REVIEW

Updates in oral appliance therapy for snoringand obstructive sleep apnea

Hui Chen & Alan A. Lowe

Received: 27 January 2012 /Revised: 27 January 2012 /Accepted: 16 April 2012# Springer-Verlag 2012

AbstractBackground Obstructive sleep apnea (OSA) is increasinglybeing recognized by the public due to its life-threateningand low curability rate nature. Oral appliances (OAs) wereintroduced as a treatment option for both non-apneic snoringand OSA to maintain the patency of the upper airway duringsleep by repositioning the mandible, tongue, and soft palate.Results Over the past decade, OAs are enthusiastically stud-ied and concluded as a simple, silent, bed partner-friendly,less invasive, tolerable, and efficacious choice for mild-to-moderate OSA. In the meantime, some challenges remainuncertain such as titration management, 3D image diagnos-tic tools reliability, and long-term adherence for adultpatients. Improvement of temporomandibular joint (TMJ)monitoring and management is recommended, althoughthere is no scientific evidence suggesting consistent unde-sirable long-term effects of OA on the TMJ. Now thatpediatric OSA is being diagnosed more frequently, OAtherapy is becoming a promising option for children as well.Conclusion Consistent follow-up and management areneeded to increase clinical success rates in OA therapy forOSA. Further educational preparation and support is re-quired for dental and medical professionals to recognizeOSA and ensure the best possible patient care.

Keywords Obstructivesleepapnea .Oralappliance therapy .

Mandibular advancement . Snoring . Titration . Side effects .

Compliance . Adherence . Efficacy

Introduction

Obstructive sleep apnea (OSA) is characterized by repeti-tive episodes of upper airway obstruction that occur duringsleep, usually associated with a reduction in blood oxygensaturation, loud snoring, witnessed breathing interruptions,and/or arousal due to gasping or choking in the presence ofobstructive respiratory events [1]. OSA is associated withsignificant co-morbidities such as cardiovascular, metabol-ic/neurocognitive complications, motor vehicle crashes,and occupational accidents. In population-based epidemi-ology studies, the prevalence of OSA is different depend-ing upon the age, gender, obesity, ethnicity, severity, andinvestigation methodology [2]. The American NationalSleep Foundation 2005 poll based on Berlin questionnairescores indicated the prevalence of OSA ranged from 16%to 37% in the 18–65+ age groups with the 50–64-year-oldgroup having the greatest chance of being diagnosed withthe disease in both gender groups (37% in males and 29%in females) [3].

Currently, the in-laboratory polysomnography (PSG) isused as a standard to diagnose OSA [4]. The severity ofOSA is differentiated based on Apnea Hypopnea Index(AHI), which is the average number of apneas and hypo-pneas per hour of sleep. Since each apnea event differs induration (some last for 10 s while others a minute long), thenumber of events may not be better than the total time of airblockage hourly in order to demonstrate the true severity ofOSA.

Behavioral modifications for OSA treatment includeweight loss, alcohol avoidance, and changes in sleepingposition. If these conservative management practices donot solve the problem, then therapeutic interventions suchas continuous positive airway pressure (CPAP), oral appli-ances (OAs), and/or a range of surgical procedures can be

H. Chen (*) :A. A. LoweDivision of Orthodontics, Department of Oral Health Sciences,Faculty of Dentistry, The University of British Columbia,2199 Wesbrook Mall,Vancouver, BC, Canada V6T 1Z3e-mail: huichen@dentistry.ubc.ca

Sleep BreathDOI 10.1007/s11325-012-0712-4

used. In a recent practice parameters article published by theAmerican Academy of Sleep Medicine (AASM), OAs areindicated for snorers, for mild to moderate OSA subjects, forsevere OSA subjects who have not responded to CPAP, whoare not appropriate candidates for CPAP, or whose previousattempts to use CPAP failed [5].

This review will summarize the current understandingand controversy of OA therapy for the treatment of OSAand/or non-apneic snoring from publications collected overthe past 10 years (2001–2011). Searches were limited toarticles in English, clinical trials, meta-analyses, practiceguidelines, randomized controlled trials, and reviews.The detailed literature search criteria are described inFig. 1. The updated studies on pediatric OSA, three-dimensional (3D) imaging analysis on upper airwaystructure, titration strategies, and side-effects manage-ment will be integrated to address further research chal-lenges in the field.

OA therapy in general

Types and action mechanisms

There are over 100 OA designs available on the marketwhich differ in the fabrication material, location of thecoupling mechanism, titration capability, degree of custom-ization, amount of vertical opening, and lateral jaw move-ment. Most of OAs cover the upper and lower teeth and holdthe mandible in an advanced position with respect to theresting position [1]. These appliances are further dividedinto titratable and non-titratable OAs based on the capabilityof the “dose-dependent” effect of mandibular protrusion.The tongue retaining devices (TRDs) and tongue stabilizingdevices (TSDs) may be an alternative for edentulouspatients or patients with inadequate healthy teeth and aredesigned to hold the tongue in a forward position withrespect to the resting position. Boil-and-bite appliancesmay be used for patients while repairs to their regular OAsare being made.

It has been agreed that the rationale for OA therapy isto advance the mandible and tongue in order to positivelyimpact upper airway caliber and function [6, 7]. Theupper airway behind the base of the tongue and the softpalate is vulnerable due to a lack of rigid skeletal support.Airway patency is determined by a balance of forces asestablished by the interplay of anatomical factors anddilator muscle activation. Dilator muscle activation isdirectly related to airway narrowing and reduces resis-tance across patients with OSA [8]. OAs may improveupper airway patency during sleep by decreasing upperairway collapsibility and improving upper airway muscletone [9].

