In-ofﬁce treatment for dentin hypersensitivity: a systematic · 2013-11-04 · for dentin hypersensitivity: a systematic review and network meta-analysis. J Clin Periodontol 2013;

In-office treatment for dentinhypersensitivity: a systematicreview and networkmeta-analysisLin P-Y, Cheng Y-W, Chu C-Y, Chien K-L, Lin C-P, Tu Y-K. In-office treatmentfor dentin hypersensitivity: a systematic review and network meta-analysis. J ClinPeriodontol 2013; 40: 53–64. doi: 10.1111/jcpe.12011.

AbstractAim: Dentin hypersensitivity, caused by the exposure and patency of dentinaltubules, can affect patients’ quality of life. The aim of this study was to undertakea systematic review and a network meta-analysis, comparing the effectivenessin resolving dentin hypersensitivity among different in-office desensitizingtreatments.Materials and Methods: A literature search was performed with electronic data-bases and by hand until December 2011. The included trials were divided into sixtreatment groups as placebo, physical occlusion, chemical occlusion, nerve desen-sitization, laser therapy and combined treatments. The treatment effects betweengroups were estimated with standardized mean differences by using a Bayesiannetwork meta-analysis.Results: Forty studies were included. The standardized mean difference betweenplacebo and physical occlusion was �2.57 [95% credible interval (CI): �4.24 to�0.94]; placebo versus chemical occlusion was �2.33 (95% CI: �3.65 to �1.04);placebo versus nerve desensitization was �1.72 (95% CI: �4.00 to 0.52); placeboversus laser therapy was �2.81 (95% CI: �4.41 to �1.24); placebo versus com-bined treatment was �3.47 (95% CI: �5.99 to �0.96). The comparisons of thefive active treatments showed no significant differences.Conclusions: The results from network meta-analysis showed that most activetreatment options had significantly better treatment outcome than placebo.

Po-Yen Lin1,3, Ya-Wen Cheng1,Chia-Yi Chu1,3, Kuo-Liong Chien2,

Chun-Pin Lin1 and Yu-Kang Tu2

1Department of Dentistry, School of Dentistry,

National Taiwan University and National

Taiwan University Hospital, Taipei, Taiwan;2Institute of Epidemiology and Preventive

Medicine, College of Public Health, National

Taiwan University, Taipei, Taiwan;3Department of Dentistry, Shin Kong Wu

Ho-Su Memorial Hospital, Taipei, Taiwan

Key words: dentin hypersensitivity; in-office

treatment; network meta-analysis;

randomized controlled trials; systematic

review

Accepted for publication 21 August 2012

Dentin hypersensitivity (DH) isdefined as “short, sharp pain arisingfrom exposed dentin in response to

stimuli typically thermal, evapora-tive, tactile, osmotic or chemical andwhich cannot be ascribed to anyother form of dental defect orpathology” (Holland et al. 1997).Clinical surveys showed the preva-lence of DH ranged from 2.8% to74%, depending on the populationstudied, study setting and studydesign (Orchardson & Collins 1987,Liu et al. 1998, Taani & Awartani2002, Rees et al. 2003, Rees & Addy

2004, Shen et al. 2009, Que et al.2010). It mostly affects individuals attheir fourth and fifth decade of life(Liu et al. 1998, Rees et al. 2003,Que et al. 2010), causing patient dis-comforts during eating or evenbreathing. The mechanism of dentinhypersensitivity had not been fullyelucidated. The most acceptedhypothesis is the hydrodynamic the-ory proposed by Brannstrom (1963).According to this theory, most pain-

Conflict of interest and source of

funding statement

No external funding, apart from thesupport of the authors’ institution,was available for this study. Theauthors declare that there are noconflicts of interest in this study.

© 2012 John Wiley & Sons A/S 53

J Clin Periodontol 2013; 40: 53–64 doi: 10.1111/jcpe.12011

inducing stimuli increase centrifugalfluid flow within the dentinaltubules, giving rise to a pressurechange throughout the entire dentin.Based on this mechanism, twophases must coincide to produceDH, the exposure of dentin and theopening of the dentinal tubular sys-tem. Therefore, the ideal treatmentof DH should be able to reduce fluidflow in dentinal tubules or block pul-pal nerve response or both (Hollandet al. 1997, Canadian AdvisoryBoard on Dentin Hypersensitivity2003).

