Wang2015.pdf

JJOD 2449 1–11 journal of dentistry xxx (2015) xxx–xxx

Available online at www.sciencedirect.com

ScienceDirect journal homepage: www.intl.elsevierhealth.com/journals/jden 1 2 3

Review

Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis

4 5 6 7

8 9 10 11

Q1

Yining Wang a,1, Jinxia Gao a,1, Tao Jiang a, Shanshan Liang a, Yi Zhou a,*, Bruce A. Matis b a b

Department of Prosthodontics, School and Hospital of Stomatology, Wuhan University, Wuhan, PR China Indiana University School of Dentistry, Indianapolis, IN, USA

article info

abstract

Article history:

Objectives: This meta-analysis was performed to evaluate the efficacy of potassium nitrate

Received 23 November 2014

and sodium fluoride as desensitizing agents during tooth bleaching treatment.

Received in revised form

Data, sources and study selection: An electronic systematic literature search was conducted in

12 March 2015

Cochrane Center Register of Controlled Trials, MEDLINE (PubMed) and EmBase in April, 2014

Accepted 27 March 2015

in English and without time restrictions. Study information extraction and methodological

Available online xxx

quality assessments were accomplished by two reviewers independently. Methodological quality was assessed by using the ‘‘Criteria for judging risk of bias in the ‘Risk of bias’

Keywords:

assessment tool’’. Dichotomous data was summarized by odds ratio (OR) with 95% confi-

Hydrogen peroxide

dence interval (CI) and continuous data was summarized by mean difference (MD) or

Carbamide peroxide

standardised mean difference (SMD) with 95% confidence interval (CI). Statistical analyses

Tooth bleaching

were carried out by using Review Manager 5.2.

In-office bleaching

For evaluation of percent of patients experiencing tooth sensitivity (POTS), the pooled OR of

At-home bleaching

desensitizers vs. placebo was 0.45 (95% CI: 0.28–0.73, P = 0.29). The pooled SMD of desensitizers

Tooth sensitivity

vs. placebo was 0.47 (95% CI: 0.77 to 0.18, P = 0.13) in evaluation of level of tooth sensitivity

Desensitizing

(LOTS). The results of shade evaluation remained inconsistent by evaluating subjective shade

Potassium nitrate

guide unit difference (DSGU or SGU) and objective colour difference (DE). Conclusions: This meta-analysis was performed to evaluate the efficacy of desensitizing agents, potassium nitrate and sodium fluoride, for tooth bleaching treatments. Potassium Q2 nitrate and sodium fluoride reduce tooth sensitivity while no consistent conclusion of tooth colour change was found. # 2015 Published by Elsevier Ltd.

14 13 15

12

* Corresponding author at: Department of Prosthodontics, School and Hospital of Stomatology, Wuhan University, 237# Luo Yu Road, Wuhan 430079, PR China. Tel.: +86 27 87646696; fax: +86 27 87873260. E-mail address: [email protected] (Y. Zhou). 1 These authors contributed to the work equally and should be regarded as co-first authors. http://dx.doi.org/10.1016/j.jdent.2015.03.015 0300-5712/# 2015 Published by Elsevier Ltd.

Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

JJOD 2449 1–11

2

16 17

18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74

journal of dentistry xxx (2015) xxx–xxx

1.

Introduction

Q3 Following improvement in the economy and in people’s living

standards, an increasing number of people became self-aware that teeth play an important role in their appearance. These patients with discoloured teeth demand whiter teeth and a more aesthetically pleasing smile. According to a previous review, teeth whitening may be improved by physical or chemical approaches.1 When comparing whitening toothpastes, professional cleaning, microabrasion of enamel with abrasives and acid, resin-bonded composites, porcelain veneers and crowns, tooth bleaching was considered a more accepted and conservative approach to improving the colour of teeth and a pleasant smile.1–6 The main chemical approaches of tooth bleaching include at-home treatment, in-office procedure and bleaching with over-the-counter (OTC) bleaching products.7,8 For at-home tooth bleaching treatment, 10% carbamide peroxide (CP) delivered in a custom-fitting mouth tray was introduced by Klusmier in late 1960s.9 This successful technique was published by Haywood and Heymann in 1989 and has become the gold-standard treatment in tooth whitening.9–12 Later the in-office procedure, of applying a high concentration of hydrogen peroxide (HP) to tooth bleaching with (or without) exposure to various kinds of heat or curing lights to enhance the effects became popular.8,11–15 Typically a 30–35% concentration of HP is used in vital and nonvital tooth bleaching during in-office procedures.11 Unlike at-home bleaching techniques, in-office bleaching is supervised by dentists. OTC products have increased in popularity with patients and are self-administered. Different OTC products have become available in markets, including whitening strips and gels, whitening rinses, paint-on gels with brushes, toothpastes, etc.1,8,16 The safety and efficacy of OTC products remain questionable.1,8,16,17 Evidence has shown that bleaching products based on CP and/or HP are relatively safe and effective when following manufacturer’s instructions.1,7,18 Nevertheless adverse effects are another concern often expressed with bleaching.19–21 Many publications have voiced concerns about oral health and potential tooth structure change after bleaching. Difficulty in dental hygiene, an unpleasant sensation in the mouth, gingival irritation, during and postoperative tooth sensitivity, structural integrity of dental hard tissue and restoration are common risks reported with tooth bleaching.20,22–24 Tooth sensitivity and/or gingival irritation may be typical side effects associated with tooth bleaching techniques.25 In previous reports, up to 66% of patients experienced side effects (tooth sensitivity and/or gingival irritation) after overnight vital bleaching.26 This kind of discomfort is sometimes responsible for patients’ hesitancy in tooth bleaching. Modifications and improvements have been made to bleaching products. As compared with decreasing the concentration of peroxide products and administration of analgesic, the application of a desensitizing agent seemed to be an effective option to reduce tooth sensitivity.27–29 Potassium nitrate and sodium fluoride as desensitizers are used widely to treat tooth sensitivity. These agents may be contained in bleaching gel and delivered by using a custom