Mechanisms supported by images

Upper airway 3D imaging is an ideal modality to exam-ine the anatomy of the pharynx and surrounding cranio-facial and soft-tissue structures. Both static and dynamicupper airway imaging techniques have been used tosignificantly verify the understanding of the pathogene-sis of OSA and the therapeutic bio-mechanisms duringwakefulness and sleep. In a MRI study on upper airwaystructure, both mandibular repositioners and TSDsaltered upper airway geometry associated with move-ment of the parapharyngeal fat pads away from theairway. TSD increased velopharyngeal lateral diameterto a greater extent and also increased antero-posteriordiameter with anterior displacement of the tongue [7].Awake videoendoscopy suggests that mandibular ad-vancement enlarges the upper airway and may reduceupper airway dilator muscle activity during inspiration[10]. With sleep videofluoroscopy, Lee and colleagues[11] found that the length of the soft palate and theangle of mouth opening increased while the retropalatalspace and retrolingual space became narrower duringsleep events. The OA had marked effects in wideningthe retropalatal and retrolingual space and decreasing thelength of the soft palate with the mouth closed. The OAappears to enlarge the pharynx to a greater degree in thelateral than in the sagittal plane at the retropalatal andretroglossal levels of the pharynx based on CT findings[12]. Recently, patient-specific modeling created from3D reconstruction of airway and related anatomy tovisualize the different obstruction sites has been usedto choose treatment alternatives [13, 14].

Inadequate knowledge of OSA in dental professionals

Dentists often refer and treat OSA with OAs sinceanatomical structures such as the tongue, soft palate,tonsil tissues, and tori are routinely checked in regulardental exams. In a retrospective analysis of 175 maleand 156 female patients who received dental care, 67%of the men and 28% of the women were identified asbeing at risk of at least mild OSA. Over 33% of themen and 6% of the women surveyed were predicted tohave moderate or severe OSA [15]. However, a survey[16] showed that 58% of dentists in a group of 192 USpractitioners could not identify common signs andsymptoms of OSA; 40% knew little or nothing aboutOA therapy for OSA while 30% learned about it duringpostgraduate training. Some 54% have never consultedwith a physician for a suspected OSA patient in theirpractice; 75% of dentists have never had patientsreferred to them by a physician. This under-preparedsituation demands that basic education and training

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regarding OSA and OAs be provided in dental schoolsand continuing education programs. In addition,

improved co-operation between dentists and physiciansis required for better overall patient care.

Fig. 1 Flow diagram of the citation selection process

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Efficacy of OA therapy

Indicators for OA candidates

OA patients must have a complete medical review by a sleepspecialist and a PSG examination if required before theinitiation of treatment. Candidates for a mandibular reposi-tioner require ample healthy teeth upon which to seat theappliance, the absence of significant temporomandibulardisorder (TMD), an adequate range of jaw motion, andsufficient manual dexterity and motivation to insert andremove the OA, as determined by a qualified dental profes-sional [1]. Certain baseline variables such as a younger age[5, 17–21], smaller neck circumference [22], supine-dependent OSA [21, 23], and sufficient amount of mandib-ular protrusion [24–28] are related to better treatmentresponses. In a 10-year OA follow-up study, lower bodymass index (BMI) did not seem to be related to long-termsuccess [29] which did not agree with other studies [5,19–21, 28]. Baseline AHI also played a controversial rolein predicating the OA efficacy; some report that lower AHIscores were related to a greater improvement in OSA [5, 17,19–21] while others demonstrate reasonably good successrates in patients with more severe OSA [18, 22, 28, 30–32].This controversy may be explained by different inclusioncriteria, treatment success definitions, OA design character-istics (titratable versus non-titratable), and/or different treat-ment protocols.

Based on a nasopharyngoscopic evaluation, mandibularadvancement was associated with enlargement of the velo-pharynx, with relatively minor changes occurring in theoropharynx and hypopharynx for OA responders [33]. ACT scan study did not find any significant correlationbetween upper airway variables and baseline/follow-upAHI, nor between the changes with OA therapy. Therewas no significant difference between good and moderateresponders in cross-sectional areas at the velopharynx andhypopharynx levels, hypopharynx to velopharynx ratio, andtotal upper airway volume before and during OA use [34].Since adults had larger, more elliptical, less uniform, andless compact airways than children based on CT data, the3D size and morphological changes in the upper airwayrelated to age may serve as a basis for evaluating patientswith OSA and may help to predict and evaluate treatmentoutcomes [35].

Comparison of efficacy

There are many studies which have attempted to comparethe overall treatment efficacy between different interven-tions for OSA. The focus has mainly been on the compar-ison of OA versus CPAP [36–39], active OA therapy versuscontrols [40–42], different types of OA therapy [27, 32,

43–45], or upper airway/maxillomandibular advancement(MMA) surgery [46, 47].

To date, there have been no published or well-acceptedindications or contraindications for each treatment modality,but practice parameter guidelines and standards are avail-able [5, 48, 49]. CPAP is more effective than OA in reduc-ing the AHI [17, 36, 37, 39, 50] since OA simply dilates theairway and does not provide air under pressure directly tothe lungs. Other articles did not find clinically relevantdifference between OA and CPAP in the treatment ofmild/moderate OSA when both treatment modalities aretitrated objectively [51, 52]. There was no significant dif-ference in baseline AHI between patients who preferred OAover CPAP [37]. With respect to improvements in symp-toms, quality of life, Epworth Sleepiness Scale (ESS), andcompliance, OA is similar to that of CPAP [39]. An OA isusually preferred in effective cases over CPAP due to its lessinvasive characteristics [52].

