Biomimetic Oral Appliance Therapy in Adults with Mild to Moderate Obstructive Sleep Apnea

Abstract

Introduction: While Continuous Positive Airway Pressure (CPAP) is widely used to manage Obstructive Sleep Apnea (OSA), compliance can be problematic in some cases. These patients are often referred for Mandibular Advancement Devices (MADs) but there is less evidence of their efficacy in severe cases. We investigated the use of biomimetic oral appliance therapy (BOAT) to test the hypothesis that severe cases of OSA can be addressed using BOAT.
Materials and Methods: 15 consecutive adults aged >21 yrs with severe OSA that were unable to comply with CPAP according to a medical physician were treated using BOAT with or without primary mandibular advancement by a dentist with advanced training in dental sleep medicine. The mean Apnea-Hypopnea Index (AHI) of the sample was calculated prior to and after BOAT with no appliance in the mouth during the sleep studies. The findings were subjected to statistical analysis, using paired t-tests.
Results: Prior to treatment the mean AHI of the study sample was 45.9 hr-1 ± 10.5. A follow-up sleep study at 9.7 mos. ± 1.9 showed a 64% decrease in AHI to a mean value of 16.5 hr-1 ± 8.8 after BOAT (p<0.01) with no appliance in the mouth during the post-treatment sleep studies. Results for those without primary mandibular advancement were: 46.6 hr-1 ± 12.9 pre-treatment vs. 13.9 hr-1 ± 10.5 after BOAT (p<0.01); and for those treated with initial mandibular advancement: 45.2 hr-1 ± 8 pre-treatment vs. 19.5 hr-1 ± 6 after BOAT (p<0.01).
Conclusions: BOAT may be a useful method of managing severe cases of OSA in adults, and represents an alternative to CPAP and MADs. However, long-term follow up is needed to reach more definitive conclusions on these initial findings.

Full text

Citation: Singh GD, Grifn TM and Chandrashekhar R. Biomimetic Oral Appliance Therapy in Adults with Mild to
Moderate Obstructive Sleep Apnea. Austin J Sleep Disord. 2014;1(1): 5.
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Austin Journal of Sleep Disorders
Open Access
Abstract
Introduction: For the management of obstructive sleep apnea (OSA) in
adults, some professionals prescribe continuous positive airway pressure
(CPAP) while others prefer mandibular advancement devices (MADs). However,
both CPAP and MADs represent life-long therapy. In this study, we investigated
the use of a biomimetic oral appliance system (the DNA appliance® system) to
test the hypothesis that the upper airway can be improved in adults that have
been diagnosed with OSA.
Methods and Sample: We recruited 10 consecutive adults for this study
who underwent an overnight sleep study, which was interpreted by a sleep
physician. Subjects diagnosed with mild to moderate OSA were treated using
biomimetic oral appliance therapy (BOAT). Each subject had monthly follow-
up visits, including examinations for progress and adjustments of the devices.
The mean AHI of the sample was calculated prior to and after BOAT with no
appliance in the mouth. The ndings were subjected to statistical analysis.
Results: The mean treatment time was 8.7 mos. ± 5.8. Prior to treatment
the mean AHI was 13.2 ± 7.2. The mean AHI fell by 65.9% to 4.5 ± 3.6 (p =
0.021) after BOAT with nothing in the mouth when the nal overnight sleep study
was performed.
Conclusion: This preliminary study suggests that BOAT may be able to
reduce the AHI to within normal limits perhaps to the extent that life-long therapy
may not potentially be necessary. However, long-term follow up is needed to
determine whether these subjects need a maintenance program to retain their
initial upper airway improvements.
Keywords: Oral appliance therapy; Biomimetic; Obstructive sleep apnea;
Mandibular advancement device
the MAD group. In contrast, more patients withdrew from treatment
due to side eects in the CPAP group compared to the MAD group.
