of analyses.19 The warm and moist condition in the mouth offers an ideal environment for the biodegradation of metals, consequently facilitating the release of metals ions that can cause adverse effects. However, there is little qualitative or quantitative
Release of Ions from Metallic Orthodontic Appliances
data available on the release of metals or metallic salts within the oral cavity.11
The Relationship Between Blood, Urine, and Ions Release An important question is whether orthodontic patients accumulate measurable concentrations of nickel in their blood during the initial course of orthodontic therapy. To address this question blood samples were collected at three different times: before the placement of orthodontic appliances, 2 months after their placement, and 4 to 5 months after their placement. The study involved 31 subjects; 18 female and 13 male, between 12 and 38 years of age—all had malocclusions that required the use of a fully banded and bonded edgewise appliance. A total of 93 blood samples (3 from each patient) were analyzed by atomic absorption spectrophotometry. The results obtained from this investigation indicate that orthodontic appliances used, in their “as-received” condition, corrode in the oral environment releasing both nickel and chromium, in amounts significantly below the average dietary intake. Furthermore, the biodegradation of orthodontic appliances during the initial 5 months of treatment did not result in significant or consistent increase in the blood level of nickel.5 The pretreatment and treatment levels of nickel in the urine of 21 orthodontic patients (12 female, 9 male patients) wearing fixed appliances were evaluated. This was done before placement of orthodontic appliances and 2 months after placement. Nickel ion analysis was carried out by the use of atomic absorption spectrophotometry. Urinary nickel levels increased significantly after the placement of orthodontic appliances, for both sexes. The biological effect of a systemic increase in urinary nickel is unknown. Long-term follow-up and larger samples of patients are needed to validate the results and to determinate the implications of these findings.1
Concentrations of Metal Ions Released in Saliva The large variability in ion concentration among subjects is a common finding when the release of metal ions in saliva is examined.24-27 This variation may be related to several factors be-
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cause saliva does not present a constant composition and may be different among individuals or even among periods for the same individual. The physical properties, amount, and composition of saliva are influenced by factors, such as diet, period of the day, and psychic conditions.26 The actual amounts of nickel and chromium released from fixed appliances have been distinct but low, and well below the normal daily intake of nickel in diet. The literature includes some in vivo studies evaluating the ion release in saliva (Table 2). In an effort to understand the issues on ion release and its biological effects, in vivo research was conducted. Saliva from 31 subjects, before the placement of brackets and 3 weeks after placement, was collected. The nickel and iron were quantified by atomic absorption spectroscopy. The only difference observed for the concentration and volume of nickel and iron, was immediately after placement of the appliance, when there was a significant increase. So it seems that there is a high initial release of metals, but this effect decreases with time.26 In 1997, the salivary concentrations of nickel and chromium in patients wearing different types of appliances were evaluated, by Kerosuo et al.24 The study sample was composed of 47 patients, and 4 saliva samples were collected: before placement of the appliance, after 2 days, after 1 week, and after 1 month. The mean salivary concentration was 55 ng/mL for nickel and 61 ng/mL for chromium, similar to the values observed before placement of the appliance.24 The concentration of nickel in the saliva and dental biofilm in young patients, who wore and did not wear fixed orthodontic appliances, was compared. When the saliva samples were taken, the appliances had been in place an average of 16 months in the group who wore the appliances. A significantly greater content of nickel was found in the plaque and saliva of patients with orthodontic appliances (median values for nickel in the saliva were of 25.3 and 14.9 g/g, for patients with and without orthodontic appliances, respectively).28 In another study, the alterations in the chromium and nickel concentrations in the saliva of orthodontic patients treated with fixed orthodontic appliances were evaluated. Forty-five orthodontic patients were included in this study. The first group consisted of 15 patients (7 fe-
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Table 2. Some Research Regarding the In Vivo Release of Ions from Orthodontic Appliances (Saliva) Author/Year
Ions
Sample
Characteristics
Duration
Results
Before insertion of the appliance, 2 d 1 wk and 1 mo Before insertion of the appliance, 1 wk, 1 and 2 mo
No differences before and after appliance. No differences between groups.
Before insertion of the appliance, 1 wk, 1 mo, 1 year, and 2 years
Reached their highest levels in the first mo and decreased to their initial level in the rest of the groups. No differences between groups. Metal levels did not exceed those of daily intake. Increase of ions during treatment.
Kerosuo et al 199724
Chromium, nickel
47 patients
Different types of appliances
Kocaderelli et al, 200025
Chromium, nickel
30 patients (15 control)
Agaoglu et al, 200129
Chromium, nickel
100 patients
Fixed appliance15; fixed appliance in maxillary arch15 Fixed appliance
Eliades et al, 200345
Chromium, nickel, ferrous
17 patients (7 control)
Fixed appliance
Salivary sample obtained at least 15 mo after appliance
Ramadan 200427
Chromium, nickel
20 patients
Fixed appliance in maxillary arch
Fors and Person, 200628 Souza and Menezes, 20082
Nickel
17 patients (24 control) 30 volunteers
Fixed appliance
Initial, 3 and 12 mo and 1 mo after debonding 48 h
Freitas, 200818
Cadmium, copper, zinc, silver
30 patients (30 control)
Petoumenou et al, 20093
Nickel
17 patients
Chromium, nickel, iron
Removable appliance with bonded brackets (AISI 303 and 316 L) Hyrax appliance
Fixed appliance and Ni–Ti archwires
male, 8 male) with fixed appliances placed in their upper and lower arches. The second group consisted of 15 patients (8 female, 7 male) with a fixed appliance placed only in the upper arch. The control group consisted of 15 patients (7 female, 8 male) who were not undergoing orthodontic treatment. Four samples of stimulated saliva were collected from each patient before insertion of the fixed appliance, 1 week after insertion of the appliance, 1 month after insertion of the appliance, and 2 months after insertion of the appliance. The same four samples of saliva were collected from each control patient at the same time intervals as for the fixed-appliance groups. It was observed that there was a large variation in the concentrations of both nickel and chromium in saliva. No significant
Initial, 10 min 24 h, 7, 30 and 60 d after placement of the appliance Initial, 10 min 24 h, 7, 30 and 60 d after placement of the appliance
2-8 wks after placing the wires
Increase of ions in patients with appliance. Increase of chromium and nickel ions. Increase of ions, with high concentrations immediately after placement of the appliance and tendency of regression within the study period. Increase of ions after placement of band and archwire.