tray during treatment. Other delivery systems can be used independently by placing them into a subject’s mouth for a short time before bleaching is introduced.4,29–32 The mechanism of action of potassium nitrate remains unknown. Several randomized clinical trials have been published assessing the safety and efficacy of tooth bleaching treatments. Some of them conclude that desensitizers based on potassium nitrate and sodium fluoride reduce tooth sensitivity.29,31–34 Others question the efficacy of tooth bleaching when a desensitizing agent is used.4,30 The results of these studies are sometimes even conflicting, possibly because of the small number of patients. Therefore the aim of this meta-analysis is to provide a more accurate estimate of the efficacy of two desensitizing agents, potassium nitrate and sodium fluoride, during bleaching treatment.

75 76 77 78 79 80 81 82 83 84 85 86 87 88 89

2.

90

Methods

All the work was performed by two reviewers, independently. A discussion ensued if any disagreement occurred and unresolved issues were solved by consulting a third reviewer.

91 92 93

2.1.

94

Inclusion criteria

Clinical studies were included in this meta-analysis that satisfied the following inclusion criteria. Participants: patients with discoloured teeth (intrinsic discolouration and/or extrinsic discolouration) undergoing tooth bleaching treatment had to be randomized to test or control groups. The main approaches of tooth bleaching had to include at-home treatments and/or in-office procedures. Interventions: desensitizer agents had to be based on potassium nitrate and/or sodium fluoride intervention products. Comparisons: control products had to be placebo or other desensitizing agents. Outcomes: outcomes had to be arranged into two categories: tooth sensitivity evaluation and shade evaluation. Studies design: studies had to be designed as randomized controlled trials (RCT) or controlled clinical trials (CCT).

95 96 97 98 99 100 101 102 103 104 105 106 107 108

2.2.

109

Exclusion criteria

Clinical studies were excluded in this meta-analysis that contained the following criteria: (1) those estimating the efficacy of over-the-counter (OTC) products which contained desensitizing components, such as dentifrice, whitening strips; (2) duplicate studies; (3) irrelevant studies; (4) in vitro studies.

110 111 112 113 114 115

2.3.

116

Search strategy and study selection

An electronic systematic literature search was conducted in Cochrane Center Register of Controlled Trials, MEDLINE (PubMed) and EmBase in April, 2014 in English and without time restrictions. Additional studies were identified by searching reference lists of included studies and contacting experts. The medical subject headings (MeSH) and text words ‘‘hydrogen peroxide’’, ‘‘carbamide peroxide’’, ‘‘whitening’’, ‘‘tooth whitening’’, ‘‘bleaching’’, ‘‘tooth bleaching’’, ‘‘brightening’’, ‘‘aesthetics’’,

Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

117 118 119 120 121 122 123 124

JJOD 2449 1–11 journal of dentistry xxx (2015) xxx–xxx

125 126 127 128 129 130 131 132 133 134

‘‘in-office bleaching’’, ‘‘at-home bleaching’’, ‘‘tooth sensitivity’’, ‘‘hypersensitivity’’, ‘‘sensitivity’’ ‘‘desensitizing’’, ‘‘desensitizer’’, ‘‘desensitizing agent’’, ‘‘potassium nitrate’’, ‘‘potassium nitrate–fluoride’’, ‘‘fluoride gel’’ were used and in combination with other strategies to identify RCTs or CCTs. Initial scanning of the retrieved studies was conducted on the basis of the titles and abstracts. The duplicated and obviously irrelevant studies were removed. Full texts of potential interests were then scanned and only those meeting inclusion criteria were included.

135 136

2.4. Assessment of methodological quality and data extraction

137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156

Quality of retrieved studies was assessed by using the ‘‘Criteria for judging risk of bias in the ‘Risk of bias’ assessment tool’’. It was a domain-based evaluation, which was neither a scale nor a checklist.35 In this assessment tool, random sequence generation, allocations concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting and other bias were designed to appraise the methodological quality of included studies. Bias was judged in each study as ‘‘low risk of bias’’, ‘‘high risk of bias’’ and ‘‘unclear risk of bias’’. Low risks of bias for each important outcome within and across studies were unlikely to seriously alter the results. While for the summary assessments of one or more unclear risk of bias, it would raise some doubt about the results. In addition, the summary assessments for one or more of the high risk of bias would seriously weaken confidence in the results. Extracted data included first author, year of publication, publication country, number of participants, desensitizing agents, bleaching approach and material and outcome reporting.

157

2.5.