A large number of desensitizingmethods such as dentifrices contain-ing potassium salts and in-office top-ical desensitizing agents have beenoffered to the market to solve theproblem. It has been suggested thatthe treatment of DH is to begin withan at-home method, such as a desen-sitizing dentifrice (Sowinski et al.2001, Poulsen et al. 2006, Orsiniet al. 2010); this alone may alleviatethe condition. If at-home methodsdo not satisfactorily resolve theproblem, an in-office treatment maybe indicated. When DH is localizedto one or two teeth, an in-officemethod may be the first choice oftreatment (Orchardson & Gillam2006). There is a wide range ofin-office treatments for DH, includ-ing dentin adhesives (Ide et al. 1998,Schwarz et al. 2002, Kakabouraet al. 2005, Tengrungsun & Sangkla2008), resin emulsions (Prati et al.2001, Erdemir et al. 2010), copalvarnishes (Olusile et al. 2008), glu-taraldehyde-based adhesives (Duran& Sengun 2004, Kakaboura et al.2005, Polderman & Frencken 2007,Ishihata et al. 2012), oxalates(Gillam et al. 2004, Merika et al.2006, Assis et al. 2011), fluorides(Tarbet et al. 1979, McBride et al.1991, Merika et al. 2006, Ritteret al. 2006, Fiocchi et al. 2007),potassium nitrates (Frechoso et al.2003, Sicilia et al. 2009) and lasertherapies (Gerschman et al. 1994,Lier et al. 2002, Schwarz et al. 2002,Tengrungsun & Sangkla 2008), so itcan be a challenge for selecting themost appropriate treatment forpatients, and the relative effective-ness of those treatments remainsuncertain. Traditional meta-analysisundertakes pair-wise comparisonsbetween treatments, but when thenumber of available treatments is

large, pair-wise comparisons may beinefficient or not feasible (Tu et al.2010, 2012, Hoaglin et al. 2011,Jansen et al. 2011). Network meta-analysis is a methodology for thestatistical synthesis of direct andindirect comparisons of differenttreatments and had been used indental research (Tu et al. 2010,2012). The aim of this study wastherefore to undertake a systematicreview and a network meta-analysis,comparing the effectiveness inresolving dentin hypersensitivityamong different in-office desensitiz-ing treatments.

Material and Methods

Literature search

The literature search within MED-LINE (via PubMed), ScienceDirect,ISI web of science, Ovid and Coch-rane Central Register of ControlledTrials (CENTRAL) databases up toDecember 2011 was undertaken. Toidentify relevant studies, we used thefollowing term “(dentin* OR toothOR teeth) AND (hypersensit* ORdesensiti* OR desensitize*) NOT(toothpaste OR dentifrice)”, limitedto “clinical trials” and “humans”; nolanguage restrictions were imposed.The reference lists of previously pub-lished reviews (Canadian AdvisoryBoard on Dentin Hypersensitivity2003, Orchardson & Gillam 2006,West 2008, Al-Sabbagh et al. 2009,Porto et al. 2009, Cunha-Cruz et al.2011, He et al. 2011, Sgolastra et al.2011) were crosschecked. The litera-ture search and data extractions(Fig. 1) were undertaken in dupli-cate, and quality assessment ofincluded studies, such as randomiza-tion, allocation concealment, blind-ing, intention to treat and samplesize calculation, was carried outindependently by three authors (PYLin, YW Cheng, CY Chu). Dis-agreements on study inclusions andquality assessment were resolved bydiscussions among the three authors.

Tactile, cold and evaporative airstimuli were commonly used inoutcome assessment for DH. In thissystematic review, we chose articleswhich used evaporative air test forfurther meta-analysis to minimizethe heterogeneity of methods used toassess DH. Air test is a more accu-rate method for evaluating DH

because it involves a wider area ofdentin, and it was used most oftenthan tactile test or cold stimuli testin clinical trials on DH. Moreover,air test was usually recorded byresponse-based methods, which canbe used to calculate mean differencesfor our meta-analysis. Trials usingtactile test or cold stimuli test onlywould therefore be excluded in thisreview.

Treatment group classification

Treatments used by the included tri-als were divided into six groupsaccording to the underlying mecha-nisms proposed by a recent review(Porto et al. 2009): group I: placebo;group II: physical occlusion of den-tinal tubules; group III: chemicalocclusion of dentinal tubules; groupIV: nerve desensitization; group V:photobiomodulating action (Lasertherapy); and group VI: combinedtreatment (any combination ofgroups II–V) (Table 1).

Data extraction and statistical analysis

Three authors (PY Lin, YW Cheng,CY Chu) performed data extraction.Most of the literatures used visualanalogue scales (VAS) or verbal rat-ing scales (VRS) for pain assessmentof DH (Holland et al. 1997). Thenumber of participants, means andstandard deviations of treatmenteffects were extracted from thereports or using a pooled estimationformula which assumed a correlationcoefficient of baseline and outcomemeasurement equal to 0.5 (Tu et al.2005). When multiple teeth weretreated within one patient, the stan-dard error of means for treatmenteffects were derived from the stan-dard deviation by using the numberof patients as the unit of analysis. Ifthe number of patients in each groupwas not available, we contacted thecorresponding authors by email forrequesting more detailed informa-tion, or assumed that the numbersof participants were equal for alltreatment groups.