differences were found between the nonappliance group and the samples obtained after insertion of the appliances. The results of the study suggest that fixed orthodontic appliances do not significantly affect nickel and chromium concentrations of saliva during the first 2 months of treatment.25 To test the hypothesis that toxic metallic ions present in silver solder used in orthodontics are released in human saliva, 60 subjects were divided into 2 groups (n ⫽ 30, each): control and study (in need of maxillary expansion with the Hyrax appliance). For analysis of the release of metallic ions, saliva samples were collected from each patient at 6 periods. For both groups it consisted of initial, 10 minutes, 24 hours, and 7, 30, and 60 days after placement of the Hyrax
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appliance. The analysis of saliva was performed by atomic absorption spectophotometry in a graphite oven, determining the concentration of cadmium, copper, zinc, and silver ions. The ion concentrations in the control group exhibited low values for cadmium, copper, and zinc, whereas for the silver ion the values did not reach the detection limit. In the study group, all ions presented expressive concentrations at 10 minutes after placement of the appliance, with higher means for copper, with a tendency for reduction after 24 hours. Comparison between groups revealed significant differences for copper (all periods), zinc (10 minutes, 24 hours, and 7 and 30 days), and for cadmium only at 10 minutes. There was a great release of the ions analyzed in the study, with high concentrations measured immediately after placement of the appliance, but with a tendency to regress within the study period.18
appliances were higher in orthodontic patients than in controls and that nickel released from fixed orthodontic appliances could induce DNA damage in oral mucosa cells.30 The differences between the studies of Faccioni et al30 and Westphalen et al,31 regarding the genetic damage, may be explained by the fact that the study conducted by Faccioni et al30 was a cross-sectional study associated with a larger number of patients analyzed using the appliances for a much longer period (2-3 years). The paucity of research in this field and the importance of the issue in health of the orthodontic patients justify further studies with larger samples and long-term follow-up analysis. These strategies will yield valuable data to better understand the genotoxic potential of metals from orthodontic devices, as well as to assess the biological risk to which orthodontic patients may be submitted.31
Genotoxic Effects from the Ions Released in Oral Cavity
Possible Local or Systemic Effects From Ions Release
Although the amount of metals released from orthodontic appliances is significantly below the average dietary intake and does not reach toxic concentrations,25,29 it cannot be excluded that it can be sufficient to induce biological effects in cells from the oral mucosa.30 Westphalen et al31 assessed the genotoxicity effects from orthodontic appliances by carrying out both micronucleus (MN) and comet (CA) assays in a group of 20 healthy patients undergoing orthodontic treatment. The combination of MN and CA assay is recommended because the CA can be used to detect primary DNA damage (reparable) in a short period, whereas the MN assay detects chromosomal damage in a further stage. In the study conducted by Westphalen et al, the time of sampling was 10 days after the placement of the orthodontic appliance for the CA and 20 days later (30 days after appliance placement) for MN assay. The CA results revealed that orthodontic appliances did not induce any genetic damage. The MN assay showed an increase in MN cells 30 days after the placement of the orthodontic appliances.31 By contrast, when the CA was applied in an in vivo study, conducted by Faccioni et al,30 with 55 orthodontic patients and 30 control subjects, it was demonstrated that metallic ions (nickel) released from orthodontic
The introduction of metal ions into the human body is an additional risk to health which may lead to systemic and local effects.5 Hypersensitivity occurs when an adverse reaction follows contact with subtoxic doses of foreign substances. Three mechanisms comprise hypersensitivity reactions: allergy, intolerance, and hyperreactivity.21 Epidemiologic data demonstrate that the number of people with sensitivity to nickel has increased to approximately 20%.15,32 Contact with nickel by susceptible subjects can yield a wide range of hypersensitivity reactions.33 Nickel allergies may comprise extraoral and intraoral reactions though extraoral allergic reactions are more frequent than intraoral reactions. Nickel allergies may comprise intraoral red zones, blisters, and ulcerations, extending to the perioral area, and are referred to as allergic contact mucositis or dermatitis. Intraoral allergic reactions include redness, edema, itching and dryness of the lips and oral mucosa, burning sensations, as well as gingival inflammation. All these reactions are not necessarily limited to the exposure site. Eczematic and urticarial reactions of the face or more distant skin areas can occur with redness, irritation, itching, eczema, soreness, fissuring, and desquamation.21 Occasionally, fever has been reported as a systemic reac-
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tion.34,35 However, much remains to be understood and studied in terms of nickel, such as its release, absorption and reactions.
Evaluation of a Patient for Sensitivity to the Metal Ions Released When there is suspicion of an allergic reaction, the allergen must be determined. Hypersensitivity is usually diagnosed through patient history, clinical findings, and biocompatibility testing (patch tests).36,37 The literature includes some studies in which patch tests were used to evaluate the hypersensitivity reactions to nickel. Prystowsky et al33 evaluated a sample of 1158 adult volunteers and found that 5.8% had a positive reaction to 2.5% nickel sulfate (9% in women and 0.9% in men). There was a strong correlation between pierced ears, ear lesions, and areas of contact with jewelry. Among patients referred for clinical evaluation of contact dermatitis, 11% had a positive reaction to nickel. Blanco-Dalmau et al36 conducted a patch test to 5% nickel sulfate in 403 subjects (121 male, 282 female). The incidence of positive reaction in the study sample was 28.5%, with a remarkable difference between the sexes (31.9% of female subjects, compared with 20.7% of male subjects). Stenman and Bergman38 performed patch tests in 151 patients (119 female, 32 male) with reported hypersensitivity to the components of dental materials or trinkets. Positive response to metals was observed in 42 patients (28% of the sample), whereas reaction to organic components was observed in 7 patients (4.6%). A positive reaction to nickel was found in 21 patients (14%), including 20 women and 1 man. Jones et al17 attempted to determine the incidence of nickel hypersensitivity with patch tests in 100 patients (50 men, 50 women). The authors investigated the relationship between sex, age, and previous report of allergy to jewelry with hypersensitivity to this metal and found alterations in blood pressure, pulse, or temperature among patients with nickel hypersensitivity. Furthermore, by placing a removable appliance, the authors observed that nickel-hypersensitive patients were prone to demonstrate signs of hypersensitivity, at both the area of contact and distant areas. The authors found an incidence of hyper-
sensitivity to nickel with the patch test of 20% for women and 2% for men. Menezes et al39 evaluated hypersensitivity to eight antigens, some of them components of bands and brackets used in orthodontic practice. The tested substances were cobalt chloride, copper sulfate, potassium dichromate, iron sulfate, manganese chloride, molybdenum salt, nickel sulfate, and titanium oxide. They were removed after 48 hours and assessed by a dermatologist at 48 and 72 hours after antigen application. The patch tests were carried out before and 2 months after the placement of fixed orthodontic appliances. Statistically significant positive reactions were observed for nickel sulfate (21.1%), potassium dichromate (21.1%), and manganese chloride, 7.9%; reactions to nickel sulfate had the greatest intensity. No differences were observed between the reactions before and after placement of the orthodontic appliances; this indicates that they did not sensitize the patients or affect their tolerance to these metals during the study period. No statistical difference was observed regarding sex for any evaluated substance, although a greater tendency to positivity to nickel sulfate was observed among female patients and to potassium dichromate in male patients.