158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180

Statistical analysis was performed following the Cochrane Handbook for Systematic Reviews of Interventions.35 A meta-analysis of RCTs or CCTs was conducted to estimate the efficacy of desensitizer agents, potassium nitrate and sodium fluoride, for tooth bleaching treatment. Data type for the outcome measurement included dichotomous data and continuous data. Dichotomous data in percent of patients experiencing tooth sensitivity (POTS) was summarized by odds ratio (OR) with 95% confidence interval (CI). Continuous data in level of tooth sensitivity (LOTS), subjective shade guide unit difference (DSGU or SGU) and objective colour difference (DE) were summarized by mean difference (MD) with a 95% CI. If the measurement instruments of the same outcome differed in those included studies, then standardized mean difference (SMD) was used instead of mean difference (MD). The heterogeneity across studies was tested by Cochran’s Q statistic and P-value. P-value lower than 0.10 is an indicator of significant heterogeneity.36,37 In addition, I2 was used to estimate the degree of inconsistency of statistical analysis. The new quantity I2 was ranged from 0% to 100% and 25%, 50%, 75% represented low, moderate and high heterogeneity respectively.37 Fixed effects model was used initially, assuming that all the included studies shared good homogeneity. If

Statistical analysis

3

the heterogeneity was high and the P-value was lower than 0.10, the DerSimonian and Laird random effects model was chosen for meta-analysis.38 Sensitivity analysis was performed by sequentially excluding some studies with high risk of bias in this review. Publication bias was investigated by use of Begg’s funnel plots, which through constructing a funnel plot and examining its signs of asymmetry was able to determine whether the publication bias affected the validity of the estimates.39–41 The signs of asymmetry in a funnel plot suggested the presence of publication bias, but publication bias was not the only reason for the asymmetry. Due to small number of included studies, the analysis of funnel plots and explanation of publication bias would not be described any more. Review Manager 5.2 (The Nordic Cochrane Centre, Cochrane Collaboration) was used to carry out statistical analyses. Thomson Reuters EndNote X7 as the reference manager was used to find and share research in this review.

3.

Results

3.1.

Results of the search and selection of studies

181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200

A total of seven hundred twenty two studies were identified initially based on the search strategy. Two hundred fifty three duplicated studies were removed by using the reference manager EndNote. Another four hundred forty seven obviously irrelevant studies were removed after scanning of the retrieved studies on the basis of the titles and abstracts. For the twenty two studies of potential interests, eight studies were not RCTs/CCTs,30,34,42–47 the desensitizers were GLUMA and VivaSens in two studies,48,49 one study was without available data.50 It was worth mentioning that one study met the inclusion criteria while the full-text could not be found through various ways. This study was not included in the meta-analysis for no data could be abstracted.51 Ten studies were included in this review.4,29,31–33,52–56 A detailed flow chart of retrieval of studies is presented in Fig. 1.

201 202 203 204 205 206 207 208 209 210 211 212 213 214 215

3.2.

216

Characteristics of the included studies

Detailed descriptions of the characteristics about the ten included studies are listed in Table 1. The studies included were accomplished in Brazil, USA, Italy, Jordan and Spain. The publication year of those studies range from 2004 to 2014. A total of three hundred ninety four patients were included in those ten studies and the sample size of each study ranged from 20 to 40 patients. Only one study was a multicentre trial and contained ninety one patients.53 Carbamide peroxide (CP), as the at-home bleaching agent, was used in five studies,31,52– 55 while hydrogen peroxide (HP) was used as the agent with inoffice bleaching in five studies.4,29,32,33,56 The percentage of carbamide peroxide (CP) was 10% in three studies,31,53,55 16% in one study,52 30% in one study.54 Four studies targeted 35% hydrogen peroxide (HP) as the bleaching agent.29,32,33,56 One study used 28% hydrogen peroxide (HP).4 Potassium nitrate with sodium fluoride as the desensitizing agents were used in six studies.29,31–33,53,55 Two studies used only potassium nitrate4,54 and two studies used only sodium fluoride52,56 as

Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234

JJOD 2449 1–11

4

journal of dentistry xxx (2015) xxx–xxx

Fig. 1 – Flow chart of retrieve studies.

235 236 237 238 239 240

the desensitizer. The POTS, LOTS, DSGU or SGU and DE were reported in one or more in the included studies. Two studies reported median and interquartiles ranges of LOTS. Data conversion was not performed in this review due to the small sample size.29,32 The duration of intervention and follow-up varied between one week and six months.

241

3.3.

242 243 244

The results of the methodological quality assessment of the ten RCTs are presented in Figs. 2 and 3. All of the judgements in a cross-tabulation of the study by entry were presented in

Q6

Assessment of methodological quality

Fig. 2. All of the items in one study were judged as ‘‘low risk of bias’’,29 seven studies were judged as ‘‘unclear risk of bias’’,31,52–54,56 and two studies were judged as ‘‘high risk of bias’’.4,55 Fig. 3 illustrates the proportion of studies with each of the judgements for each entry. The risk of bias of selective reporting was judged as ‘‘low’’, while random sequence generation, allocations concealment, blinding of participants and personnel, blinding of outcome assessment were judged as ‘‘unclear’’. The risk of bias of incomplete outcome data and other bias were judged as ‘‘high’’, however the proportion was so small that it would not seriously weaken confidence in the results.

Table 1 – Characteristics of the included studies. No. of participants

Country

Bleaching agent

Desensitizer

Bleaching approach

Outcome report

Duration of follow-up time

Armenio (2008) Bonafe (2013) Browning et al.53

Total: n = 30 Total: n = 30 Total: n = ?