Based on the fact that definition of success/failure criteriain different studies was not uniform, the rates of reportedefficacy may be biased and varies from study to study [53].Some evidences showed that there was no one mandibularadvancement design that most effectively improves poly-somnographic indices [53, 54]. Others announced the effi-cacy depends on severity of OSA, materials and method offabrication, type of device (mono-block vs. twin block), andthe degree of protrusion (sagittal and vertical) [27, 43, 45,55, 56]. In a retrospective review, the titratable OAs werefound to be more superior to fixed (non-titratable) OAs intheir ability to reduce the AHI among a cohort of 805patients with a wide range of OSA severity although thefixed OAs were frequently successful in mild cases [19].Some researchers advised that pre-fabricated, over-the-counter appliances are less effective, less accepted, and notqualified as a screening tool to predict OA responders [45].

An OA or CPAP cannot be compared with surgicalprocedures in crossover studies due to the irreversible natureof the surgeries. In 2010, Sleep Medicine Reviews publisheda clinical review [57] of 53 reports (627 adults with OSA)showing that the mean AHI decreased from 63.9/h to9.5/h (p<0.001) following MMA surgery. This meta-analysis showed that a younger age, lower preoperativeweight and AHI, and greater degree of maxillary advance-ment were predictive of increased surgical success.Hoekema and co-workers [46] suggested that OA therapymight be a good predictor for the success of MMA surgeryin OSA management.

It is often difficult to decide which modality is superiorbecause patients vary in terms of initial perception, behav-ioral motivation, adherence, and facility accessibility. In thiscomplicated situation, who (i.e., a certain patient) is consid-ered prior to which (i.e., a certain therapy) when determin-ing what is the best choice. Table 1 lists the randomized

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Tab

le1

Rando

mized

controlledtrialsstud

iesregardingOA

advancem

ent,efficacy,side

effects,andcompliance

Reference

Study

design

OA/com

parator

Com

pleted

numbers

OA

titratio

n/advancem

ent

amount

Efficacy

Sideeffects

Com

pliance

Barnes

(2004)

[36]

RCT3-way

crossover

CPA

Pvs.OAvs.

placebotablet

114OSAS

(baselineAHI

21.3±1.3)

Mandibularadvancem

entwith

theOAwas

10.3±0.3mm

and

ranged

between1and13

mm.

77%

ofsubjectsachieved

atleast70

%of

maxim

umpossible

protrusion

Bothactiv

etreatm

entsim

proved

sleepoutcom

esbutCPA

Phadagreatereffect.Subjective

outcom

esim

proved

toasimilardegree

with

both

treatm

ents.Mostneuropsychologic

improvem

entswerenotbetterthan

the

placeboeffect

N/A

CPA

P:91.8

%;with

average

use4.2±0.3nights/week,

3.6±0.3h/night

3monthsper

period

CPA

P=97

OA:85.9

%;with

average

use5.3±0.3nights/week,

5.5±0.3h/night

2weeks

washout

OA=99

Placebo:91.8

%

Placebo

=98

Blanco

(2005)

[40]

Prospectiv

eRCT

parallel

3months

Softelastic

silicone

positio

ner(O

A)

vs.nonadvanced

mandiblemodel

(MND)

15/24OSAS

(13M

,2F

)OA:single

initial

advancem

ent

to75

%of

themaxim

umforced

advancewith

a5-mm

opening

AHIdecreased:

OA

(p<0.01);MND

(p<0.05);

ESS,snoring,

andfunctio

naloutcom

esof

sleepquestio

nnaire

significantly

decreased

only

intheOA

group

Excessive

saliv

ationnotcausing

abandonm

ent:OA=2

OA:7.7±0.5h/night

OA=8(baseline

AHI33.8±14.7)

5with

drew

dueto:

MND:6.5±1.4h/night

MND=7(baseline

AHI24.0±12.2)

Nausea:

OA=1;

MND=1

Appliancedisplacement:

OA=2;

MND=1

Deane

(2009)

[44]

RCT crossover

OAvs.tongue

stabilizing

device

(TSD)

27OSA

patients

(20M

,7F

)(baselineAHI

29.96±17.17)

OA:77

±8%

(2–10

mm)of

the

maxim

aljaw

protrusion

AHIandarousalindexweresignificantly

reduced

with

OA

andTSD.68

%of

patientsachieved

aresponse

with

OA

comparedto

45%

with

TSD

OA:jaw

discom

fort(59.1%)

anddrymouth

(50%)

Subjectivecompliancewas

betterforOA

(≥6h/night)

reported

by81.8

%of

patientscomparedwith

27.3

%forTSD

1weekper

period

TSD:non-adjustable,with

the

patient

controlling

theam

ount

oftongue

protrusion

andsuction

TSD:excess

saliv

ation(86.4%),

drymouth

(59.1%),and

soft-tissueirritatio

n(50%)

1week

washout

Dort

(2008)

[100

]

RCT crossover

TRD

with

activ

esuctionvs.non-

suctiondevice

(control)

32/38OSA

patients(22M

,10F)(baseline

RDI15.5±17.6)

N/A

TRD:RDIandsnoringindexsignificantly

reduced

Excessive

saliv

a,tender

oral

mucosaandtongue

were

resolved

spontaneously

54%

ofsubjectswishedto

continue

theTRD

1weekper

period

Control:no

significantchangesfound

1week

washout

Gotsopoulos

(2004)

[101

]

RCT crossover

OAvs.control

oral

appliance

61/74OSAS

(baselineAHI

27±15)

Meanadvancem

entof

mandible

with

theOA:7±2mm

Com

paredwith

control,OA

resultedin

50%

reductionin

meanAHI,im

proved

MinSaO

2and

arousalindex(p<0.05),andsignificantly

reduced

24-h

diastolic

BP(p=0.001)

butnot24-h

systolic

BP.