Both VAS and VRS were usedfor evaluating treatment effects ofDH products in clinical trials, butthe scales of them differed. VASconsists of a straight line that is10 cm in length, the ends of whichare defined with the words: “no

© 2012 John Wiley & Sons A/S

54 Lin et al.

pain” and “severe pain” (Scott &Huskisson 1976). The scale of VASis usually 0–10 or 0–100. VRS usesword descriptors as a scaling tech-nique to describe variations of pain.The scale is usually 0–3 as follows:0, no discomfort; 1, discomfort ormild pain; 2, severe pain duringstimulation; 3, severe pain whichpersisted for some time after stimula-tion (Holland et al. 1997). If thestudy had more than one follow-upperiod, we would use the final assess-ment for data extraction.

To combine data from differentscales, it has been suggested thatdividing the mean difference in eachstudy by that study’s standard devia-tion to create a standardized meandifference which would be compara-ble across studies (Glass 1976). Thestandardized mean difference can beviewed as the mean difference that

would have been obtained if all datawere transformed into a scale wherethe standard deviation within-groupwas equal to 1.0.

Twelve articles were excluded(Kielbassa et al. 1997, Prati et al.2001, Marsilio et al. 2003, Singalet al. 2005, Merika et al. 2006, Ritteret al. 2006, Fiocchi et al. 2007, Azar-pazhooh et al. 2009, Dilsiz et al. 2009,Banerjee et al. 2010, Jalali & Lindh2010, Sethna et al. 2011) because theytested the treatments classified as thesame group. For example, Dilsiz et al.(2009) compared two types of lasers,the Nd:YAG laser and the 685-nmdiode laser, for treating DH.

Network meta-analysis, for multi-ple treatments comparisons by incor-porating direct and indirect evidence,was undertaken using the Bayesianhierarchical random-effects model-ling. Because the included studies

reported treatment outcomes with dif-ferent lengths of follow-ups, the lengthof follow-up was stratified into twocategories using 1 month as the cut-offvalue. The study design was dividedinto parallel group and split-mouthdesign to account for the heterogene-ity in treatment effects. The authorsassumed a within-patient correlationcoefficient equal to 0.25 for split-mouth trials. Standard pair-wisemeta-analyses of direct comparisonsamong each group were carried outand compared to results from thenetwork meta-analysis. Meta-regres-sions with covariates such as studydesign, length of follow-ups, multipletreatment courses and interactionterms among them were also con-ducted to explore if they could explainthe heterogeneity.

In addition, the number of timesthe same desensitizing treatment

Fig. 1. Flowchart for literature search and identifications of articles for review.

Table 1. Grouping of the included articles for network meta-analysis

Group Group IPlacebo

Group IIPhysical occlusion of

dentinal tubules

Group IIIChemical occlusion of

dentinal tubules

Group IVNerve

desensitization

Group VPhotobiomodulating

action

Group VICombinedtreatment

Treatmentoption

No treatmentWaterNot specifiedplaceboDesensitizingtoothpaste

Pumice pasteSodium bicarbonateHydroxyapatitesBioglassesGlass ionomersDentin bonding agentsResins

FluoridesOxalatesGlutaraldehyde-basedagentsCalcium compounds

Potassium nitratesGuanethidine

Laser therapy Any combinationof Groups II–V


DH network meta-analysis 55

Table

2.

Summary

ofstudiesincluded

inthenetwork

meta-analysis

Study,year,country

Group

Treatm

entagent

Subject

number

Treatm

ent

effect

SD

Pain

score

type

Study

design

Follow-up

period

Treatm

ent

courses

OHI

Tarbet

etal.(1979),NY

INotreatm

ent

20patients

�0.11

1.08

VRS(0–3)

Parallel

14days

1No

III

NaF

20patients

�0.01

1.43

McB

rideet

al.(1991),UK

IDeionized

water

48patients

�0.31

0.83

VRS(0–4)

Parallel

Immediate

1N/A

III

Iontophoresiswith

2%

NaF

47patients

�2.11

0.61

Dondidall’O

rologio

&Malferrari(1993),Italy

INotreatm

ent

34teeth

�2.16

0.60

VRS(0–3)

Splitmouth

6months

1N/A

III

GlumathreePrimer

40teeth

�2.26

0.53

III

Gluma2000Conditioner

42teeth

�0.29

0.42

Dunne&

Hannington-K

iff

(1993),UK

IDistilwater

20patients

�1.20

2.10

VAS(0–10)

Parallel

Immediate

1N/A

IVGuanethidine

19patients

�3.80

2.60

Gerschmanet

al.(1994),

Denmark

INotreatm

ent

28patients

�0.80

1.65

VAS(0.100)

Parallel

8weeks

4Yes

VGaAlA

slaser

21patients

�3.90

1.85

Ideet

al.(1998),UK

INotreatm

ent

16patients

�8.10

27.91

VAS(0.100)

Splitmouth

1week

1No

IIDentinbondingagent

16patients

�25.30

27.89

Yateset

al.(1998),UK

IWater

36patients

�3.88

1.99

VAS(0–10)