Brazil Brazil USA

16% CP 35% HP 10% CP

HB OB HB

LOTS; POTS;DSGU LOTS; POTS; DSGU; DE POTS; SGU

>7 weeks >6 months >13 weeks

Gallo et a.54 Leonard et al.55 Maghaireh et al.56 Navarra (2013) Pale (2013) Reis et al.51 Tay et al.33

Total: Total: Total: Total: Total: Total: Total:

USA USA Jordan Italy Spain Brazil Brazil

30% 10% 35% 10% 28% 35% 35%

1.23% SF 5% PN and 2% SF Exp1:0.00% PN and 0.00% SF Exp2: 3.00% PN and 0.00% SF Exp3: 0.50% PN and 0.00% SF Exp4: 0.50% PN and 0.25% SF 5% PN 3% PN and 0.11% SF 2% SF PN and SF 5% PN 5% PN and 2% SF 5% PN and 2% SF

HB HB OB HB OB OB OB

LOTS; POTS LOTS; LOTS; LOTS; POTS; POTS;

>10 days >2 weeks >2 weeks 14 days >3 months >2 weeks >2 weeks

Studies

n = 40 n = 40 n = 51 n = 20 n = 32 n = 30 n = 30

CP CP HP CP HP HP HP

SGU DSGU DE DE LOTS; DSGU LOTS; DSGU

PN, potassium nitrate; SF, sodium fluoride; CP, carbamide peroxide; HP, hydrogen peroxide; HB, at-home bleaching; OB, in-office bleaching; tooth sensitivity: POTS, percentage of patients with tooth sensitivity; LOTS, level of tooth sensitivity. Shade evaluation: DSGU (SGU), visual subject methods; DE, instrumental object measurements.

Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

245 246 247 248 249 250 251 252 253 254 255 256

JJOD 2449 1–11 journal of dentistry xxx (2015) xxx–xxx

5

Fig. 2 – Risk of bias summary: judgements about each risk of bias item for each included study.

257

3.4.

Meta-analysis

3.4.1.

Primary outcomes

258 259 260 261 262 263

Tooth sensitivity evaluation includes POTS and LOTS. POTS was determined at any time during or immediately after tooth bleaching (Fig. 4). LOTS was recorded by using a visual scale. LOTS was evaluated during or up to 24 h after bleaching (24 h) (Fig. 5).

264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282

3.4.2.

Secondary outcomes

Shade evaluation includes DSGU (or SGU) and DE. Tooth colour was evaluated visually by using Vita Classic Shade Guide or Trubyte Bioform Colour Ordered Shade Guide System. DSGU represents the change in number of shade guide units (SGU) (Figs. 6–8). Shade evaluation was also performed by object measurements using a colorimeter or spectrophotometer. The evaluation of DSGU (or SGU) was performed at one week, two weeks and seven weeks after tooth bleaching treatment, respectively. The colour system was based on the following values: L*a*b*. In this system, L* represents the value from black to white, a* represents the measurement along the red– green axis and b* represents the measurement along the yellow–blue axis. A total colour difference between the two colours (DE) was calculated by using the formula: D E = ((DL*)2 + (Da*)2+(Db*)2)1/2 (Fig. 9).29,31 DE was recorded one week after tooth bleaching. The evaluation of POTS is illustrated in Fig. 4. This metaanalysis includes six studies and eleven results. The pooled odds

ratio (OR) of desensitizers vs. placebo was 0.45 (95% CI: 0.28–0.73) while the heterogeneity was I2 = 16% and P-value = 0.29. Statistical analysis in this group showed desensitizers significant in reducing the POTS during tooth bleaching treatment. The evaluation of LOTS is illustrated in Fig. 5. This metaanalysis includes six studies. The pooled SMD of desensitizer vs. placebo was 0.47 (95% CI: 0.77 to 0.18, P = 0.13). Statistical analysis in this group showed desensitizers were significant in reducing the LOTS during or immediately after tooth bleaching. The evaluation of DSGU (or SGU) at one week is illustrated in Fig. 6. The result of pooled SMD of desensitizer vs. placebo was 0.24 (95% CI: 0.03–0.46, P = 0.73) at one week after bleaching. Fig. 7 showed the pooled SMD of desensitizers vs. placebo was 0.34 (95% CI: 0.08–0.60, P = 0.36) two weeks after bleaching. Statistical analysis showed desensitizers had a significant difference in changing tooth colour at one and two weeks after bleaching. Tooth colour change was bigger in experimental groups when compared to control groups. The evaluation of DSGU (or SGU) at seven weeks after bleaching was 0.14 (95% CI: 0.27 to 0.54, P = 0.06) (Fig. 8). Statistical analysis in this group showed desensitizers had no significant difference in changing tooth colour in the long term. The tooth shade evaluation of DE is illustrated in Fig. 9. This meta-analysis included two studies. The SMD for DE was 0.03 (95% CI: 1.08 to 1.14, P = 0.05). Statistical analysis in this group showed desensitizers had no significant difference in changing tooth colour at one week after bleaching.

Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 308 309 310

JJOD 2449 1–11

6

journal of dentistry xxx (2015) xxx–xxx

Fig. 3 – Risk of bias graph: judgements about each risk of bias item presented as percentages across all included studies.