OA

significantly

reducedboth

awakediastolic

BP(p<0.0001)andsystolic

BP(p=0.003)

N/A

OA:6.8±0.1h/night

4weeks

per

period

OA

1st=

32Control:6.9±0.1h/night

1week

washout

Control

1st=

29Both:

97±1%

nightsduring

4weeks

Hoekema

(2007)

[38]

RCTparallel

OAvs.CPA

P47/48maleOSAHS

Initial

setting

at50

%of

the

maxim

umadvancem

ent.2-week

adaptatio

n.1–2increm

ents

(0.2–0.4mm)pernightfor

6-weekperiod

oruntil

symptom

sabated

orfurtheradvancem

ent

caused

discom

fort.The

mean

advancem

entwas

81±20

%of

themaxim

umadvancem

ent

Bothgroups

show

edsignificantim

provem

entsin

the

ESS,AHIandlowestoxyhem

oglobinsaturatio

nduring

sleep.

Neither

groupshow

edsignificant

improvem

entsin

sexual

functio

ning

N/A

Nosignificantdifferences

betweenthetwogroups.

OA

groupreported

using

treatm

entsignificantly

morehourspernight

(7.1±1.1)

whencompared

with

theCPA

Pgroup

(6.3±1.3)

2–3months

OA=20

(baseline

AHI9.5–

31.1)

CPA

P=27

(baseline

AHI10.0–64.6)

Lam (2

007)

[39]

RCTparallel

Non-adjustableOA

vs.CPA

Pvs.

91/101

OSAS

(baselineAHI

21.4±1.1)

OA

single

advancem

entat

the

mostadvanced

positio

nwith

out

AHIreduced:

OA

(p<0.05);CPA

P(p<0.001);

CM

(NS).SAQLIandmorning

diastolic

blood

CPA

P:drynessof

thenose,

mouth,or

throat

(47%);

feelingof

pressure

(32%);

CPA

P:4.4±0.1nights/week;

4.2±0.1h/night

Sleep Breath

Tab

le1

(con

tinued)

Reference

Study

design

OA/com

parator

Com

pleted

numbers

OA

titratio

n/advancem

ent

amount

Efficacy

Sideeffects

Com

pliance

conservativ

emeasures(CM)

causingdiscom

fortwith

some

vertical

opening

pressure:significantly

improved

inboth

OA

and

CPA

Pwith

nodifference

betweenthetwogroups

noisefrom

machine

(24%);

facial

skin

abrasion

(21%)

10weeks

OA=30

OA:excessivesaliv

ation(56%);

TMJdiscom

fort(38%);

drynessof

thethroat

(33%);

toothdiscom

fort(33%)

OA:5.2±0.3nights/week;

6.4±0.2h/night

CM=28

1/34

CPA

Pwith

drew

dueto

intolerance

CPA

P=32

4/34

OAwith

drew

dueto

gum

problems

Naism

ith(2005)

[102

]

RCT crossover

OAvs.inactiveoral

device

(control)

73/86OSA

Given

acclim

atizationphaseof

8.3±4.1weeks,themandible

was

increm

entally

advanced

tothemaxim

umcomfortable

limitof

advancem

ent

OA:55

%reductionin

AHIcomparedwith

control,

OA

improved

AHI,AHI–REM,AHI–NREM,

minSaO

2,arousalindex,

ESS,fatig

ue–inertia

(p<0.01);andvigor–activ

ity,somatic

items(p<0.05)

N/A

N/A

4weeks

per

period

OA

1st=

36(baseline

AHI27.9±17.5)

1week

washout

Control

1st=

37(baselineAHI

25.9±13.2)

Petri (2008)

[103

]

RCTparallel

OAvs.mandibular

non-advancem

ent

appliance(M

NA)

vs.no

interventio

n(N

I)

81/93OSAS

OA

single

advancem

ent:mean

protrusion

74%

(64–85

%)

ofthedifference

betweenthe

retrusivepositio

nandthe

maxim

alprotrusion

OA:reducedAHI(p<0.001),reducedESS

(p<0.001),im

proved

vitality(p<0.001),im

proved

MCS(p<0.05),andim

proved

mental/g

eneral

health

(p<0.05).MNA:no

placeboeffect

FourOA

patients(14.8%)and

twoMNA

patients(8

%)

discontin

uedinterventio

nsbecauseof

adverseeffects:

87%

ofpatientscompleted

thetrail

4weeks

OA=27

(baseline

AHI39.1±23.8)

Not

tolerate

theappliance:

OA=2,

MNA=1

MNA=25

(baseline

AHI32.6±22.0)

Loosening

oftheteeth:

OA=1,

MNA=1

NI=

29(baseline

AHI34.3±26.3)

TMJpain:OA=1

Vanderveken

(2008)

[45]

RCT crossover

Mono-bloc

thermoplastic

OA

(MADtp)vs.

custom

-madeOA

(MADcm)

35OSA

patients

(baselineAHI

13±11)

(29M

,6F

)

N/A

AHIsignificantly

reducedwith

MADcm.NoAHI

effect

with

MADtp

Sideeffectscausing

discontin

uatio

n:Com

pliancerate:MADtp:

69%,notrecommendedas

therapeutic

optio

nMADcm:94

%4monthsper

period

TMJor

toothpain:MADcm=2;

MADtp=1

1month

washout

Lackof

retention:

MADtp=8

Sleepingproblem

ordiscom

fort

atnight:MADtp=2

Walker-

Engstrom

(2002)

[47]

RCTparallel

OAvs.UPPP

72/95maleOSA

The

meanmaxim

umprotrusive

capacity

was

thesame,9.7mm,

atthe4-year

follo

w-upas

before

treatm

ent.Nopatient

changed

theirprotrusive

capacity

>2mm

63%

oftheOA

groupattained

norm

alization(A

I<5

orAHI<10),while

thenorm

alizationrate

forthe

UPPPgroupwas

33%

Success

(≥50

%reduction

inAI)rate

was

significanthigher

intheOA

group(81%)than

theUPPPgroup(53%)

OA:few

adverseeffectson

the

stom

atognathic

system

with

amoderatenumberof

adjustments

andrepairsover

time

Com

pliancerate

forOAwas

62%.75

%of

theUPPP

groupcontinuedwith

out

complem

entary

treatm

ent;

25%

startedto

usethe

dental

applianceas

complem

entary

treatm

ent

afterthe1-year

follo

w-up

4years

OA=32

(baseline

AHI17.9)

UPPP:complaintsof

nasopharyngeal

regurgitatio

nof

fluid(8

%)anddifficulty

with

swallowing(10%)

UPPP=40

(baseline

AHI19.9)

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controlled trials (RCT) that compared individual therapy regard-ing OA advancement, efficacy, side effects, and compliance.