Procedures Recommended in Cases of Allergy to Nickel Firstly, good-quality materials should be used so that the effects of corrosion are minimized. The use of recycled brackets should be avoided and the use of alternative products, such as nickelfree, ceramic, polycarbonate, titanium, or goldplated brackets should be considered. When the allergic reactions do appear shortly after the placement of fixed orthodontic appliances, treatment must be discontinued and any appliances containing nickel removed.19,40,41 After healing, treatment should resume using alternative alloys.42
Conclusions Several questions remain unanswered concerning the biological effect of a systemic increase in nickel levels. In addition, there is a lack of information on abnormal accumulation of nickel in specific tissues of the body. The increase of
Release of Ions from Metallic Orthodontic Appliances
nickel in the patients, despite the low amounts in the composition of orthodontic appliances, is not easily explained. The differences in the changes of excretion of these metal ions might be due to differences in corrosion processes, solubility coefficients, or excretion mechanisms. Although increases in metal ion levels have been detected in some studies after placement of orthodontic appliances, the levels are not sufficient to cause alarm; however, additional in vitro and in vivo studies should be performed to clarify these questions and determine safe levels of metallic ions.
References 1. Menezes LM, Quintao CA, Bolognese AM: Urinary excretion levels of nickel in orthodontic patients. Am J Orthod Dentofac Orthop 131:635-638, 2007 2. Matos de Souza R, Macedo de Menezes L: Nickel, chromium and iron levels in the saliva of patients with simulated fixed orthodontic appliances. Angle Orthod 78: 345-350, 2008 3. Petoumenou E, Arndt M, Keilig L, et al: Nickel concentration in the saliva of patients with nickel-titanium orthodontic appliances. Am J Orthod Dentofac Orthop 135: 59-65, 2009 4. Huang TH, Ding SJ, Min Y, et al: Metal ion release from new and recycled stainless steel brackets. Eur J Orthod 26:171-177, 2004 5. Bishara SE, Barrett RD, Selim MI: Biodegradation of orthodontic appliances. part II. Changes in the blood level of nickel. Am J Orthod Dentofac Orthop 103:115119, 1993 6. Matasa CG: Attachment corrosion and its testing. J Clin Orthod 29:16-23, 1995 7. von Fraunhofer JA: Corrosion of orthodontic devices. Semin Orthod 3:198-205, 1997 8. Barceloux DG: Nickel. J Toxicol Clin Toxicol 37:239258, 1999 9. Staffolani N, Damiani F, Lilli C, et al: Ion release from orthodontic appliances. J Dent 27:449-454, 1999 10. House K, Sernetz F, Dymock D, et al: Corrosion of orthodontic appliances—should we care? Am J Orthod Dentofac Orthop 133:584-592, 2008 11. Amini F, Borzabadi Farahani A, Jafari A, et al: In vivo study of metal content of oral mucosa cells in patients with and without fixed orthodontic appliances. Orthod Craniofac Res 11:51-56, 2008 12. Kuhta M, Pavlin D, Slaj M, et al: Type of archwire and level of acidity: effects on the release of metal ions from orthodontic appliances. Angle Orthod 79:102-110, 2009 13. Eliades T, Zinelis S, Papadopoulos MA, et al: Nickel content of as-received and retrieved NiTi and stainless steel archwires: assessing the nickel release hypothesis. Angle Orthod 74:151-154, 2004 14. Huang TH, Yen CC, Kao CT: Comparison of ion release from new and recycled orthodontic brackets. Am J Orthod Dentofac Orthop 120:68-75, 2001
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15. Kerosuo H, Kullaa A, Kerosuo E, et al: Nickel allergy in adolescents in relation to orthodontic treatment and piercing of ears. Am J Orthod Dentofac Orthop 109:148154, 1996 16. Magnusson B, Bergman M, Bergman B, et al: Nickel allergy and nickel-containing dental alloys. Scand J Dent Res 90:163-167, 1982 17. Jones TK, Hansen CA, Singer MT, et al: Dental implications of nickel hypersensitivity. J Prosthet Dent 56:507509, 1986 18. Freitas MPM: Toxicity of Silver Solder Used in Orthodontics: “In Vitro” and “In Situ” Study. Porto Alegre, Pontifical Catholic University of Rio Grande do Sul, 2008 19. Eliades T, Athanasiou AE: In vivo aging of orthodontic alloys: implications for corrosion potential, nickel release, and biocompatibility. Angle Orthod 72:222-237, 2002 20. Park HY, Shearer TR: In vitro release of nickel and chromium from simulated orthodontic appliances. Am J Orthod 84:156-159, 1983 21. Kolokitha OE, Chatzistavrou E: Allergic reactions to nickel-containing orthodontic appliances: clinical signs and treatment alternatives. World J Orthod 9:399-406, 2008 22. Dolci GS, Menezes LMd, Souza RMd, et al: Biodegradation of orthodontic brackets: in vitro ion release. Revista Dental Press de Ortodontia e Ortopedia Facial 13:77-84, 2008 23. Harzer W, Schroter A, Gedrange T, et al: Sensitivity of titanium brackets to the corrosive influence of fluoridecontaining toothpaste and tea. Angle Orthod 71:318323, 2001 24. Kerosuo H, Moe G, Hensten-Pettersen A: Salivary nickel and chromium in subjects with different types of fixed orthodontic appliances. Am J Orthod Dentofac Orthop 111:595-598, 1997 25. Kocadereli L, Atac PA, Kale PS, et al: Salivary nickel and chromium in patients with fixed orthodontic appliances. Angle Orthod 70:431-434, 2000 26. Gjerdet NR, Erichsen ES, Remlo HE, et al: Nickel and iron in saliva of patients with fixed orthodontic appliances. Acta Odontol Scand 49:73-78, 1991 27. Ramadan AA: Effect of nickel and chromium on gingival tissues during orthodontic treatment: a longitudinal study. World J Orthod 5:230-234, 2004 28. Fors R, Persson M: Nickel in dental plaque and saliva in patients with and without orthodontic appliances. Eur J Orthod 28:292-297, 2006 29. Agaoglu G, Arun T, Izgi B, et al: Nickel and chromium levels in the saliva and serum of patients with fixed orthodontic appliances. Angle Orthod 71:375-379, 2001 30. Faccioni F, Franceschetti P, Cerpelloni M, et al: In vivo study on metal release from fixed orthodontic appliances and DNA damage in oral mucosa cells. Am J Orthod Dentofac Orthop 124:687-693, 2003; discussion: 693-684 31. Westphalen GH, Menezes LM, Pra D, et al: In vivo determination of genotoxicity induced by metals from orthodontic appliances using micronucleus and comet assays. Genet Mol Res 7:1259-1266, 2008