Splitmouth

84days

3N/A

III

Amorphouscalcium

phosphate

36patients

�3.91

1.73

Morriset

al.(1999),USA

IDistilwater

16teeth

�32.00

19.30

VAS(0–100)

Splitmouth

3months

1N/A

III

Oxalate-containingresin

solution

16teeth

�33.40

21.90

III

0.7%

fluoridesolution

18teeth

�36.20

28.80

Lieret

al.(2002),Norw

ay

IPlacebo

17patients

�2.99

2.33

VAS(0–10)

Splitmouth

16weeks

1No

VNd:Y

AG

laser

17patients

�2.72

2.15

Schwarz

etal.(2002),

Germany

INotreatm

ent

30patients

0.20

0.36

VRS(1–4)

Splitmouth

6months

1Yes

IIResin

adhesives

30patients

�0.30

0.40

VEr:YAG

laser

30patients

�1.90

0.44

Coronaet

al.(2003),Brazil

III

Fluoridevarnish

12patients

�1.17

0.80

VRS(0–3)

Splitmouth

30days

5N/A

VGaAlA

slaser

12patients

�1.37

0.70

Frechoso

etal.(2003),

Spain

IPlacebo

15patients

�1.46

0.74

VRS(0–3)

Parallel

14days

1Yes

IV5%

NK

15patients

�1.40

0.98

IV10%

NK

15patients

�1.66

1.11

Zhang(2003),China

IIDentinbonding(occlusal)

10patients

�1.67

0.74

VRS(0–3)

Splitmouth

3months

1N/A

IIEnamel

bonding(occlusal)

11patients

�1.00

0.80

IIDentinbonding(cervical)

11patients

�1.75

0.74

IIEnamel

bonding(cervical)

9patients

�1.08

0.83

IIDentinbonding(root)

8patients

�1.25

0.74

IIEnamel

bonding(root)

12patients

�0.58

0.83

III

75%

ofNaFglycerine

paste(occlusal)

10patients

�1.00

0.96

III

75%

ofNaFglycerine

paste(cervical)

12patients

�0.92

0.83

III

75%

ofNaFglycerine

paste(root)

10patients

�0.67

0.82


56 Lin et al.

Table

2.(Continued)

Study,year,country

Group

Treatm

entagent

Subject

number

Treatm

ent

effect

SD

Pain

score

type

Study

design

Follow-up

period

Treatm

ent

courses

OHI

Duran&

Sengun(2004),

Turkey


44teeth

�1.71

2.61

VAS(0–10)

Splitmouth

3months

1N/A

III

HEMA

+NaF

59teeth

�1.97

2.05

VI

Dentinbondingagent+

FluorideLiner

76teeth

�3.12

2.21

III

Glutaraldehyde-basedagent

42teeth

�1.38

4.96

III

Sodium

&calcium

fluoride

56teeth

�1.29

1.37

Gentile

&Greghi(2004),

Brazil

ICuringlight

16patients

�4.42

2.68

VAS(0–10)

Parallel

6weeks

6Yes

VGaAlaslaser

16patients

�3.91

2.69

Gillam

etal.(2004),UK

IPlacebo

13patients

�0.72

0.75

VAS(0–10)

Splitmouth

4weeks

1N/A

III

Ferricoxalate

13patients

�0.30

0.72

Kakaboura

etal.(2005),

Greece

IWater

40teeth

�0.24

0.14

VRS(0–3)

Splitmouth

9months

1Yes


40teeth

�0.63

0.15

III

Glutaraldehyde-based

agent

40teeth

�0.99

0.14

Pamiret

al.(2005),Turkey

IDesensitizer-free

bio-adhesivegel

16teeth

�0.50

0.36

VAS(0–10)

Splitmouth

8weeks

1No

IIPromptL-pop

28teeth

�3.10

0.30

III

2%

NaFbio-adhesive

gel

30teeth

�3.30

0.30

IV5%

Potassium

nitrate

bio-adhesivegel

32teeth

�4.20

0.27

Zantner

etal.(2006),

Germany

IPlacebo

72patients

�27.40

26.50

VAS(0–100)

Splitmouth

1week

1N/A

III

Potassium

fluoridevarnish

72patients

�26.90

24.90

Polderman&

Frencken

(2007),theNetherlands

IIGlass

ionomer

14patients

�2.78

0.91

VRS(0–3)

Splitmouth

3months

1N/A

III


14patients

�1.36

1.26

Tengrungsun&

Sangkla

(2008),Thailand


70patients

�1.85

0.46

VRS(0–3)

Splitmouth

30days

1N/A

VGaAlA

slaser

70patients

�0.71

0.76

Hamlinet

al.(2009),USA

IIPumicepaste

23patients

�0.35

0.51

VRS(0–3)

Parallel

Immediate

1N/A

III

8%

arginineandcalcium

carbonate

22patients

�1.19

0.51

Ipci

etal.(2009),Turkey

III

2%

NaF

10patients

�0.75

0.59

VRS(1–4)