Titration protocol

Since the titratability and the degree of protrusion are con-sidered to be related to the efficacy of an OA, some articlesevaluated titration protocols for specific OAs. Clinically, thetitration starting point and technique vary with the OA typeand the patient’s ability to protrude the mandible [58]. Thesuccess of titration is dependent on the clinician’s experi-ence and determined by subjective feedback from the patientand their family members. The usual advice is to stoptitration when the patient or bed partner reports a cessationof snoring, a resolution of symptoms, or finds furtheradvancement uncomfortable [59]. In fact, the use of onlysymptomatic responses to finalize titration can on occasionleave a patient with residual sleep apnea on a PSG [60].Determining the effective protrusive setting for an OA usuallytakes place over several months and may involve multiplevisits to the dental practitioner’s office [61]. In-laboratoryPSG is still believed to be a good method for optimizing thetitration end point. Some studies [61, 62] used titration toolsduring a PSG in order to provide an optimal advancementmeasurement as a guide for the patients. One-night mandibu-lar advancement was advocated to achieve the best possibletherapeutic dose of advancement more rapidly and has thepotential to predict the response from an individual patient[63, 64]. Ambulatory monitoring devices with limited chan-nels are also suggested in order to detect the titration end point[65, 66]. These issues need to be further studied to quantifytheir therapeutic usefulness.

A follow-up PSG after titration is routinely indicated as aparameter standard by AASM in order to confirm the clin-ical response to OA treatment in patients with moderate tosevere OSA and to ensure therapeutic benefit [4]. In reality,the follow-up PSG is rarely performed due to various rea-sons such as insurance coverage and/or sleep laboratoryavailability. Table 2 summarizes some titration strategiesand evaluates the benefits of each method.

Side effects and managements

The side effects of OA therapy differ depending upon theindicated individual titration amount and patient manage-ment. Although the significance of AHI improvement pro-portionally relies on the amount of mandibular advancement[26], it has been suggested that more titration would lead tomore side effects [65].

Short-term side effects such as hypersalivation, mucosaldryness or irritation, tooth discomfort, morning occlusalchanges, myofascial stiffness, and/or temporomandibular

discomfort are mostly transient or minor and resolutionsare reported within several days to several weeks withcontinued adaption to OAs [45, 65, 67]. More severe andcontinuous side effects in the titration/initial treatmentstage may include tooth movements, occlusal changes,gingival pain, and temporomandibular and/or myofascialdiscomfort. These side effects, if not addressed andcorrected by the dentist, can be one reason for discon-tinuing treatment.

Side effects over a long period of time are common andnon-preventable but are usually mild and well tolerated bymost patients [26, 68]. An evidence-based review [20] sum-marized side effects and complications from 38 publishedstudies (over 1,700 patients evaluated) concluded that minoradverse effects were frequent whereas major adverse effectswere uncommon while using OAs. The topics that are ofgreatest concern to dentists are listed below.

Dental/occlusal/skeletal changes

Robertson and co-workers [69] recorded that changes inface height, the position of the mandible, overjet, and over-bite occurred as early as 6 months, whereas over-eruption ofthe maxillary first premolars and mandibular first molarsand proclination of the mandibular incisors were not evidentfor at least 2 years. Five-year OA therapy may be associatedwith permanent occlusal changes [68, 70, 71]. The patientswith the original greater overjet and/or overbite appears tohave the most favorable occlusion changes after long-termtherapy based on cephalometric and model analysis [68, 71].In other words, dental changes may result in favorablereductions in overjet and/or overbite in Angle Class II,Division 1 (mandibular retrognathism with protrusive max-illary anterior teeth) patients. A prospective and randomizedstudy [72] revealed the overjet, overbite, and mandibularlength in 63% cases who on average had 50% maximal jawadvancement did not show significant changes after 4 yearsof wearing an OA. This agrees with Hammond andco-workers who regard dentofacial changes as negligiblefor long-term users [73]. Monitoring of occlusal changesin 45 patients (≥4 days/week for over 5 years) identified 39patients with changes in occlusion detected by a dentalprescale pressure-sensitive sheet [74]. Even unfavorabledental side effects in terms of jaw position should not beconsidered a contraindication to OA therapy since occlusalchanges are most often adapted to and accepted by patientswhen compared with the consequences of life-threateningOSA [71]. A recent study documented that the use of CPAPmachine for over 2 years may change craniofacial form byreducing maxillary and mandibular prominence and/or byaltering the relationship between the dental arches [75]. Thisis the first study that shows not only OA but also CPAPcould cause subtle dental and skeletal changes since the

Sleep Breath

Tab

le2

OA

titratio

nprotocol

summary

Reference

Study

design

OA

type

Titrationstrategy

Com

ments

Aarab

(2010)

[65]

17OSA

patients(m

eanAHI21.6±11.1)

underw

entfour

PSGswith

theirOA

insitu

at0%

,25%,50%,and75%

ofthe

maxim

umprotrusion

toassess

the

influenceof

four

mandibularprotrusive

positio

nsat

aconstant

vertical

dimension

Mandibular

advancem

ent

device

The

OAwas

setat

aconstant

vertical

openingof

6mm

betweenthefirstincisors

with

theOA

inthemouth.The

patientswereaskedto

undergofour

ambulatory

PSG

recordings

athomewith

theOA

insitu

at0%

,25%,50%,

and75%

ofthemaxim

umprotrusion

inarandom

order.