311

3.5. 312 313 314

Sensitivity analysis and publication bias

Sensitivity analysis was performed in both tooth sensitivity and shade change evaluation by sequentially excluding three studies.29,53,55 One study was a multi-centre trial and reported

more than one result.53 Another study also varied in data type.29 The risk of bias was high in the third study.55 Outcome of sensitivity analysis is illustrated in Table 2. When compared to the primary and secondary outcome, statistical analysis remained stable and reliable.

Fig. 4 – Forest plot of comparison: tooth sensitivity, outcome: POTS: percentage of patients with tooth sensitivity. POTS was evaluated during or immediately after bleaching (=24 h). Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

315 316 317 318 319

JJOD 2449 1–11 journal of dentistry xxx (2015) xxx–xxx

7

Fig. 5 – Forest plot of comparison: tooth sensitivity, outcome: LOTS: level of tooth sensitivity. LOTS was evaluated during or immediately after bleaching (=24 h).

320

321 322 323 324 325 326 327

4.

Discussion

This is the first systematic literature review of RCTs or CCTs of desensitizer agents, potassium nitrate and sodium fluoride, in the treatment of tooth bleaching. This meta-analysis of ten RCTs or CCTs has high internal validity. But there are limitations when considering external applicability. Limitations in the design and implementation of some included studies suggest the likelihood of bias. In this

review, three RCTs were performed in USA and another four RCTs were in Brazil; the results may be influenced by context and culture. Potassium nitrate and sodium fluoride as intervention agents vary in concentration and categories of available studies. Carbamide peroxide or hydrogen peroxide is the main materials currently used in at-home or in-office bleaching process and they vary in concentration. Outcome reporting, duration of intervention and follow-up periods also vary. In addition, the data was reported in percentage, which was transformed to dichotomous data when considering POTS

Fig. 6 – Forest plot of comparison: visual shade guide unit evaluation: DSGU (or SGU). DSGU (or SGU) was evaluated one week after bleaching. Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

328 329 330 331 332 333 334 335 336 337

JJOD 2449 1–11

8

journal of dentistry xxx (2015) xxx–xxx

Fig. 7 – Forest plot of comparison: visual shade guide unit evaluation: DSGU (or SGU). DSGU (or SGU) was evaluated two weeks after bleaching.

338 339 340 341 342 343 344 345 346

analysis in one study.53 Finally, though a comprehensive retrieval was conducted in the Cochrane Centre Register of Controlled Trials, MEDLINE (PubMed) and EmBase, there is a possibility of missing studies from other databases. These potential limitations are likely to lower the confidence in the estimate of efficacy and safety of desensitizers. The mechanism of bleaching agents based on peroxide is not well known currently. Initial diffusion of peroxide through enamel and dentine into the pulp chamber is well elucidated

in available literature.2,57 This process may result in pulp inflammation and intradental nerve activity.58 About 50% of the patients experience sensitivity after bleaching, however the mechanism of nociceptor activation is not well understood.59 Tooth sensitivity and pain related to bleaching should be distinguished from dentine sensitivity. Investigators have hypothesized that some degree of pulpal inflammation may accompany bleaching sensitivity, which is different from the hydrodynamic theory in dentine sensitivity.22,60 Tooth bleaching

Fig. 8 – Forest plot of comparison: visual shade guide evaluation: DSGU (or SGU). DSGU (or SGU) was evaluated seven weeks after bleaching. Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

347 348 349 350 351 352 353 354 355

JJOD 2449 1–11

9

journal of dentistry xxx (2015) xxx–xxx

Fig. 9 – Forest plot of comparison: objective colour change evaluation: DE. DE was evaluated one week after bleaching.

356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381

may cause the release of cell-derived factors, such as ATP and prostaglandins. This interaction may excite or sensitize pulpal nociceptors and result in pulp tissue damage.32 Hydrodynamics of intradental nerve activation and neuropeptide release in response to this procedure is another hypothesis which is not well understood currently.22,61 The exact mechanism of action of potassium nitrate and sodium fluoride for reducing tooth sensitivity in the tooth bleaching process is not well understood. It is likely that potassium ions are the active component and potassium nitrate works by reducing dentinal sensory nerve activity due to the depolarizing activity of the K+.34,62–64 On the other hand, fluoride treats tooth sensitivity probable by blocking exposed dentinal tubules or reducing the fluid flow into the pulp and blocking transmission of stimuli.63,65 Some concern has been expressed about the efficacy of desensitizing agents during tooth bleaching treatments. Some studies showed the use of potassium nitrate and/or sodium fluoride have reduced the intensity of tooth sensitivity. The efficacy of tooth bleaching is not affected by this procedure.29,34,52–54 Different results have been noted in other studies, where the percentage and level of tooth sensitivity was similar in both desensitizing agents and placebo cells.51 The efficacy and safety of desensitizing agent in tooth bleaching may relate to various factors; most of them remain unknown. A previous clinical investigation compared the efficacy of 3% potassium nitrate and 0.5% potassium nitrate in