Parallel

6months

1Yes

VI

2%

NaF

+CO2laser

10patients

�1.94

0.47

VI

2%

NaF

+Er:YAG

laser

10patients

�1.87

0.64

VCO2laser

10patients

�1.99

0.55

VEr:YAG

laser

10patients

�1.98

0.50

Kara

&Orbak(2009),

Turkey

III

Fluoridevarnish

10patients

�5.05

0.90

VAS(0–10)

Parallel

4weeks

1Yes

VNd:Y

AG

laser

10patients

�4.62

0.92

Ozenet

al.(2009),Turkey

IWater

13patients

�1.62

8.40

VAS(0–100)

Parallel

7days

1Yes

III

Glutaraldehyde-based

agent

13patients

�48.10

6.14

III

Fluoridevarnish

13patients

�51.50

8.85

IVNK

gel

13patients

�57.40

6.07

Schiffet

al.(2009),USA

IIPumicepaste

36patients

�2.70

0.34

VRS(0–3)

Parallel

12weeks

1Yes

III

8%

arginineandcalcium

carbonate

32patients

�2.73

0.34

Sicilia

etal.(2009),Spain

IPlacebo

15patients

�0.67

0.82

VRS(0–3)

Parallel

60days

1Yes

IV10%

NK

15patients

�0.73

1.10

VDiodelaser

15patients

�1.53

0.74



Table

2.(Continued)

Study,year,country

Group

Treatm

entagent

Subject

number

Treatm

ent

effect

SD

Pain

score

type

Study

design

Follow-up

period

Treatm

ent

courses

OHI

Vieiraet

al.(2009),Brazil

IPlacebo

8patients

�3.84

2.72

VAS(0–10)

Parallel

3months

4N/A

III

3%

potassium

oxalate

8patients

�3.88

2.78

VGaAlA

slaser

8patients

�4.09

2.59

Dilsizet

al.(2010b),Turkey

IDesensitizingtoothpaste

26teeth

�3.89

1.01

VAS(0–10)

Splitmouth

60days

1Yes

VDesensitizingtoothpaste+

diodelaser

26teeth

�6.00

0.68

Dilsizet

al.(2010a),Turkey

INotreatm

ent

24teeth

�0.25

1.12

VAS(0–10)

Parallel

60days

3N/A

VEr:YAG

laser

24teeth

�5.37

1.51

VNd:Y

AG

laser

24teeth

�7.25

0.97

VDiodelaser

24teeth

�4.04

0.91

Eitner

etal.(2010),

Germany

INotreatm

ent

21patients

�1.60

1.31

VAS(0–10)

Parallel

1month

1Yes

III

Gluma

20patients

�2.86

1.90

III

Fluoride

21patients

�2.27

1.79

Erdem

iret

al.(2010),

Turkey

IIResin

emulsion

44patients

�2.16

2.31

VAS(0–10)

Splitmouth

4weeks

1N/A

VI

Oxalicacid+dentinbonding

agent

43patients

�3.37

2.77

III

Fluoridecontaining

adhesives

44patient

�4.34

2.65

Shetty

etal.(2010),India

IWater

45patients

�23.79

0.51

VAS(0–10)+

VRS(0–3)

Splitmouth

8weeks

1–5

Yes

INotreatm

ent

45patients

�24.12

0.68

IIDuraphat+

Hydroxyapatite-dry

powder

45patients

�23.12

0.57

IIDuraphat+

Hydroxyapatite

precipitate

45patients

�24.12

0.54

Aranha&

DePaula

Eduardo(2012),Brazil

INotreatm

ent

7patients

�2.46

2.36

VAS(0–10)

Parallel

1month

1Yes

VEr:YAG

laser

7patients

�3.16

2.30

V0.25W

Er,Cr:YSGG

laser

7patients

�2.26

0.85

V0.5W

Er,Cr:YSGG

laser

7patients

�1.67

1.27

Assiset

al.(2011),Brazil

IPlacebo

13patients

�0.70

1.00

VRS(0–3)

Splitmouth

4weeks

4N/A

III

3%

potassium

oxalate

13patients

�0.80

1.00

III

Calcium

andfluoride

compounds

13patients

�0.70

1.00

Castillo

etal.(2011),

Lim

a,Peru

IWater

34patients

0.40

16.20

VAS(0–100)

Parallel

7days

1N/A

III

Diamminesilver

fluoride

37patients

�35.80

27.70

Castillo

etal.(2011),

Cusco,Peru

IWater

29patients

�5.50

18.10

VAS(0–100)

Parallel

7days

1N/A

III

Diamminesilver

fluoride

26patients

�23.40

21.00

Orhanet

al.(2011),Turkey

INotreatm

ent

4patients

�2.25

11.99

VAS(0–100)

Parallel

7days

6(laser)

Yes

IWater

4patients

�0.00

4.02

III


4patients

�55.30

8.89

VGaAlA

slaser

4patients

�59.00

11.68

Yilmazet

al.(2011a),Turkey

INotreatm

ent

42patients

�0.79

1.84

VAS(0–10)