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32. Bass JK, Fine H, Cisneros GJ: Nickel hypersensitivity in the orthodontic patient. Am J Orthod Dentofac Orthop 103:280-285, 1993 33. Prystowsky SD, Allen AM, Smith RW, et al: Allergic contact hypersensitivity to nickel, neomycin, ethylenediamine, and benzocaine. Relationships between age, sex, history of exposure, and reactivity to standard patch tests and use tests in a general population. Arch Dermatol 115:959-962, 1979 34. Schriver WR, Shereff RH, Domnitz JM, et al: Allergic response to stainless steel wire. Oral Surg Oral Med Oral Pathol 42:578-581, 1976 35. Dunlap CL, Vincent SK, Barker BF: Allergic reaction to orthodontic wire: report of case. J Am Dent Assoc 118:449450, 1989 36. Blanco-Dalmau L, Carrasquillo-Alberty H, Silva-Parra J: A study of nickel allergy. J Prosthet Dent 52:116-119, 1984 37. Goncalves TS, Morganti MA, Campos LC, et al: Allergy to auto-polymerized acrylic resin in an orthodontic patient. Am J Orthod Dentofac Orthop 129:431-435, 2006 38. Stenman E, Bergman M: Hypersensitivity reactions to dental materials in a referred group of patients. Scand J Dent Res 97:76-83, 1989
39. Menezes LM, Campos LC, Quintao CC, et al: Hypersensitivity to metals in orthodontics. Am J Orthod Dentofac Orthop 126:58-64, 2004 40. Menezes LM, Souza FL, Bolognese AM, et al: An allergic reaction to orthodontic appliances: a case report. Southern Brazilian J Orthodontics Facial Orthop 1:51-56, 1997 41. Menezes LMd, Freitas MPM, Gonçalves TS: Biocompatibility of orthodontic materials: myth or reality? Revista Dental Press de Ortodontia e Ortopedia Facial 14:144157, 2009 42. Kusy RP: Clinical response to allergies in patients. Am J Orthod Dentofac Orthop 125:544-547, 2004 43. Barrett RD, Bishara SE, Quinn JK: Biodegradation of orthodontic appliances. Part I. Biodegradation of nickel and chromium in vitro. Am J Orthod Dentofacial Orthop 103:8-14, 1993 44. Sfondrini MF, Cacciafesta V, Maffia E, et al: Chromium release from new stainless steel, recycled and nickel-free orthodontic brackets. Angle Orthod 79:361-367, 2009 45. Eliades T, Trapalis C, Eliades G, et al: Salivary metal levels of orthodontic patients: a novel methodological and analytical approach. Eur J Orthod 25:103-106, 2003
here is increasing concern about the biocompatibility of dental materials1 and, therefore, this topic has been widely investigated during recent years. The metals that are released from biomaterials in various sites of the human body have attracted the interest of many investigators because it is believed that the degradation products can elicit a foreign-body reaction or induce pathologic processes. Particularly in orthodontics, there is interest in investigating reactions secondary to the use of metals that are known allergens.1 Major emphasis has been placed on the levels of nickel and chromium in fluids, such as saliva,2-4 blood,5 or urine.1 However, studies on these issues have given rise to questions without answers, confirming the need to learn more about the biocompatibility of dental materials.2
T
Department of Orthodontics, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. Department of Orthodontics, State University of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil. Address correspondence to Luciane Macedo de Menezes, DDS, MS, PhD, Assistant Professor, Department of Orthodontics, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Av. Ipiranga, 6681—Predio 6, Sala 209, Porto Alegre, Brazil. E-mail: [email protected] © 2010 Elsevier Inc. All rights reserved. 1073-8746/10/1604-0$30.00/0 doi:10.1053/j.sodo.2010.06.006
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Most orthodontic appliances are made from a stainless-steel alloy, containing approximately 6% to 12% nickel and 15% to 22% chromium,6 and, because they are continuously exposed to saliva, the metals must exhibit corrosion resistance.7 All metals and alloys are subject to corrosion. The alloy’s ability to be biocompatible appears to be related to its pattern and mode of corrosion. Corrosion is an electrochemical process that results in the loss of the essential metallic properties of a metal. Metal destruction by corrosion occurs either through loss of metal ions directly into solution or by progressive dissolution of a surface film, typically an oxide or sulfide, on the metal.7 The resulting products might trigger inflammatory responses of the soft tissues and cause irritation or dermatitis.8
The Relationship Between Corrosion and Biocompatibility The resistance to corrosion is a fundamental aspect of biocompatibility and may be affected by several factors, such as the manufacturing process, type of alloy, surface characteristics of the piece,6 environment in which the piece is inserted,9 and use of the alloy (aging).2 Corrosion releases metallic ions into solution, either directly or through dissolution or destruc-
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Release of Ions from Metallic Orthodontic Appliances
tion of surface oxide or other films and, in the clinical setting, such metallic ion release may elicit adverse patient reactions, many of which have been reported in the literature.7 One of the most common reactions is the hypersensitivity to nickel, due to a direct relationship with the presence of this metal in the environment, and may be caused by ingestion or direct contact with the skin and/or mucosa. However, some questions remain to be answered. How much of the corrosion products are actually absorbed by the organism?5 Is the amount of metal released sufficient to sensitize a person or to maintain a reaction in a previously sensitized person?