The

averageinterval

duratio

nof

3weeks

between

subsequent

recordings

was

required

The

meanAHIvalues

differed

significantly

betweenthe

protrusion

positio

ns.T

he25%

protrusion

resultedin

asignificantreductio

nof

theAHIwhilein

the50%

and75%

protrusionseven

lower

AHIvalues

werefound.The

number

ofside

effectswas

greaterstartin

gatthe50%

protrusive

positio

nso

thisam

ount

ofstartin

gprotrusion

was

recommended,beingaweightedcomprom

isebetween

efficacy

andside

effects

Alm

eida

(2009)

[60]

Retrospective

study;

23OSA

subjects

(17M

,6F

)(m

eanAHI36.2±21.7)

AdjustablePM

Positioner™

Initialadvancem

ent:60%

ofmaxim

ummandibular

advancem

ent.Patientsstartedto

advanceon

the2ndweek

with

0.5mm

every3nightsuntil

thesymptom

snorm

alized.

TitrationPSGmonito

redwith

theOAin

place.The

PSG

technician

assisted

patientsobtain

upto

3mm

more

advancem

entifnecessarybasedon

AHI

Success

rate

(AHI≤1

0associated

with

atleasta50%

reductionin

AHI):65.2%.17.4–30.4%

(depending

upon

differentsuccesscriteriachosen)of

patientswere

incompleteresponders

andonly

successfully

treatedafter

titratio

nPSG.The

averagetim

ebetweeninsertionof

the

OA

andthetitratio

nPSG

was

5.8months.Eight

subjects

required

in-lab

advancem

ent(m

ean2.7mm)

Dort

(2006)

[61]

33OSA

patients(RDI26.9±18.3)

underw

entaremotelycontrolled

mandibularpositio

ner(RCMP)test

during

PSG

monito

ring

Mandibular

repositio

ning

appliances

The

mandiblewas

advanced

in1-mm

increm

entsin

stable

stage2sleep.

Ifan

EEG

arousaloccurred,no

further

advancem

entwas

attempted

until

stable

sleepreturned.If

thepatientsaw

okeandwas

unable

tofallasleep

with

in10

min,alladvancem

entwas

reversed

andre-initiated.

Otherwise,theadvancem

entcontinueduntil

elim

inationof

apneas,h

ypopneas,and

nocturnaloxygen

desaturatio

nwas

achieved

The

RCMPtestwas

asuccessin

15subjectsandafailu

rein

18subjects.The

OA

therapywas

successful

attarget

protrusion

in80%

ofsubjectswho

hadasuccessful

RCMP

testandfailedin

78%

ofthosewho

failedtheRCMPtest

Gauthier(2009)

[43]

RCTsingle

blindcrossover;12

weeks

per

period,5females

and11

males

with

OSA

(RDI9.4±1.1)

Silencer

vs.

Klearway™

Silencer:initial

advancem

entof

50%

ofmaxim

alprotrusion;

twoadvancem

entsof

2mm

each

madeby

thedentistat

4and8weeks.Klearway:initial

advancem

entof

75%

ofmaxim

alprotrusion;selfadvancem

entstwiceaweekand

verified

bythedentistevery4weeks

BothOAssignificantly

reducedtheRDI.Subjects’

preferenceswerein

favorof

theKlearway.The

Epw

orth

score,FOSQ,respiratorynoise,andmorning

headaches

werealso

improved

follo

wingtheuseof

both

appliances

Ghazal

(2009)

[80]

103OSA

patientswererandom

ized

and

treatedwith

twotypesof

OA

(baseline

AHI32

±6and37

±8).The

follo

w-up

sleepstudiesin

thesleeplaboratory

were

conductedwith

andwith

outtheappliance

after6months(shortterm

)andover

24months(longterm

)

IST®

(amodified

Herbstappliance)

vs.TA

P™

(Thornton

Anterior

Positioner)

IST®:constructio

nbite

at75%

ofmaxim

umprotrusion

(5±

2mm).TA

P™:increase

theprotrusion

in1–

3-mm

stepsif

patient

was

dissatisfied

with

thetherapyafterthefirst

2months.Protrusionwas

reducedin

stepsof

1–3mm

upto

halfof

width

ofabicuspid

ifdiscom

fortwas

reported

Qualityof

life,sleepquality,sleepiness,symptom

s,andsleep

outcom

esshow

edsignificantimprovem

entintheshort-term

evaluatio

nwith

both

OAs.TA

P™

revealed

asignificantly

greatereffect.T

helong-term

sleepoutcom

esrevealed

anequaleffectw

ithboth

OAs

Gindre

(2008)

[26]

66OSA

patients(m

eanAHI38.6±20.3)

underw

entPSGsat

baselin

eandat

the

finalmandibularadvancem

entandlim

ited

sleeprecordings

during

progressive

mandibularadvancem

enttitratio

n

AMC™

Initial

advancem

ent:80%

ofmaxim

ummandibular

advancem

entadjusted

with

semi-adjustable

articulator

1mm

every2weeks

until

AHI<10

orattainmentof

the

maxim

umcomfortable

limitof

advancem

entwas

achieved

70%

ofpatientsneeded

asingletitrationwith

amarkeddecrease

inmeanAHIfrom

36to10.30%

ofpatientsneeded

multiple

titrations

with

aprogressivereductioninAHI.Im

provem

entin

AHIduring

OAtherapyisdependentupontheam

ountof

mandibularadvancem

ent

Krishnan(2008)

[18]

Retrospective

study;

57OSA

subjects

(meanbaselin

eAHI=

24.8)treated

with

OA

Mandibular

repositio

ning

appliances

Hom

eself-titrationuntil

symptom

resolutio

nor

discom

fort.