Splitmouth

3months

1Yes

VEr,Cr:YSGG

laser

42patients

�5.67

1.58

Yilmazet

al.(2011c),Turkey

INotreatm

ent

51patients

�0.50

1.40

VAS(0–10)

Splitmouth

3months

1Yes

VEr,Cr:YSGG

laser

51patients

�6.20

1.28

VGaAlA

slaser

51patients

�6.00

1.21

Yilmazet

al.(2011b),Turkey

ISaline(N

aFcontrol)

48patients

�0.06

1.13

VAS(0–10)

Splitmouth

6months

1Yes

INotreatm

ent(Lasercontrol)

48patients

�0.17

1.40

III

NaF

48patients

�3.35

1.77

VGaAlA

slaser

48patients

�5.16

1.45

SD,standard

deviation;OHI,oralhygieneinstruction;VRS,verbalratingscales;VAS,visualanaloguescales;N/A

,notavailable.


58 Lin et al.

being given to each patient in thestudy and any oral hygiene instruc-tion given to patients after treat-ments were also recorded. If thepatients were instructed to maintainthe same habits during the trial, itwas recorded as no oral hygieneinstruction being given. The oralhygiene instruction included tooth-brush types, brushing methods andfrequency, and eating habits.

The Bayesian random-effects net-work meta-analysis was performedusing the statistical software Win-BUGS (version 14.3, MRC Biostatis-tics Unit, Cambridge, UK) with50,000 simulations. Non-informativepriors were used throughout theanalysis. The standard pair-wise ran-dom-effects meta-analysis, heteroge-neity between studies and meta-regressions were performed usingstatistical software STATA (version11.2, StataCorp LP, College Station,TX, USA). The statistical signifi-cance level was set at 5%.

Results

Study selection

Figure 1 summarized the details ofthe study selection process and thereasons for exclusion. A total of 290potential relevant titles, abstractsand articles were found electroni-cally, plus reference lists of reviewsand related articles, of which 194were screened for further evaluationby retrieving full texts. Finally, weidentified 40 trials that met all inclu-sion criteria. The characteristics ofthese included trials were listed inTable 2.

Study description

The 40 trials included in the finalmeta-analysis were full reports pub-lished between 1979 and 2011, and36 of them were published after2000. Table 2 showed the summaryof grouping and intervention. Of all40 studies, 22 were split-mouth trialsand the others were parallel trials.Follow-up periods were somewhatdiverse in these studies, ranged fromimmediate (McBride et al. 1991,Dunne & Hannington-Kiff 1993,Hamlin et al. 2009) to 6–9 months(Dondi dall’Orologio & Malferrari1993, Schwarz et al. 2002, Kakabo-ura et al. 2005, Ipci et al. 2009,

Yilmaz et al. 2011b). Seven studies(Dondi dall’Orologio & Malferrari1993, Morris et al. 1999, Duran &Sengun 2004, Kakaboura et al. 2005,Pamir et al. 2005, Dilsiz et al. 2010a,b) reported their treatment effects bythe number of teeth as the unit, sowe estimated the numbers of partici-pants were equal in each group ofthese trials. Adverse events were notobserved during these studies.

Quality of studies

Appendix S1 shows the quality of theincluded trials. Thirty-seven studiesdescribed as randomized; of them, 21studies clearly described the alloca-tion process. Triple blinding (patient,caregiver and examiner blinding) wasperformed in five of the 44 trials(Frechoso et al. 2003, Zantner et al.2006, Sicilia et al. 2009, Castilloet al. 2011, Orhan et al. 2011). Themasking system used was clearlydescribed in nine trials (Dunne &Hannington-Kiff 1993, Ide et al.1998, Ozen et al. 2009, Sicilia et al.2009, Castillo et al. 2011, Orhanet al. 2011, Yilmaz et al. 2011a, b, c),and the remaining were unclearabout it. Seven of the included trialsreported sample size and statisticalpower calculations (Morris et al.1999, Zantner et al. 2006, Siciliaet al. 2009, Castillo et al. 2011, Yil-maz et al. 2011a, b, c).

Network meta-analysis

Forty studies were grouped into sixdifferent kinds of treatments in thenetwork meta-analysis, yielding 15possible pairs of comparisons(Fig. 2). Evidence of direct compari-sons was only available in 9 of 15pairs (Figs 2 and 3).