The Role of Corrosion on the Release of Ions The microstructure of a metal is a basic parameter that affects both its mechanical properties and, in particular, its corrosion behavior. Variations in manufacturing technique and postmanufacturing finishing and polishing operations might affect the corrosion behavior of orthodontic appliances.7,10 Three principal methods are used to manufacture brackets, namely casting, machining or milling, and powder metallurgical (sintering) techniques. Cast and sintered brackets are manufactured in a near-finished condition, but with milled brackets, the slots and wings are machined into lengths of rolled strip that is then cut into individual brackets. With regard to wires, manufacturers are well aware of the susceptibility of orthodontic alloys to the various forms of corrosion and have taken some steps to combat this potentially destructive process: alloy substitution or addition (the addition of certain metals to an alloy can reduce its susceptibility to corrosion), coatings (orthodontic archwires and brackets can be coated with either titanium nitride or an epoxy resin) and modification of the production process. Mechanical or chemical disruption of the protective film, or exposure to a medium that dissolves the film and prevents its reformation, will result in corrosion. Corrosion involves two concomitant reactions, an oxidation reaction at the anode and a reduction reaction at the cathode. Commonly, the anodic reaction will continue until there is total consumption of the metal, unless the metal can form a protective
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surface film (a process known as passivation) or the cathodic reactant is consumed. An alternative and industrially important means of controlling or preventing corrosion is to add to the solution an inhibitor, a substance that reacts with the metal to form a protective film on its surface. Although adding a corrosion inhibitor to the oral environment is generally not possible, there are indications that certain naturally occurring proteins in saliva are corrosion inhibitors. Depending on the thermodynamics and kinetics of the overall reaction, corrosion may proceed slowly or rapidly and occur as a general or localized attack.7 Chromium ions provide an electrochemically formed passive film that offers protection against aggressive ions in the oral environment and prevents corrosion. This effect increases as the chromium content increases. As a result, stainless-steel and chromium-containing alloys do not corrode easily. The mechanism occurs by creating a thin oxide film, which delays corrosion. Integrity of chromium oxide on a metal surface is very important and chromium oxide must be maintained and kept stable throughout the entire material.11 However, when stainless steel is heat-treated or when bends or welds are made in wires, surface oxidation might occur, and an uneven oxide film may cause localized corrosion. Each heat treatment environment and cooling method can affect the thickness and form of the uneven oxide film on the wire surface, which can create various degrees of corrosion. The level of corrosion of any metal and the release of ions depends on the chemistry of the solvent in which it is immersed, the pH of the solution, and the length of immersion. To evaluate some of these parameters (pH value, length of immersion and type of archwire) on release of metal ions from orthodontic appliances, simulated fixed orthodontic appliances were immersed in artificial saliva of different pH values during a 28-day period. Three types of archwires were used: stainless steel, nickel-titanium (NiTi), and thermo NiTi. The quantity of metal ions was determined using a high-resolution mass spectrophotometer. The release of six different metal ions was observed: titanium, chromium, nickel, iron, copper, and zinc. Results showed that the appliances released measurable quantities of all ions examined; the
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change in pH had a very strong effect (up to 100-fold) on the release of ions; and the release of ions was dependent on wire composition, but, it was not proportional to the content of metal in the wire. The largest number of ions was released during the first week of appliance immersion. All three observed parameters (chemical composition of the archwire, pH value of the artificial saliva, and time of exposure to the solution) influenced ion release.12 The greatest release of ions occurred during the first 7 days with a gradual decline thereafter. This finding cannot be ascribed to saturation of the solution with metal ions because the solution was changed for every time period. This kinetics of ion release can be explained by an initial surge of ion release from the metal surface or by formation of a stable oxide layer that slows down further ion release.13 Decreasing the pH from 6.75 to 3.5 increased the release of ions on average 37-fold, with the largest increase for chromium (1:106) and the smallest for titanium (1:7). These results confirm the hypothesis that low pH values reduce the resistance of dental alloys to corrosion.12,14
Metals That Are Released from Orthodontic Appliances The major corrosion products are iron, chromium, and nickel for stainless steel and titanium and nickel for nickel–titanium alloys.11 The oral environment is considered hostile and potentially corrosive.10 Among stainless-steel and nickel– titanium corrosion products nickel and chromium have received the most attention because of their reported adverse effects.11 Nickel is the most common cause of contact allergy15 and is known to trigger more allergic reactions than all other metals combined. In addition to the allergic issue, carcinogenic, mutagenic, and cytotoxic effects have been assigned to nickel and, to a lesser extent, chromium.2 Nickel is not a cumulative toxin; it is absorbed in the gastrointestinal tract and eliminated by its metabolic route.16 The main route for elimination of nickel is through the kidneys; nearly 90% is quickly excreted in urine.17 For patients with no occupational exposure to nickel, the mean urinary nickel level is about 4.5 g/L (range, 1.9-9.6 g/L) or, according to other authors, up to 50 g/L. Nickel can also be eliminated in
saliva and sweat; this might contribute to increased excretion in high-temperature areas.1 Studies have demonstrated that other ions present in the silver solder, such as cadmium, copper, silver, and zinc, may be released in the oral cavity, whose exposure may determine several adverse effects with direct toxic alterations in an acute or chronic manner.18 Such metallic ions are potentially dangerous chemicals, being included in the list of substances and processes that pose high risk to human life because of their carcinogenic potential to the lung, prostate, and kidneys, in addition to alterations in the hematopoietic, urinary, and digestive systems.
Signs of Corrosion of the Orthodontic Appliances The corrosion processes of the orthodontic appliances, when severe, may be observed by the naked eye as a discoloration (change of enamel color around the brackets),19 as the result of the deposition of corrosion products. Furthermore, corrosion is a continuous process, and its effects are cumulative so that in the bracket slot, there may be a progressive increase in surface rugosity or a corrosion product buildup over time. This may cause increased frictional resistance to orthodontic sliding mechanics and adversely affect the progress of treatment.7 Often, the corrosion process may be invisible and quantified only by the concentration of the ions released.