Nevertheless, while there is a large amount of evidence to support
the use of MADs for the management of mild to moderate OSA, and
while numerous cases have been treated successfully, there are some
concerns about the unwanted side-eects of MADs. For example,
Do et al. [3] reported signicant dental changes compared with
CPAP use, concluding that MADs should be considered as a lifelong
treatment with a risk of dental side eects. Earlier, Do et al. [4] had
found that, compared to CPAP, MADs are associated with increased,
transient pain in the temporo-mandibular joint (TMJ) in the initial
period of use, which they presumed would remain limited with long-
term MAD use.
On the other hand, Tsuda et al. [5] used a questionnaire to study
compliance and side eects of non-customized MADs. e majority of
the study sample had previously used CPAP therapy. Approx. 80% of
non-compliant subjects discontinued MAD use aer about 3 months.
e most frequent reasons for non-compliance with non-customized
MADs were discomfort, dry mouth, excessive salivation and ill-
tting appliances. us, long-term or lifelong, non-customized MAD
therapy may not be possible in all adults diagnosed with OSA that are
CPAP-intolerant. On the other hand, de Almeida et al. [6] quantied
Abbreviations
OSA: Obstructive Sleep Apnea; MAD: Mandibular Advancement
Device; CPAP: Continuous Positive Airway Pressure; AHI: Apnea-
hypopnea Index; DNA appliance: Daytime-Nighttime Appliance;
BOAT: Biomimetic Oral Appliance erapy; TMJ: Temporo-
mandibular Joint; SWS: Slow Wave Sleep; REM: Rapid Eye Movement
Introduction
For the management of obstructive sleep apnea (OSA) in adults,
some healthcare professionals prefer to prescribe continuous positive
airway pressure (CPAP) masks while others prefer mandibular
advancement devices (MADs). White and Shafazand [1] assessed
whether MADs had similar health outcomes to CPAP in the short
term. In terms of the primary outcomes e.g. improvements in blood
pressure, they reported no statistically signicant dierence between
the two types of therapy. However, neither treatment lowered the
blood pressure from baseline values in either group aer one month
of therapy. us, both CPAP therapy and MADs may represent
lifelong use. But earlier, Aarab et al. [2] investigated the ecacy of
both MAD and CPAP use. eir results indicated that while the initial
improvements in the AHI remained stable over time within both
groups, the AHI improved more in the CPAP group compared to
Research Article
Biomimetic Oral Appliance Therapy in Adults with Mild
to Moderate Obstructive Sleep Apnea
Singh GD1*, Grifn TM2 and Chandrashekhar R3
1BioModeling Solutions, Inc., Beaverton, USA
2Emerald Coast Dental Sleep Medicine, Panama City
Beach, USA
3Sleep Medicine, Ravindra Chandrashekhar Inc.,
Victorville, USA
*Corresponding author: Prof. Singh GD, BioModeling
Solutions, Inc., Cornell Oaks Corporate Center, 15455
NW Greenbrier Parkway, Commons Building, Suite 250,
Beaverton, OR 97006, USA, Tel: 971-302-2233; Fax: 866-
201-3869; Email: drsingh@drdavesingh.com
Received: August 29, 2014; Accepted: October 11,
2014; Published: October 16, 2014

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compliance and side eects of customized MAD use aer approx.
5.5 years in patients diagnosed with OSA. Over 60% of the sample
was still complying with MAD therapy but there was no signicant
dierence in the baseline and post-titration respiratory indices used
to assess the success of treatment if the appliance was not worn while
sleeping. e most frequent reasons why patients discontinued MAD
use were discomfort, or the MAD had no eect and the subject used
CPAP instead. Other side eects of customized MAD use included;
dry mouth, tooth pain, jaw discomfort, and TMJ symptoms. us,
subjects who were compliant with customized MAD for long periods
of use had adequate improvements as long as they continued wearing
the MAD.