Additionaltitratio

n(≤1mm)was

performed

asneeded

dependingon

thefollo

w-uptitratio

nPS

G.T

wentyminutes

ofsleepafteratitratio

nor

sleeppositio

nchange,and

ifnotin

rapideyemovem

entsleep,the

OAwas

advancein

1-mm

increm

entsor

less

ifnottolerated

andPS

Gcontinued.The

optim

almandibularposition

wasdeterm

ined

bythereview

ing

sleepphysicianandsleep-traineddentist

64.9%

ofsubjectsregardless

ofOSA

severity

were

successfully

treated(defined

asAHI<10

anddecreased

≥50%

from

baselin

e)with

OAT.

55%

ofthesubjects

achieved

successful

treatm

entby

self-titrationwith

outthe

need

forfurthertitratio

nduring

follo

w-upPSG.The

majority

ofsubjects,regardless

ofOSA

severity,are

successfully

treatedwith

anOA.M

enandyoungerpatients

werefoundto

bethebestresponders

Sleep Breath

CPAP mask and straps are designed to be tightened on thenose and face region to avoid air leakage.

Temporomandibular joint/jaw muscle complications

Since the patient’s mandible is held in a forward positionduring sleep, it is predictable and has been substantiated bysome studies [39, 44, 76] that OAs may cause jaw discom-fort or pain especially during the early stages of use. TheOA therapy resulted in more pain of the temporomandibularjoint (TMJ) complex compared to CPAP therapy in a paral-lel randomized controlled study [76], but the transient natureof the initial TMJ pain was not considered a reason tocontraindicate an OA in OSA patients. Other researchersreport that the intensity of TMD symptoms decreases sig-nificantly throughout treatment among patients who are ableto continue use of the OA [25, 70, 76, 77]. The improve-ment of TMJ monitoring and management is recommended,although there is no scientific evidence suggesting consis-tent undesirable long-term effects of OA on the TMJ.

A crossover study compared the efficacy of a reinforcedadjustable OA and a mandibular occlusal splint on sleepbruxism found that the OA reduced sleep bruxism episodesto a greater extent than a splint alone. It concluded that thereinforced OA design may be an alternative for patients withconcomitant tooth grinding and snoring or apnea duringsleep [78].

There are very few articles designed to investigate how toease the temporomandibular/myofascial complications. Ifthe problems cannot be solved due to the jaw not settlingback to its regular position throughout the day, someresearchers suggest certain jaw exercises (jig exercise andstretching movements) to relieve the occlusal function im-pairment [79]. Ten patients were recruited to do either of theexercises with 1-month wash-out and found that both exer-cises produced significant increases in occlusal contact areaand bite force in the morning compared with the period ofno exercise. There was no significant difference between thetwo exercises although the jig exercise tended to be moreeffective in the anterior region while the stretching move-ments tended to more effective in the molar region. Thestudy did not answer the question if these exercises enablemore aggressive advancement by counteracting the occlusalside effects. More evidence-based clinical trials with largerpatient pools are required to help more patients to benefitfrom OAs with less discomfort.

Compliance of OA

Long-term compliance is usually determined by follow-upquestionnaire studies. Response rates to the mailed ques-tionnaires were reported of 40–46.1% due to the patientsT

able

2(con

tinued)

Reference

Study

design

OA

type

Titrationstrategy

Com

ments

Kuna

(2006)

[24]

21OSA

patients(m

eanAHI33.5±18.3)

underw

entbaselin

e,titratio

nappliance

(EMA-T),andOA

PSGs

Klearway™

Duringthetitratio

nPSG

with

EMA-T,themandiblewas

advanced

in3-mm

increm

entsuntil

apneas

andhypopneas

wereelim

inated

orthemaxim

umtolerableadvancem

ent

was

reached.

The

participantsthen

used

theOAathome.A

PSG

with

OAwas

performed

once

themandiblewas

advanced

totheam

ount

determ

ined

during

thetitratio

nPSG

Based

ontheposthocmeasurementson

theGalletti

articulator,

maxim

ummandibularadvancem

entachievedwith

the

titratio

nappliancewas

7.8±1.8mm.T

hisam

ount

ofmandibularadvancem

entw

as85.2±25.8%

ofmaxim

alvoluntaryadvancem

ent.9subjectsachieved

anAHI<10

and

≥50%

reductioninAHI.EMA-T

lowered

theAHIacutelybut

nolong-term

predictio

ncouldbe

achieved

Tsuiki(2004)

[59]

20maleOSA

patients(m

eanAHI

31.6±13.0)received

PSG

andsupine

cephalom

etry

before

andaftertitratio

n

Klearway™

Initial

advancem

ent:67%

ofthemaxim

umprotrusion.Once

patientswereaccustom

edto

wearing

theOAwith

outany

discom

fort,they

startedadvancingthemandiblein

gradual

increm

entsof

0.25

or0.5mm

perweekuntil

any

discom

fortoccurred

orpatient/bed

partnerreported

acessationof

snoringandaresolutio

nof

symptom

s

The

meanAHIwas

significantly

decreased(9.8±7.4)

after

titratio

n.Thistitratio

nprotocol

reducedOSA

severity,

enlarged

thevelopharynx,

anddiminishedthecurvatureof

theanterior

velopharyn

geal

wallin

good

responders

Sleep Breath

unwilling to return the questionnaires or not updated theiraddress to their dental provider [29, 68]. Lost contactpatients could be considered non-compliant because theybecome less interested in re-call exams. A survey of 180OSA patients who had been using a OA for 10 yearsreported a 65% compliance rate; 47% wore the device everynight and 18% wore the device up to six nights per week[29]. The titratable adjustable OA made from thermoelasticacrylic was worn for a mean of 6.8 h with a range of 5.6 to7.5 h per night [30]. Lack of compliance may be due to aninsufficient improvement in anticipated subjective symp-toms and/or a recurrence of symptoms over time [80]. Ithas been shown that the initial discomfort of masticatorymuscles or the temporomandibular joint is a possible reasonfor poor compliance or abandonment of OA treatment [25,73, 81, 82]. Some other studies state that transient sideeffects do not require the discontinuation of treatment ifthey are well managed [22, 83].