Evaluation of the Ions Released from Orthodontic Appliances There are three ways of investigating metal ion release: in vitro, retrieval (ex vivo investigation of in vivo aged samples), and in vivo.19 Comparisons with in vitro studies are necessary, yet limited, because of variations in methodology, such as the immersion solution. The most frequent solutions used are saline solutions (0.05% or 0.9%) or artificial saliva with different compositions. The storage method may also vary between static and dynamic media according to changes of solution to avoid saturation.2
Release of Ions from Metallic Orthodontic Appliances
In Vitro Study Evaluations and Their Usefulness Several questions are evaluated or answered based on in vitro studies. What are the ions released from orthodontic appliances and amount released? Can the type of alloy used in the fabrication of the brackets have an influence on the quantity of ions released? Is the release pattern of new and recycled brackets the same? Do titanium brackets, one of the alternatives to stainless steel, corrode? Do these brackets release ions? Studies that address some of these issues are listed in Table 1. The quantities of released metal ions measured in some in vitro studies are useful for relative comparisons and for determination of the effect of each individual variable on ions released without the influence of external factors.12 One of the first studies to research this topic was conducted by Park and Shearer in 1983. They verified that the amount of nickel released in vitro by a simulated orthodontic appliance was about 40 g per day.20 Because human dietary intake of nickel is reported to be 300 to 500 g per day,21 the release of 40 g of nickel per day is well below the normal daily intake and may not be of clinical significance.20 To assess whether the type of alloy used in the fabrication of the brackets can have any influence on the quantity of ions released, 2 groups of stainless steel brackets were formed: group A (American Iron and Steel Institute [AISI] 303) and group B (AISI 316 L). The specimens (simulated orthodontic appliances) were put in saline solution (0.05%), in a precision shaking Dubnoff incubator (Precision Scientific Co., Chicago, IL), at 36°C, for 60 days. The ion release was detected by atomic absorption spectrophotometer. The weight of the brackets was also measured before and after the test. The results indicated that group A released more nickel and chromium ions than group B. Moreover, the brackets in group A also presented weight loss, which is considered an indicator of corrosion. It was concluded that, under the study conditions, the brackets from group A presented higher biodegradation than group B brackets, which could be associated with the composition and manufacturing process of these brackets.22 Another issue investigated was the ion release pattern of new and recycled stainless steel brackets. To evaluate it, new and recycled brackets
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were immersed in buffers of different pH values over a 48-week period. The release of nickel, chromium, iron, copper, cobalt, and manganese ions was analyzed by atomic absorption spectophotometry. The results showed that recycled brackets released more ions than new brackets. Brackets immersed in solutions of pH 4 released more ions than those immersed in solutions of pH 7, and the total amount of ions released increased with time over the 48-week period. This study demonstrates that both new and recycled brackets will corrode in the oral environment. It has been suggested that the microstructural changes after recycling, because of the cleaning and sterilization procedures involved, result in an increase in corrosion7 that contraindicates the use of recycling. To avoid clinical side-effects, metal brackets more resistant to corrosion should be made, and recycled brackets should not be used.4 These results were later corroborated and, in some countries, such as the United Kingdom, the practice of recycling is no longer recommended.10 Titanium brackets are of interest because their use is advantageous in the orthodontic treatment of patients with an allergy to nickel and other specific substances. However, in an in vivo investigation, performed by Harzer et al,23 that tested how the surfaces of titanium brackets react to the corrosive influence of acidic fluoride-containing toothpaste during orthodontic treatment, the authors observed that significantly more plaque accumulated, and a more marked change of color occurred on the surface of titanium brackets than on stainless-steel brackets. The surface of the rolled wings of titanium brackets was very rough, and the biocompatibility of titanium supports plaque adherence, serving as a depot for bacteria and electrolytic medium for different ions. The slots of titanium brackets are not as rough as the wings because the slots are milled and not rolled. The manufacturer should modify the production process and mill the entire bracket. Despite this, the researchers comment that titanium brackets can safely be used.23
Important Aspects of In Vivo Studies The administration and elimination routes are important aspects for understanding the reactions to metals.1 Blood, urine, and hair are the most accessible tissues for measurement of ex-
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Table 1. Some Research Regarding the In Vitro Release of Ions From Orthodontic Appliances Author/Year
Study Purpose
Barret, Bishara and Quinn (1993)43
To compare in vitro the corrosion rate of a standard orthodontic appliance
Park and Shearer (1993)20
To evaluate the amount of nickel and chromium released from a simulated appliance To evaluate the release of nickel and chromium from five samples consisting of braces, extraoral and quad-helix
Kerusuo et al (1997)24
Solution/Evaluation Time
Brackets Bands and brackets (AISI 305 and 316) bondable brackets (AISI 303 and 304)
Artificial saliva medium at 37°C days 1, 7, 14, 21, 28
Sodium chloride 0.05% solution
Sodium chloride 0.9% for 2 h, 24 h, and 7 d
Huang et al (2004)4
Compare the release of metal ions from new and recycled brackets
Tomy, Ormco, Dentaurum, 3M Unitek
Artificial saliva (with different pH values over a 48-week period)
Dolci et al (2008)22
To evaluate, in vitro, the biodegradation of simulated orthodontic appliances consisting of stainless steel brackets and wires
Group A (AISI 303); and group B (AISI 316 L).
Saline solution (0.05%), in shake, at 36°C days 7, 14, 28, and 60
Sfondrini et al (2009)44
To test the hypothesis that there is no difference in the amounts of chromium released from new or recycled stainless steel brackets, and nickelfree brackets.
Stainless-steel brackets, stainless-steel recycled brackets and Ni-free brackets
Artificial saliva at various acidities (pH 4.2, 6.5, and 7.6) 15 min, 1 h, 24 h, 48 h, 120 h
posure or dose to a product or substance, and are sometimes mentioned as indicator tissues. Despite this, the most significant method for measurement of nickel release before and after onset of orthodontic treatment is salivary analysis because it is the first diluents of the human
Conclusion Orthodontic appliances release measurable amounts of nickel and chromium when placed in an artificial saliva medium. For both arch wire types, the release for nickel averaged 37 times greater than that for chromium. Release of 40 g of nickel and 36 g of chromium per day.
Detectable release of nickel and chromium from orthodontic appliances seems to occur, and the amount of nickel released increases in dynamic conditions. The authors commented that the amount released may be considered negligible under a toxicologic point of view, but can be of considerable importance for individuals with a high degree of sensitivity to níckel. Recycled brackets released more ions than new brackets. Brackets immersed in solutions of pH 4 released more ions than those immersed in solutions of pH 7, and the total amount of ions released increased with time over the 48-week period. Brackets from group A presented a higher biodegradation than group B brackets, that could be associated to composition and manufacturing process of these brackets. The greatest amount of chromium was released from new stainless-steel brackets. The smallest release was measured with Ni-free brackets. The difference between recycled brackets and Ni-free brackets was not statistically significant. For all brackets, the greatest release was measured at pH 4.2.