Cohen-Levy et al. [7] measured forces created in patients wearing
MADs. ey reported an almost linear relation, with a mean force
of approx. 1Nmm-1 of mandibular protrusion, and this level of force
is similar to that used during adult orthodontic therapies. us,
the force values recorded in that study may explain both the dental
and skeletal side eects associated with long-term MAD use, in a
possible dose-dependent eect. Conversely, biomimetics is a science
that uses natural designs or mechanisms to solve human problems.
Accordingly, in a manner similar to orthodontic correction, the
judicious use of the vectors induced in oral appliance therapy might
provide an alternative protocol for the resolution of OSA, with the
upper airway being the target in mild to moderate cases. erefore,
the aim of this current study is to test the hypothesis that OSA can be
resolved in adults using a novel protocol that utilizes biomimetic oral
appliance therapy (BOAT).
Methods and Sample
Aer obtaining informed consent, 10 consecutive patients were
recruited for this study. e rights of the subjects were protected by
following the Declaration of Helsinki. Inclusion criteria were: adults
aged >21yrs. diagnosed with mild to moderate OSA following an
overnight sleep study that had been interpreted by a sleep physician;
good oral appliance compliance; no history of hospitalization for
craniofacial trauma or surgery; no congenital craniofacial anomalies,
and a fully-dentate upper arch. e exclusion criteria included:
age <21yrs.; lack of oral appliance compliance; active periodontal
disease; tooth loss during treatment; poor oral hygiene, and systemic
bisphosphonate therapy. e study protocol (#121310) was reviewed
and approved by the institution’s review board.
Aer careful history-taking and craniofacial examination, a
bite registration was obtained in the upright-sitting position with
corrected jaw posture in the vertical axis specic for each subject.
Upper and lower polyvinyl siloxane impressions were also obtained.
e upper model was then mounted on an articulator and the lower
model was mounted relative to the upper model, using the bite
registration captured in the physiologic rest position. Following a
diagnosis of mild to moderate OSA, a biomimetic, upper Daytime-
Nighttime Appliance (DNA appliance®; Figure 1) was prescribed
for each subject. e biomimetic oral appliance therapy (BOAT) is
designed to correct maxillo-mandibular hypoplasia in both children
and adults [8-16]. e biomimetic oral appliance used in this study
had: 6 (patented) anterior 3-D axial springsTM, a beaded pharyngeal
extension, a midline screw, bilateral occlusal coverage, retentive clasps,
and a labial bow (Figure 1a). All subjects were instructed to wear the
appliance during the evening and at nighttime (for approx. 12-16hrs.
in total), but not during the day time and not while eating, partly in
line with the circadian rhythm of tooth eruption [17] although this
only occurs in children. Prot [18] notes that an appliance needs to
be worn for at least 8hrs.in the mouth to have a clinical eect. Written
and verbal instructions were given to all subjects.
e BOAT needed to be professionally-adjusted approximately
every 4 weeks, and all subjects reported for review each month. At
each monthly follow-up, examination for the progress of midfacial
development was recorded. Adjustments to the devices were
performed to optimize their ecacy. Only gentle pressures were
transmitted to the teeth and surrounding tissues and the functionality
of the device was checked with the subject activating a mild force on
biting. e subjects were encouraged to maintain their treatment
regimen as outlined at the outset. Development of the lower arch
was implemented using a lower appliance (Figure 1b) to permit arch
re-coordination. A lower appliance (Figure 1b) was implemented
between 1 to 3 months aer the upper appliance, depending on the
subject’s progress. Every 3 months, the overnight sleep studies were
repeated. e post-treatment sleep tests were done with no appliance
Figure 1a: The upper acrylic-based Daytime-Nighttime Appliance (DNA
appliance®) that was used in this study consisted of: 6 (patented) anterior
3-D axial springsTM; a midline jackscrew; bilateral posterior occlusal rests;
bilateral retentive clasps, a short labial bow with U loops, and an adjustable,
beaded pharyngeal extension.
Figure 1b: The lower acrylic-based Daytime-Nighttime Appliance (DNA
appliance®) that was used in this study consisted of: 6 (patented) anterior
3-D axial springsTM; a midline jackscrew; bilateral retentive clasps, and a short
labial bow with U loops.