The OAs that allow lateral jaw movement and verticalopening may reduce the risk of adverse effects and thusenhance patient adherence [84]. The amount of bite openinginduced by OAs does not have a significant impact ontreatment efficacy but does have an impact on patientacceptance, with the larger interincisal opening (14 mmversus 4 mm) significantly decreasing the patient’s prefer-ence [85]. Although there is still uncertainty about theinfluence of OA design on treatment outcomes, adverseeffects, adherence to treatment, and potential long-termcomplications of therapy [6], OA selection needs to be takeninto account when considering the benefit of the AHIreduction versus the subject’s compliance [43].

OA therapy in pediatric OSA

Increasing attention has been paid to children with OSA indentistry [86]. The polysomnographic diagnostic criteria forOSA in children are different than adults: an AHI >1 andoxygen desaturation ≥4% are indicators of mild OSA amongthose under 15 years of age [87]. Pediatric OSA can occur inany age group, including infants, with a peak incidencebetween the age of 2 and 8 years old, which correlates withthe age during which adenotonsillar hypertrophy is mostmarked. Increasing prevalence has also been noted in mid-dle childhood and adolescent age groups due to the risingprevalence of obesity in these age groups in some parts ofthe world [88].

When investigating prevalence, predication, sleep quali-ty/duration, daytime sleepiness, and performance in chil-dren, most articles use unique sleep questionnaires[89–91]. The questionnaires usually were answered by thechild’s parents or school teacher based on judgments andcomparisons with siblings or classmates of the same age. So

the screening examination for the SDB in childhood wasrelatively subjective but the ambulatory monitoring mighthelp to remedy this situation in the future [92].

Due to a lack of standard diagnostic resources and ongo-ing changes in a child’s anatomy and physiology frominfancy to adolescence, therapeutic strategies for childhoodOSA remain challenging. Unlike adult patients who mayundergo uvulopalatopharyngoplasty (UPPP) and MMA sur-geries, surgeries such as adenotonsillectomy or tonsillarpillar manipulation are generally considered to be the stan-dard treatment for childhood sleep apnea to relieve airwayobstruction in the retroglossal region, the nose, and/or theretropalatal area [93, 94].

Children with craniofacial abnormalities resulting inmaxillary or mandibular insufficiency may benefit fromOA or surgery [86, 95]. There is no long-term report onwhether childhood jaw surgeries cause alterations in jawgrowth. Some investigators encourage that if the signs andsymptoms of SDB had been noticed, the young patientshould be referred to a sleep medicine specialist in conjunc-tion with an orthodontist if there are dentoskeletal abnor-malities [92].

Rapid maxillary expansion (RME), as a powerful ortho-pedic OA for maxillary transverse deficiency, was found tobe a useful approach in dealing with abnormal breathingduring sleep in children. Pirelli and co-investigators [96]recruited 31 children with OSA in addition to maxillaryconstriction using RME to expand the maxilla for10–20 days followed by orthodontic treatment for 6 to12 months. They found the mean AHI was decreased from12.2±2.6 to 0.4±1.1 events/hour. The investigators were notsure if the study indicated the RME should be the firsttreatment approach for the children with adenotonsillarenlargement because they only enlisted the subjects withabsence of adenotonsillar hypertrophy. A systematic reviewevaluated 15 articles based on inclusion criteria and con-cluded that RME improved nasal breathing for an average of11 months of stability [97]. The review also indicated thatall the studies selected had methodologic deficiencies suchas less randomization and a lack of double-blindedinvestigation.

An OA is probably more conservative and predictable asit has a similar mechanism as an orthodontic functional fordeveloping children. The treatment procedure also requiresa sleep study in addition to the same baseline records (ceph-alometric and panoramic X-rays, study models, intra-/extra-oral photos) as used in traditional orthodontic patients. Intwo 6-month trials on children OSA patients treated withtwo types of OA [98, 99], both found significant improve-ment on AHI in OSA subjects. The initial problems with useof the OAs were salivation [98, 99] and discomfort onwaking [98] which gradually diminished after a few daysof wear. A pilot study at the University of British Columbia

Sleep Breath

orthodontic program demonstrated that selected Class II,Division 1 pediatric snoring/OSA patients undergoing OAtreatment had a fast adaptation, different titration strategy,accommodated the mixed to permanent dentition transition,rapid tooth movement, and had exhibited both tissue-bornein addition to tooth-borne retention. The outcome of suchtreatment over a long term is under investigation includingits impact on growth development.

Conclusion

In summary, an OA for OSA requires full documentation ina medical/dental history, and a sleep study to be able toselect prospective candidates. OA therapy is not a cure butappears to be an important treatment option for OSApatients who meet indications for this therapy. Further ran-domized controlled trials on OAs for pediatric patients needto be designed and investigated. Dentists who are responsi-ble for treating OSA and/or snoring may need to upgradetheir knowledge in dental sleep medicine. Sleep physiciansalso may need to further develop a working relationshipwith dentists to provide more treatment options for diag-nosed patients. Titration and side-effect management as wellas close follow-up during OA treatment are keys to achievecompliance and treatment success over the long term. Long-term OA outcome investigations require efficient patientinformation update systems and more objective measure-ments should be taken into consideration during assess-ments of covert compliance.

Acknowledgment The authors would like to thank Mrs. Ingrid Ellisfor her editorial assistance in the final preparation of this manuscript.

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