body and allows long periods of analyses.19 The warm and moist condition in the mouth offers an ideal environment for the biodegradation of metals, consequently facilitating the release of metals ions that can cause adverse effects. However, there is little qualitative or quantitative
Release of Ions from Metallic Orthodontic Appliances
data available on the release of metals or metallic salts within the oral cavity.11
The Relationship Between Blood, Urine, and Ions Release An important question is whether orthodontic patients accumulate measurable concentrations of nickel in their blood during the initial course of orthodontic therapy. To address this question blood samples were collected at three different times: before the placement of orthodontic appliances, 2 months after their placement, and 4 to 5 months after their placement. The study involved 31 subjects; 18 female and 13 male, between 12 and 38 years of age—all had malocclusions that required the use of a fully banded and bonded edgewise appliance. A total of 93 blood samples (3 from each patient) were analyzed by atomic absorption spectrophotometry. The results obtained from this investigation indicate that orthodontic appliances used, in their “as-received” condition, corrode in the oral environment releasing both nickel and chromium, in amounts significantly below the average dietary intake. Furthermore, the biodegradation of orthodontic appliances during the initial 5 months of treatment did not result in significant or consistent increase in the blood level of nickel.5 The pretreatment and treatment levels of nickel in the urine of 21 orthodontic patients (12 female, 9 male patients) wearing fixed appliances were evaluated. This was done before placement of orthodontic appliances and 2 months after placement. Nickel ion analysis was carried out by the use of atomic absorption spectrophotometry. Urinary nickel levels increased significantly after the placement of orthodontic appliances, for both sexes. The biological effect of a systemic increase in urinary nickel is unknown. Long-term follow-up and larger samples of patients are needed to validate the results and to determinate the implications of these findings.1
Concentrations of Metal Ions Released in Saliva The large variability in ion concentration among subjects is a common finding when the release of metal ions in saliva is examined.24-27 This variation may be related to several factors be-
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cause saliva does not present a constant composition and may be different among individuals or even among periods for the same individual. The physical properties, amount, and composition of saliva are influenced by factors, such as diet, period of the day, and psychic conditions.26 The actual amounts of nickel and chromium released from fixed appliances have been distinct but low, and well below the normal daily intake of nickel in diet. The literature includes some in vivo studies evaluating the ion release in saliva (Table 2). In an effort to understand the issues on ion release and its biological effects, in vivo research was conducted. Saliva from 31 subjects, before the placement of brackets and 3 weeks after placement, was collected. The nickel and iron were quantified by atomic absorption spectroscopy. The only difference observed for the concentration and volume of nickel and iron, was immediately after placement of the appliance, when there was a significant increase. So it seems that there is a high initial release of metals, but this effect decreases with time.26 In 1997, the salivary concentrations of nickel and chromium in patients wearing different types of appliances were evaluated, by Kerosuo et al.24 The study sample was composed of 47 patients, and 4 saliva samples were collected: before placement of the appliance, after 2 days, after 1 week, and after 1 month. The mean salivary concentration was 55 ng/mL for nickel and 61 ng/mL for chromium, similar to the values observed before placement of the appliance.24 The concentration of nickel in the saliva and dental biofilm in young patients, who wore and did not wear fixed orthodontic appliances, was compared. When the saliva samples were taken, the appliances had been in place an average of 16 months in the group who wore the appliances. A significantly greater content of nickel was found in the plaque and saliva of patients with orthodontic appliances (median values for nickel in the saliva were of 25.3 and 14.9 g/g, for patients with and without orthodontic appliances, respectively).28 In another study, the alterations in the chromium and nickel concentrations in the saliva of orthodontic patients treated with fixed orthodontic appliances were evaluated. Forty-five orthodontic patients were included in this study. The first group consisted of 15 patients (7 fe-
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Table 2. Some Research Regarding the In Vivo Release of Ions from Orthodontic Appliances (Saliva) Author/Year
Ions
Sample
Characteristics
Duration
Results
Before insertion of the appliance, 2 d 1 wk and 1 mo Before insertion of the appliance, 1 wk, 1 and 2 mo
No differences before and after appliance. No differences between groups.
Before insertion of the appliance, 1 wk, 1 mo, 1 year, and 2 years
Reached their highest levels in the first mo and decreased to their initial level in the rest of the groups. No differences between groups. Metal levels did not exceed those of daily intake. Increase of ions during treatment.
Kerosuo et al 199724
Chromium, nickel
47 patients
Different types of appliances
Kocaderelli et al, 200025
Chromium, nickel
30 patients (15 control)
Agaoglu et al, 200129
Chromium, nickel
100 patients
Fixed appliance15; fixed appliance in maxillary arch15 Fixed appliance
Eliades et al, 200345
Chromium, nickel, ferrous
17 patients (7 control)
Fixed appliance
Salivary sample obtained at least 15 mo after appliance
Ramadan 200427
Chromium, nickel
20 patients
Fixed appliance in maxillary arch
Fors and Person, 200628 Souza and Menezes, 20082
Nickel
17 patients (24 control) 30 volunteers
Fixed appliance
Initial, 3 and 12 mo and 1 mo after debonding 48 h
Freitas, 200818
Cadmium, copper, zinc, silver
30 patients (30 control)
Petoumenou et al, 20093
Nickel
17 patients
Chromium, nickel, iron
Removable appliance with bonded brackets (AISI 303 and 316 L) Hyrax appliance
Fixed appliance and Ni–Ti archwires
male, 8 male) with fixed appliances placed in their upper and lower arches. The second group consisted of 15 patients (8 female, 7 male) with a fixed appliance placed only in the upper arch. The control group consisted of 15 patients (7 female, 8 male) who were not undergoing orthodontic treatment. Four samples of stimulated saliva were collected from each patient before insertion of the fixed appliance, 1 week after insertion of the appliance, 1 month after insertion of the appliance, and 2 months after insertion of the appliance. The same four samples of saliva were collected from each control patient at the same time intervals as for the fixed-appliance groups. It was observed that there was a large variation in the concentrations of both nickel and chromium in saliva. No significant
Initial, 10 min 24 h, 7, 30 and 60 d after placement of the appliance Initial, 10 min 24 h, 7, 30 and 60 d after placement of the appliance
2-8 wks after placing the wires
Increase of ions in patients with appliance. Increase of chromium and nickel ions. Increase of ions, with high concentrations immediately after placement of the appliance and tendency of regression within the study period. Increase of ions after placement of band and archwire.