tooth bleaching based on using the same bleaching agent. The result was that 0.5% potassium nitrate significantly reduced the number of days participants experienced sensitivity while 3% potassium nitrate did not.53 A possible explanation may be that 3% potassium nitrate created a higher osmotic gradient than 0.5% potassium nitrate, which increased fluid flow outward and stimulated the mechano-receptors and pain rather than driving sufficient potassium ions inward to reduce pain.53 However, most of the current studies aimed to evaluate the efficacy of using potassium nitrate and/or sodium fluoride in desensitizing agents based on sodium fluoride are rare.52 It is worthy to mention that potassium nitrate with sodium fluoride and potassium nitrate alone were usually applied before tooth bleaching while sodium fluoride was usually applied only after patients experienced tooth sensitivity. 52 Sodium fluoride may inhibit demineralization by forming a calcium fluoride layer on enamel. 66 The delivery method of desensitizing agents was different in most of the included studies. Some studies applied desensitizing gel on the buccal surface of participant without disturbing it for ten minutes. 29,32,33 Meanwhile desensitizing agents were contained in the bleaching gel in some of the other studies. 31,54 So the proper concentration, category and delivery method of desensitizing agents should be investigated in a future study. Some guidelines may be helpful in future research and clinical procedures. First, clinicians should inform their patients about the advantages and possible adverse effects of tooth bleaching.14 Second, it is necessary for clinicians to have a full understanding of indications and contraindications of tooth bleaching. For instance, patients with crack tooth syndrome or who experience tooth sensitivity should be counselled when considering tooth bleaching.7 Third, concentration of bleaching agent and application duration may be the key factors in determining tooth bleaching efficacy. A higher concentration of peroxide containing products may enhance the bleaching outcome and reduce the duration of application while side effects may also accompany this kind of procedure. Tooth sensitivity, tooth structure change are potential adverse effects related to higher concentrations of peroxide contained products.67,68 In-office procedures with higher concentration of peroxide containing products should be used with caution.

Table 2 – Tooth sensitivity analysis. Outcome

Excluded Studies

Studies

Participants

POTS

Bonafe (2013) Browning et al.53 Leonard et al.55 None

7 8 10 11

240 249 320 360

Odds Odds Odds Odds

(D)SGU1

Bonafe (2013) Browning et al.53 None

8 7 10

274 223 334

Std. mean difference (IV, fixed, 95% CI) Std. mean difference (IV, fixed, 95% CI) Std. mean difference (IV, fixed, 95% CI)

0.31 [0.07, 0.55] 0.18 [ 0.08, 0.45] 0.24 [0.03, 0.46]

(D)SGU2

Browning et al.53 None

4 7

123 234

Std. mean difference (IV, fixed, 95% CI) Std. mean difference (IV, fixed, 95% CI)

0.22 [ 0.14, 0.58] 0.34 [0.08, 0.60]

(D)SGU7

Bonafe (2013) Browning et al.53 None

4 3 6

140 89 200

Std. mean difference (IV, random, 95% CI) Std. mean difference (IV, random, 95% CI) Std. mean difference (IV, random, 95% CI)

0.18 [ 0.39, 0.74] 0.33 [ 0.34, 1.00] 0.14 [ 0.27, 0.54]

ratio ratio ratio ratio

Statistical method

Effect estimate

(M-H, (M-H, (M-H, (M-H,

0.40 0.33 0.51 0.45

fixed, fixed, fixed, fixed,

95% 95% 95% 95%

CI) CI) CI) CI)

[0.22, [0.17, [0.30, [0.28,

0.71] 0.62] 0.86] 0.73]

Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424

JJOD 2449 1–11

10

425

5.

journal of dentistry xxx (2015) xxx–xxx

Conclusion 21.

This meta-analysis was performed to evaluate the efficacy of desensitizing agents, potassium nitrate and sodium fluoride, for tooth bleaching treatments. Potassium nitrate and/or sodium fluoride reduce tooth sensitivity while no consistent conclusion of tooth colour change was found by using those desensitizing agents.

426 427 428 429 430 431

432

23.

24.

references 25.

Q4

433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 484 485

22.

1. Carey CM. Whitening: what we now know. The Journal of Evidence-Based Dental Practice 2014;14:70–6. 2. Joiner A. The bleaching of teeth: a review of the literature. Journal of Dentistry 2006;34:412–9. 3. Joiner A. Whitening toothpastes: a review of the literature. Journal of Dentistry 2010;38:17–24. 4. Pale´ M, Mayoral JR, Llopis J, Valle`s M, Basilio J, Roig M. Q5 Evaluation of the effectiveness of an in-office bleaching system and the effect of potassium nitrate as a desensitizing agent. Odontology 2013. [Epub ahead of print]. 5. Griffiths CE, Bailey JR, Jarad FD, Youngson CC. An investigation into most effective method of treating stained teeth: an in vitro study. Journal of Dentistry 2008;36:54–62. 6. Bello A, Jarvis RH. A review of esthetic alternatives for the restoration of anterior teeth. The Journal of Prosthetic Dentistry 1997;78:437–40. 7. Sulieman MA. An overview of tooth-bleaching techniques: chemistry, safety and efficacy. Periodontology 2000 2008;48:148–69. 8. Marshall K, Berry TG, Woolum J. Teeth whitening: current status. Compendium of Continuing Education in Dentistry 2010;31:486–95. 9. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence International 1989;20:173–6. 10. Haywood VB. Overview and status of mouthguard bleaching. Journal of Esthetic Dentistry 1991;3:157–61. 11. Haywood VB. History, safety, and effectiveness of current bleaching techniques and applications of the nightguard vital bleaching technique. Quintessence International 1992;23:471–88. 12. Haywood VB. Current status of nightguard vital bleaching. Compendium of Continuing Education in Dentistry 2000:S10–7. quiz S48. 13. Buchalla W, Attin T. External bleaching therapy with activation by heat, light or laser – a systematic review. Dental Materials 2007;23:586–96. 14. Alqahtani MQ. Tooth-bleaching procedures and their controversial effects: a literature review. The Saudi Dental Journal 2014;26:33–46. 15. Sulieman M. An overview of bleaching techniques: 3. Insurgery or power bleaching. Dental Update 2005;32:101–4. 107–108. 16. Demarco FF, Meireles SS, Masotti AS. Over-the-counter whitening agents: a concise review. Brazilian Oral Research 2009;23:64–70. 17. Kugel G. Over-the-counter tooth-whitening systems. Compendium of Continuing Education in Dentistry 2003;24:376–82. 18. Haywood VB, Heymann HO. Nightguard vital bleaching: how safe is it? Quintessence International 1991;22:515–23. 19. Li Y. Safety controversies in tooth bleaching. Dental Clinics of North America 2011;55:255–63. ´ ., Santos 20. Meireles SS, Goettems ML, Dantas RV, Della Bona A IS, Demarco FF. Changes in oral health related quality of life