The overall results from networkmeta-analysis showed that most activetreatment options including physicalocclusion group, chemical occlusiongroup, laser therapy group and com-bined treatment group had signifi-cantly better treatment outcome thanplacebo group except nerve desensiti-zation group (Appendix S2). The stan-dardized mean difference betweenplacebo group versus physical occlu-sion group was �2.57 [95% credibleinterval (CI): �4.24, �0.94]; placebogroup versus chemical occlusion groupwas �2.33 (95% CI: �3.65, �1.04);placebo group versus nerve desensiti-zation group was �1.72 (95% CI:�4.00, 0.52); placebo group versuslaser therapy group was �2.81 (95%CI: �4.41, �1.24); placebo group ver-sus combined treatment group was�3.47 (95% CI: �5.99, �0.96). How-ever, comparisons of the five activetreatment groups showed no signifi-cant differences. The combined treat-ment group had better outcomes thanthe other groups (�0.90 comparedwith physical occlusion group, �1.14compared with chemical occlusiongroup, �1.75 compared with nervedesensitization group, �0.65 com-pared with laser therapy group)although the differences were not sig-nificant either. The study designsincluding split-mouth-designed trialsversus parallel-designed trials, follow-up periods, and multiple treatmentcourses versus single treatmentshowed no significant differences.

Pair-wise meta-analysis, heterogeneity

and meta-regression

Results from standard pair-wisemeta-analysis of overall studiesshowed that physical occlusiongroup, chemical occlusion group,

Figure 2. Network for the comparisons among different in-office treatments for dentinhypersensitivity. Dotted lines refer to those comparisons that have not been testeddirectly in clinical trials. The width of the solid lines is in proportion to the amount ofevidence available in the literatures.



Fig. 3. Forest plot of the standard pair-wise meta-analysis for different in-office treatments for dentin hypersensitivity.


60 Lin et al.

laser therapy group and combinedtreatment group had significantlybetter treatment outcomes than pla-cebo group (Appendix S2 andFig. 3), which was similar to theresult of network meta-analysis. Thecomparisons of active treatmentgroups showed that laser therapygroup had significant better treat-ment outcome than physical occlu-sion group; however, only one studyprovided the data (Tengrungsun &Sangkla 2008). It also showed thatcombined treatment group had sig-nificant better outcome than physicalocclusion group and chemical occlu-sion group, with three trials providingthe data (Duran & Sengun 2004, Ipciet al. 2009, Erdemir et al. 2010). Thestatistical heterogeneity of thesecomparisons was high (I-squared= 88.6% ~96.7%, Fig. 3) except thecomparison between physical occlu-sion group and combined treatmentgroup (I-squared = 0.0%, p = 0.71).Meta-regressions with covariatesincluding the length of follow-ups,study design, multiple treatmentcourses and interaction terms amongthem were tested and none of theresults was significant (p > 0.05).

Discussion

The current systematic review attem-pted to analyse all published clinicaltrials to assess evidence for differentin-office desensitizing agents of DHtreatments. After review and critiques,40 studies were included into the finalanalysis (Fig. 1). With networkmeta-analysis, the result could provideclinical researchers some usefulinformation.

The results from network meta-analysis and standard pair-wise meta-analysis were in general consistent:physical occlusion group, chemicalocclusion group, laser therapy groupand combined treatment group hadsignificantly better treatment out-comes than placebo group (AppendixS2). Among the comparisons of activetreatments, the pair-wise meta-analy-sis showed that laser therapy groupachieved better treatment outcomethan physical occlusion group whilethe network meta-analysis showedlittle differences. Although fivestudies directly compared placeboand physical occlusion group and 13directly compared placebo and lasertherapy group, only one study

directly compared physical occlusionand laser (Tengrungsun & Sangkla2008) (Fig. 3). In Tengrungsun’sstudy, they directly compared theclinical efficacy of the 30-mW Ga-AlAs laser for 1 min and dentinbonding agent in treating DH andconcluded that the GaAlAs laser hadless desensitizing efficacy then thedentin bonding agent. The networkmeta-analysis incorporated bothdirect and indirect evidence withinthe whole network and also includedall different types of lasers as onegroup. The inconsistency in resultsbetween direct and indirect evidencemay be due to chance alone, as onlyone study provided direct evidence,but it may also indicate the treatmenteffects of different types of lasers arenot the same.

In this study, the network meta-analysis showed that regarding thetreatment efficacy of dentin hyper-sensitivity, in-office products wasmore effective than the placebo,which indicated that the activein-office agent could overcome the“placebo effect” and demonstratedtheir efficacy. Although the currentstudy did not show any preferencefor the five groups of active agentsincluded, both network and stan-dard meta-analyses indicated thatthese active treatments achieved bet-ter outcomes to relieve patients’ DHsymptoms than the placebo group(Appendix S2 and Fig. 3), demon-strating that the treatments weremore helpful than placebo effect orthe Hawthorne effect. So far, therewas not enough evidence to showthat toothpastes containing potas-sium is effective in relieving symp-toms of DH (Poulsen et al. 2006),but after considering patient’s cost-effectiveness, Orchardson & Gillam(2006) and the Canadian AdvisoryBoard on Dentin Hypersensitivity(Canadian Advisory Board on Den-tin Hypersensitivity 2003) suggestedthe treatment protocol of DH is tobegin with home-care method, suchas a desensitizing dentifrice. If thesymptom persists, an in-officetreatment is then indicated. Thisstrategy was much more conserva-tive and logical.