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in the mouth and were interpreted by a sleep physician. e mean
apnea-hypopnea index (AHI) of the study sample was calculated
prior to and aer BOAT and the ndings were subjected to statistical
analysis, using paired t-tests.
Results
One subject was excluded from the study as the age was <21yrs,
leaving a nal sample of 6 females and 3 males. e mean age of the
sample was approx. 54.5 yrs. and the treatment time of the study
sample was 8.7 mos. ± 5.8. Prior to treatment the mean AHI of the
sample was 13.2 ± 7.2. e mean AHI fell by 65.9% to 4.5 ± 3.6 (p
= 0.021) aer BOAT with no appliances in the mouth during sleep
when the post-treatment sleep study was undertaken, indicating
enhanced upper airway function. ese results are summarized in
Table 1 and Figure 2.
Discussion
Both CPAP therapy and MADs represent lifelong use for the
treatment of OSA, but the upper airway is a complex, adaptive
system, which can undergo remodeling in pathologic conditions
[19]. Similarly, pneumatization following bone remodeling is a
well-known craniofacial phenomenon [20-21], but none of these
mechanisms have been applied to upper airway correction in patients
with OSA. For example, Gindre et al. [22] investigated dose-eect,
long-term use and tolerance of MADs used for OSA. When MAD
therapy was started at 80% of maximum mandibular protrusion,
the nal titrated position resulted in a 70% decrease in AHI but 17%
of the subjects showed no response. Aer 17 months of treatment,
approx. 80% of patients were still using a MAD on almost all nights
but the side eects reported, such as occlusal changes, were frequent.
Chen et al. [23] investigated occlusal changes that occur aer long-
term MAD use. ey found that a variety of occlusal alterations
occurred with long-term MAD therapy, and that these changes could
be regarded as adverse or benecial, depending upon the particular
case. For example, the mandibular arch width increased more than
maxillary arch in some cases; crowding decreased in both arches
in other cases; eruption occurred in the premolar area in others,
while the lower posterior segment moved forward in relation to the
maxillary arch in some patients. In addition, there were instances of
decreased overbite (bite opening) in some cases with decreases in the
overjet in others. us, rather than ignore or overlook these adaptive
changes, in this present study we utilized a clinical protocol that
putatively harnesses the corrective mechanisms of the craniofacial
system, similar to orthodontic treatments. Indeed, increases in 3D
midfacial bone volume aer BOAT have been reported in adults
[15] and initial studies conrming increased nasal cavity volumes
have also been found aer BOAT in adults [16]. us, the target of
correction in this study is the upper airway, and the intention of this
study was to determine whether BOAT might be advantageous as an
alternative to MADs and CPAP in the management of patients with
mild to moderate OSA.
Upper airway correction is associated with improved sleep
architecture. For example, patients treated with CPAP for OSA have
been reported with a rebound of slow wave sleep (SWS) and rapid eye
movement (REM) sleep rebound, which results in an improvement
in sleep quality [24]. Indeed, it appears that REM rebound, but not
SWS rebound, is associated with CPAP compliance [25]. Although
a 20% increase in REM sleep has been proposed as a threshold to
identify REM rebound, one study reported >70% REM sleep of the
total sleep time. However, the large REM rebound in that case could
have been due to additive eects of CPAP therapy and suspension
of anti-depressive treatment [26]. Nevertheless, while rebound of
SWS and REM is observed in patients who are on CPAP therapy for
OSA, neither has been objectively dened. But, rebound SWS and
rebound REM can be predicted by abnormal sleep architecture/sleep
fragmentation prior to the commencement of CPAP treatment [27].
us, it is possible that the results of our current study simply reect
the rebound phenomenon. Despite this contention, it should be
noted that improvements in sleep quality in the absence of CPAP or
MADs in patients diagnosed with OSA have never been reported in
the literature to the best of our knowledge. erefore, our preliminary
results might represent an alternative to CPAP and MADs for the
resolution of OSA.