26.

27.

28.

29.

30.

31.

32.

33.

34.

35.

36. 37.

38. 39.

40.

41.

after dental bleaching in a double-blind randomized clinical trial. Journal of Dentistry 2014;42:114–21. Glickman GN, Frysh H, Baker FL. Adverse response to vital bleaching. Journal of Endodontics 1992;18:351–4. Markowitz K. Pretty painful: why does tooth bleaching hurt? Medical Hypotheses 2010;74:835–40. Yu H, Li Q, Wang YN, Cheng H. Effects of temperature and in-office bleaching agents on surface and subsurface properties of aesthetic restorative materials. Journal of Dentistry 2013;41:1290–6. Dahl JE, Pallesen U. Tooth bleaching – a critical review of the biological aspects. Critical Reviews in Oral Biology and Medicine 2003;14:292–304. Leonard Jr RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and gingival irritation associated with nightguard vital bleaching. Quintessence International 1997;28:527–34. Haywood VB, Leonard RH, Nelson CF, Brunson WD. Effectiveness, side effects and long-term status of nightguard vital bleaching. Journal of the American Dental Association 1994;125:1219–26. Charakorn P, Cabanilla LL, Wagner WC, Foong WC, Shaheen J, Pregitzer R, et al. The effect of preoperative ibuprofen on tooth sensitivity caused by in-office bleaching. Operative Dentistry 2009;34:131–5. Paula E, Kossatz S, Fernandes D, Loguercio A, Reis A. The effect of perioperative Ibuprofen use on tooth sensitivity caused by in-office bleaching. Operative Dentistry 2013;38:601–8. Bonafe´ E, Loguercio AD, Reis A, Kossatz S. Effectiveness of a desensitizing agent before in-office tooth bleaching in restored teeth. Clinical Oral Investigations 2014;18:839–45. Matis BA, Cochran MA, Eckert GJ, Matis JI. In vivo study of two carbamide peroxide gels with different desensitizing agents. Operative Dentistry 2007;32:549–55. Navarra CO, Reda B, Diolosa` M, Casula I, Di Lenarda R, Breschi L, et al. The effects of two 10% carbamide peroxide nightguard bleaching agents, with and without desensitizer, on enamel and sensitivity: an in vivo study. International Journal of Dental Hygiene 2014;12:115–20. Reis A, Dalanhol AP, Cunha TS, Kossatz S, Loguercio AD. Assessment of tooth sensitivity using a desensitizer before light-activated bleaching. Operative Dentistry 2011;36:12–7. Tay LY, Kose C, Loguercio AD, Reis A. Assessing the effect of a desensitizing agent used before in-office tooth bleaching. Journal of the American Dental Association 2009;140:1245–51. Haywood VB, Caughman WF, Frazier KB, Myers ML. Tray delivery of potassium nitrate–fluoride to reduce bleaching sensitivity. Quintessence International 2001;32:105–9. Julian PT, Higgins SG. Cochrane handbook for systematic reviews of interventions version 5.1.0. 2011http://handbook. cochrane.org/. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Statistics in Medicine 2002;21:1539–58. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. British Medical Journal 2003;327:557–60. DerSimonian R, Laird N. Meta-analysis in clinical trials. Controlled Clinical Trials 1986;7:177–88. Begg CB, Berlin JA. Publication bias and dissemination of clinical research. Journal of the National Cancer Institute 1989;81:107–15. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. British Medical Journal 1997;315:629–34. Begg CB. A comparison of methods to detect publication bias in meta-analysis by P. Macaskill, S.D. Walter and L. Irwig. Statistics in Medicine 2002;21:1803. author reply 1804.

Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015

486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554

JJOD 2449 1–11 journal of dentistry xxx (2015) xxx–xxx

555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600

42. Alonso de la Pen˜a V, Balboa Cabrita O. Comparison of the clinical efficacy and safety of carbamide peroxide and hydrogen peroxide in at-home bleaching gels. Quintessence International 2006;37:551–6. 43. Basting RT, Amaral FL, Franc¸a FM, Flo´rio FM. Clinical comparative study of the effectiveness of and tooth sensitivity to 10% and 20% carbamide peroxide home-use and 35% and 38% hydrogen peroxide in-office bleaching materials containing desensitizing agents. Operative Dentistry 2012;37:464–73. 44. Browning WD, Chan DC, Frazier KB, Callan RS, Blalock JS. Safety and efficacy of a nightguard bleaching agent containing sodium fluoride and potassium nitrate. Quintessence International 2004;35:693–8. 45. Gerlach RW, Zhou X, McClanahan SF. Comparative response of whitening strips to a low peroxide and potassium nitrate bleaching gel. American Journal of Dentistry 2002;15:19A–23A. 46. Jorgensen MG, Carroll WB. Incidence of tooth sensitivity after home whitening treatment. Journal of the American Dental Association 2002;133:1076–82. quiz 1094–95. 47. Ontiveros JC, Eldiwany MS, Paravina R. Clinical effectiveness and sensitivity with overnight use of 22% carbamide peroxide gel. Journal of Dentistry 2012;40:e17–24. 48. Mehta D, Venkata S, Naganath M, LingaReddy U, Ishihata H, Finger WJ. Clinical trial of tooth desensitization prior to inoffice bleaching. European Journal of Oral Sciences 2013;121:477–81. 49. Ziebolz D, Hannig C, Attin T. Influence of a desensitizing agent on efficacy of a paint-on bleaching agent. American Journal of Dentistry 2008;21:77–82. 50. Tam L. Effect of potassium nitrate and fluoride on carbamide peroxide bleaching. Quintessence International 2001;32:766–70. 51. Kose C, Reis A, Baratieri LN, Loguercio AD. Clinical effects of at-home bleaching along with desensitizing agent application. American Journal of Dentistry 2011;24:379–82. 52. Armeˆnio RV, Fitarelli F, Armeˆnio MF, Demarco FF, Reis A, Loguercio AD. The effect of fluoride gel use on bleaching sensitivity: a double-blind randomized controlled clinical trial. Journal of the American Dental Association 2008;139:592–7. quiz 626–7. 53. Browning WD, Chan DC, Myers ML, Brackett WW, Brackett MG, Pashley DH. Comparison of traditional and low sensitivity whiteners. Operative Dentistry 2008;33:379–85. 54. Gallo JR, Burgess JO, Ripps AH, Bell MJ, Mercante DE, Davidson JM. Evaluation of 30% carbamide peroxide at-home bleaching

55.

56.

57.

58. 59. 60.

61.

62. 63. 64. 65.

66.

67.

68.

11

gels with and without potassium nitrate – a pilot study. Quintessence International 2009;40:e1–6. Leonard Jr RH, Smith LR, Garland GE, Caplan DJ. Desensitizing agent efficacy during whitening in an at-risk population. Journal of Esthetic and Restorative Dentistry 2004;16:49–55. discussion 56. Maghaireh GA, Alzraikat H, Guidoum A. Assessment of the effect of casein phosphopeptide-amorphous calcium phosphate on postoperative sensitivity associated with inoffice vital tooth whitening. Operative Dentistry 2014;39: 239–47. Soares DG, Basso FG, Pontes EC, Garcia Lda F, Hebling J, de Souza Costa CA. Effective tooth-bleaching protocols capable of reducing H2O2 diffusion through enamel and dentine. Journal of Dentistry 2014;42:351–8. Kim S. Neurovascular interactions in the dental pulp in health and inflammation. Journal of Endodontics 1990;16:48–53. Mantzourani M, Sharma D. Dentine sensitivity: past, present and future. Journal of Dentistry 2013;41:S3–17. Caviedes-Bucheli J, Ariza-Garcı´a G, Restrepo-Me´ndez S, Rı´os-Osorio N, Lombana N, Mun˜oz HR. The effect of tooth bleaching on substance P expression in human dental pulp. Journal of Endodontics 2008;34:1462–5. Bowles WH, Thompson LR. Vital bleaching: the effects of heat and hydrogen peroxide on pulpal enzymes. Journal of Endodontics 1986;12:108–12. Hodosh M. A superior desensitizer – potassium nitrate. Journal of the American Dental Association 1974;88:831–2. Bartold PM. Dentinal hypersensitivity: a review. Australian Dental Journal 2006;51:212–8. quiz 276. Fugaro JO, Nordahl I, Fugaro OJ, Matis BA, Mjo¨r IA. Pulp reaction to vital bleaching. Operative Dentistry 2004;29:363–8. Tal M, Oron M, Gedalia I, Ehrlich J. X-ray diffraction and scanning electron microscope investigations of fluoridetreated dentine in man. Archives of Oral Biology 1976;21: 285–90. Featherstone JD, Cutress TW, Rodgers BE, Dennison PJ. Remineralization of artificial caries-like lesions in vivo by a self-administered mouthrinse or paste. Caries Research 1982;16:235–42. Oltu U, Gu¨rgan S. Effects of three concentrations of carbamide peroxide on the structure of enamel. Journal of Oral Rehabilitation 2000;27:332–40. Friedman S. Internal bleaching: long-term outcomes and complications. Journal of the American Dental Association 1997;128:51S–5S.

601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626 627 628 629 630 631 632 633 634 635 636 637 638 639 640 641 642 643 644 645 646 647

Please cite this article in press as: Wang Y, et al. Evaluation of the efficacy of potassium nitrate and sodium fluoride as desensitizing agents during tooth bleaching treatment—A systematic review and meta-analysis. Journal of Dentistry (2015), http://dx.doi.org/10.1016/ j.jdent.2015.03.015