Grossman suggested that theideal desensitizing agent should notirritate or endanger the integrity ofthe pulp, should be relatively pain-less on application or shortly after-

wards, should be easily applied,rapid in action, permanently effec-tive and finally should not discol-our tooth structure (Grossman1935). Unfortunately, no such treat-ment has been identified to date.However, in the current study, wefound that none of the includedtrials reported any adverse effectsor pulp damages during the studyperiods, so these in-office treatmentoptions are relatively safe and metthe first criteria of the ideal desen-sitizing agent, and some authorsstill regard laser therapies as rela-tively invasive considering theirpotential damage to pulp, though(Launay et al. 1987, Schwarz et al.2008).

Erosion is currently believed tobe the major factor involved in toothwear and subsequent dentinaltubules exposure (Dababneh et al.1999). Therefore, reducing dietaryacids intake and oral hygieneinstruction to patients with DHshould be included as part of standardmanagement of dentin hypersensitiv-ity (Canadian Advisory Board onDentin Hypersensitivity 2003).Among the included trials in the pres-ent study, only three of them men-tioned the instruction of avoidingexcessive dietary acids or providingdietary counselling (Ipci et al. 2009,Shetty et al. 2010, Aranha &De PaulaEduardo 2012). If this predisposingfactor was not removed or modified,the treatment may provide only short-term success (Canadian AdvisoryBoard on Dentin Hypersensitivity2003), which may partly contribute tolimited efficacy of currently availabledesensitizing therapies.

The objectives of the desensitizingtherapy are to alleviate the symp-toms of pain or discomfort and toimprove the life quality of thepatients with DH, while evaluatingpatients’ response to clinical stimulimay be viewed as a surrogate end-point (Holland et al. 1997). In thecurrent study, we reviewed 40 clini-cal trials using in-office desensitizingagents, and these trials usedcontrolled clinical stimuli, such asevaporative air, tactile and thermal,to evaluate the baseline and post-treatment response of the patients;only two evaluated how the efficacyof treatment affects the patients’everyday life (Frechoso et al. 2003,Sicilia et al. 2009), which should be



the most important clinical outcomebut was often neglected.

To minimize the differencesbetween the trials, we used stan-dardized mean difference and onlyincluded trials with evaporative airtest. However, the result of pair-wise meta-analysis still showed rela-tively high statistical heterogeneity,with I-squared = 88.6% ~ 96.7%(Fig. 3). We explored the heteroge-neity by undertaking meta-regres-sion with covariates such as lengthof follow-ups, study design andmultiple treatment courses, butboth network and standard meta-regressions showed no significantimpact of these covariates.

Finally, this systematic review hasseveral limitations. Firstly, mosttrials did not report how randomiza-tion was undertaken and whethertreatment allocations were unknownto caregivers, although treatmentallocations sometimes become recog-nizable owing to materials anddevices used. Secondly, due to insuf-ficient reporting of the results in theincluded studies, some assumptionssuch like the number of participantsin each group were made in the dataextraction procedure. Thirdly, the tri-als that did not use evaporative airtest to evaluate DH or the treatmentscategorized within the same groupwere excluded, and this might losesome important information. Finally,although we divided the studies intosix groups in the network meta-anal-ysis, we did not conduct any test forfurther within treatment groupcomparisons.

Conclusion

In conclusion, the results from net-work meta-analysis showed thatmost active treatment optionsincluding physical occlusion, chemi-cal occlusion, laser therapy and com-bined therapy had significantlybetter treatment outcome than pla-cebo. The comparisons of the fiveactive treatment groups showed nosignificant differences.

Acknowledgements

The authors thank Renee Tseng(Medical library of Taiwan Advent-ist Hospital) for her contribution tothe literature search.

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Supporting Information

Additional Supporting Informationmay be found in the online versionof this article:

Appendix S1. Quality assessment ofthe included articles for networkmeta-analysis.Appendix S2. Results of networkand standard meta-analysis.

Address:Yu-Kang TuInstitute of Epidemiology and PreventiveMedicineCollege of Public Health, National TaiwanUniversityRoom 539, 17 Xu-Zhou RoadTaipeiTaiwanE-mail: [email protected]

Clinical Relevance

Scientific rationale for the study: Alarge number of in-office desensitiz-ing agents are available for treatingdentin hypersensitivity (DH), andthis study used the network meta-analysis to compare the relative

effectiveness among those agents inresolving DH.Principal findings: Most active agentsachieved better treatment outcomethan placebo group, but there wasno substantial difference betweenactive agents.

Practical implications: Althoughcurrently there is no gold-standardtreatment for DH, commonly usedin-office desensitizing agents forDH seemed to be effective.


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Documents

In-ofﬁce treatment for dentin hypersensitivity: a systematic · 2013-11-04 · for dentin hypersensitivity: a systematic review and network meta-analysis. J Clin Periodontol 2013;