differences were found between the nonappliance group and the samples obtained after insertion of the appliances. The results of the study suggest that fixed orthodontic appliances do not significantly affect nickel and chromium concentrations of saliva during the first 2 months of treatment.25 To test the hypothesis that toxic metallic ions present in silver solder used in orthodontics are released in human saliva, 60 subjects were divided into 2 groups (n ⫽ 30, each): control and study (in need of maxillary expansion with the Hyrax appliance). For analysis of the release of metallic ions, saliva samples were collected from each patient at 6 periods. For both groups it consisted of initial, 10 minutes, 24 hours, and 7, 30, and 60 days after placement of the Hyrax
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appliance. The analysis of saliva was performed by atomic absorption spectophotometry in a graphite oven, determining the concentration of cadmium, copper, zinc, and silver ions. The ion concentrations in the control group exhibited low values for cadmium, copper, and zinc, whereas for the silver ion the values did not reach the detection limit. In the study group, all ions presented expressive concentrations at 10 minutes after placement of the appliance, with higher means for copper, with a tendency for reduction after 24 hours. Comparison between groups revealed significant differences for copper (all periods), zinc (10 minutes, 24 hours, and 7 and 30 days), and for cadmium only at 10 minutes. There was a great release of the ions analyzed in the study, with high concentrations measured immediately after placement of the appliance, but with a tendency to regress within the study period.18
appliances were higher in orthodontic patients than in controls and that nickel released from fixed orthodontic appliances could induce DNA damage in oral mucosa cells.30 The differences between the studies of Faccioni et al30 and Westphalen et al,31 regarding the genetic damage, may be explained by the fact that the study conducted by Faccioni et al30 was a cross-sectional study associated with a larger number of patients analyzed using the appliances for a much longer period (2-3 years). The paucity of research in this field and the importance of the issue in health of the orthodontic patients justify further studies with larger samples and long-term follow-up analysis. These strategies will yield valuable data to better understand the genotoxic potential of metals from orthodontic devices, as well as to assess the biological risk to which orthodontic patients may be submitted.31
Genotoxic Effects from the Ions Released in Oral Cavity
Possible Local or Systemic Effects From Ions Release
Although the amount of metals released from orthodontic appliances is significantly below the average dietary intake and does not reach toxic concentrations,25,29 it cannot be excluded that it can be sufficient to induce biological effects in cells from the oral mucosa.30 Westphalen et al31 assessed the genotoxicity effects from orthodontic appliances by carrying out both micronucleus (MN) and comet (CA) assays in a group of 20 healthy patients undergoing orthodontic treatment. The combination of MN and CA assay is recommended because the CA can be used to detect primary DNA damage (reparable) in a short period, whereas the MN assay detects chromosomal damage in a further stage. In the study conducted by Westphalen et al, the time of sampling was 10 days after the placement of the orthodontic appliance for the CA and 20 days later (30 days after appliance placement) for MN assay. The CA results revealed that orthodontic appliances did not induce any genetic damage. The MN assay showed an increase in MN cells 30 days after the placement of the orthodontic appliances.31 By contrast, when the CA was applied in an in vivo study, conducted by Faccioni et al,30 with 55 orthodontic patients and 30 control subjects, it was demonstrated that metallic ions (nickel) released from orthodontic
The introduction of metal ions into the human body is an additional risk to health which may lead to systemic and local effects.5 Hypersensitivity occurs when an adverse reaction follows contact with subtoxic doses of foreign substances. Three mechanisms comprise hypersensitivity reactions: allergy, intolerance, and hyperreactivity.21 Epidemiologic data demonstrate that the number of people with sensitivity to nickel has increased to approximately 20%.15,32 Contact with nickel by susceptible subjects can yield a wide range of hypersensitivity reactions.33 Nickel allergies may comprise extraoral and intraoral reactions though extraoral allergic reactions are more frequent than intraoral reactions. Nickel allergies may comprise intraoral red zones, blisters, and ulcerations, extending to the perioral area, and are referred to as allergic contact mucositis or dermatitis. Intraoral allergic reactions include redness, edema, itching and dryness of the lips and oral mucosa, burning sensations, as well as gingival inflammation. All these reactions are not necessarily limited to the exposure site. Eczematic and urticarial reactions of the face or more distant skin areas can occur with redness, irritation, itching, eczema, soreness, fissuring, and desquamation.21 Occasionally, fever has been reported as a systemic reac-
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tion.34,35 However, much remains to be understood and studied in terms of nickel, such as its release, absorption and reactions.
Evaluation of a Patient for Sensitivity to the Metal Ions Released When there is suspicion of an allergic reaction, the allergen must be determined. Hypersensitivity is usually diagnosed through patient history, clinical findings, and biocompatibility testing (patch tests).36,37 The literature includes some studies in which patch tests were used to evaluate the hypersensitivity reactions to nickel. Prystowsky et al33 evaluated a sample of 1158 adult volunteers and found that 5.8% had a positive reaction to 2.5% nickel sulfate (9% in women and 0.9% in men). There was a strong correlation between pierced ears, ear lesions, and areas of contact with jewelry. Among patients referred for clinical evaluation of contact dermatitis, 11% had a positive reaction to nickel. Blanco-Dalmau et al36 conducted a patch test to 5% nickel sulfate in 403 subjects (121 male, 282 female). The incidence of positive reaction in the study sample was 28.5%, with a remarkable difference between the sexes (31.9% of female subjects, compared with 20.7% of male subjects). Stenman and Bergman38 performed patch tests in 151 patients (119 female, 32 male) with reported hypersensitivity to the components of dental materials or trinkets. Positive response to metals was observed in 42 patients (28% of the sample), whereas reaction to organic components was observed in 7 patients (4.6%). A positive reaction to nickel was found in 21 patients (14%), including 20 women and 1 man. Jones et al17 attempted to determine the incidence of nickel hypersensitivity with patch tests in 100 patients (50 men, 50 women). The authors investigated the relationship between sex, age, and previous report of allergy to jewelry with hypersensitivity to this metal and found alterations in blood pressure, pulse, or temperature among patients with nickel hypersensitivity. Furthermore, by placing a removable appliance, the authors observed that nickel-hypersensitive patients were prone to demonstrate signs of hypersensitivity, at both the area of contact and distant areas. The authors found an incidence of hyper-
sensitivity to nickel with the patch test of 20% for women and 2% for men. Menezes et al39 evaluated hypersensitivity to eight antigens, some of them components of bands and brackets used in orthodontic practice. The tested substances were cobalt chloride, copper sulfate, potassium dichromate, iron sulfate, manganese chloride, molybdenum salt, nickel sulfate, and titanium oxide. They were removed after 48 hours and assessed by a dermatologist at 48 and 72 hours after antigen application. The patch tests were carried out before and 2 months after the placement of fixed orthodontic appliances. Statistically significant positive reactions were observed for nickel sulfate (21.1%), potassium dichromate (21.1%), and manganese chloride, 7.9%; reactions to nickel sulfate had the greatest intensity. No differences were observed between the reactions before and after placement of the orthodontic appliances; this indicates that they did not sensitize the patients or affect their tolerance to these metals during the study period. No statistical difference was observed regarding sex for any evaluated substance, although a greater tendency to positivity to nickel sulfate was observed among female patients and to potassium dichromate in male patients.
Procedures Recommended in Cases of Allergy to Nickel Firstly, good-quality materials should be used so that the effects of corrosion are minimized. The use of recycled brackets should be avoided and the use of alternative products, such as nickelfree, ceramic, polycarbonate, titanium, or goldplated brackets should be considered. When the allergic reactions do appear shortly after the placement of fixed orthodontic appliances, treatment must be discontinued and any appliances containing nickel removed.19,40,41 After healing, treatment should resume using alternative alloys.42
Conclusions Several questions remain unanswered concerning the biological effect of a systemic increase in nickel levels. In addition, there is a lack of information on abnormal accumulation of nickel in specific tissues of the body. The increase of
Release of Ions from Metallic Orthodontic Appliances
nickel in the patients, despite the low amounts in the composition of orthodontic appliances, is not easily explained. The differences in the changes of excretion of these metal ions might be due to differences in corrosion processes, solubility coefficients, or excretion mechanisms. Although increases in metal ion levels have been detected in some studies after placement of orthodontic appliances, the levels are not sufficient to cause alarm; however, additional in vitro and in vivo studies should be performed to clarify these questions and determine safe levels of metallic ions.
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