It is known that patients report various degrees of compliance
with CPAP and MADs. Almeida et al. [28] assessed patients’
preferences regarding treatment with either CPAP or MADs for
OSA. e parameters assessed included: expectations and benets of
treatment, side eects, and other factors impacting treatment choice.
Patient expectations included: improved overall health and sleep,
elimination of OSA/reduced snoring, and reduced daytime fatigue.
Subject Pre-treatment
AHI
Post-treatment
AHI Treatment time (months)
A 5.4 3.1 16
B 18.9 7.1 19
C 21 2.5 13
D13.7 1 7
E 8.2 3.7 4
F19.7 2.7 7
G5.7 2 4
H 5.1 5.4 4
I 21.3 12.8 4
Mean 13.2 4.5 8.7
Std. dev. 7.2 3.6 5.8
p value 0.021
Table 1: Summary of changes in the AHI after BOAT with no appliances in the
mouth during sleep when the post-treatment sleep study was undertaken.
Figure 2: Graph showing changes in the apnea-hypopnea index (AHI) for the
subjects included in this study.

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But, previous studies have shown that without continued MAD use,
the underlying etiology of OSA is typically neither addressed nor
corrected. For example, Gong et al. [29] investigated the length of
treatment, long-term ecacy and safety of MADs in the treatment of
OSA in Chinese subjects. About 15% had been treated for >10yrs. e
longest treatment time was >12yrs., with a median of approx. 6yrs.
Side eects were reported to be transient and included tooth soreness,
dry mouth, occlusal changes and excessive salivation. In the long term,
MAD therapy remained eective as long as the appliance was worn
in the mouth while sleeping. For example, the AHI remained elevated
at 25.5events/hr. without the appliance in the mouth aer approx.
6yrs. of continuous therapy (although it was reduced to 4.2 with the
appliance in the mouth while sleeping). In contrast, the results of our
present study support the contention that the upper airway can be
improved in adults to the extent that relatively short-term BOAT may
potentially be successful in reducing the AHI to within normal limits,
since no appliance was in the mouth when the post-treatment study
was performed. If so, BOAT might represent an alternative to CPAP
and MADs with the potential for maximum medical improvement in
cases of mild to moderate OSA in adults.
To understand our results more precisely, other biochemical
and polysomnographic data other than AHI ought to be included.
For example, although the complete pathogenesis of OSA is not
fully understood, the role of OSA in atherosclerosis development is
important. Indeed, Ciccone et al. [30] found an increased carotid
artery intima-media thickness in patients with long-standing
OSA, which predisposed them to a higher risk of atherosclerosis.
Similarly, Ciccone et al. [31] reported a correlation between intima-
media thickness and inammatory markers, such as C-reactive
protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α
and pentraxin (PTX)-3, in the plasma of patients with OSA. More
importantly perhaps, Brunetti et al. [32] demonstrated that OSA
can impair endothelial function and thus worsen cardiovascular risk
children. On the other hand, while CPAP therapy is able to improve
endothelial function in patients with OSA [33], the role of MADs
and BOAT on endothelial function and atherosclerosis remains
unknown. erefore, our current results need to be viewed with
some caution as BOAT is a technique-sensitive protocol for upper
airway correction. e lack of a control group is another limitation of
this study (although there are no studies in the literature comparing
patients with OSA on CPAP therapy with untreated controls). But
our initial results are encouraging despite the limited sample size
of this preliminary study, so BOAT may be a useful method of
managing a selection of adults diagnosed with OSA. Nevertheless,
long-term follow up is needed to conrm these initial ndings, as
well as assessments of craniofacial and upper airway modications to
determine the stability of the changes achieved.
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Citation: Singh GD, Grifn TM and Chandrashekhar R. Biomimetic Oral Appliance Therapy in Adults with Mild to
Moderate Obstructive Sleep Apnea. Austin J Sleep Disord. 2014;1(1): 5.
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