INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Oral appliances (OA) that advance the mandible have become increasingly popular for treatment of the obstructive sleep apnea syndrome (OSA). This is because OA represent a valuable alternative for treatment of patients who are not able to tolerate the standard therapy for OSA, nocturnal application of continuous positive airway pressure (CPAP), due to side effects, chronically impaired nasal ventilation, or for psychological and other reasons. Furthermore, OA offer advantages over CPAP for frequent travelers, who prefer to avoid the inconvenience of encarrying voluminous equipment, and for residents of areas where electrical power is not available. In several randomized studies (1), including our own (4), OA have been shown to improve symptoms and objectively measured breathing and sleep disturbances in patients with OSA.

Although the effectiveness of OA therapy for selected OSA patients is promising, there have been concerns over potential side effects during long-term treatment. Minor discomfort such as excessive salivation and sore jaw or teeth appear to be quite common (1, 2, 5) but generally of a temporary nature and may improve over a few months during continued OA treatment (2). A cross-sectional study of patients treated over up to 5 yr by a mandibular advancement splint focused specifically on dental side effects. These occurred in 81% of 132 patients and led to discontinuation of treatment in 7.5% (6).

Although alterations in geometry of the teeth and the facial skeleton may cause dental and temporomandibular joint discomfort, difficulties with chewing, and other inconveniences that may limit long-term treatment with OA, effects of this therapy on dentofacial morphology have not been rigorously studied. Therefore, our purpose was to investigate potential adverse effects of OA including subjective complaints, as well as changes in findings derived from cephalographies and dental plaster models in patients on continuous OA therapy over at least 1 yr. This prospective study was carried out among participants of a randomized controlled trial (4) comparing effectiveness of an OSA-Herbst appliance as previously used by others (3, 7, 8), and an appliance developed at our center, the OSA-Monobloc (Figure 1).

View larger version (54K): [in this window] [in a new window]   Figure 1.   Two types of oral appliances were employed: the OSA-Monobloc (A) consisting of an upper and lower part kept together by stainless steel wire, and a two-piece appliance, the OSA-Herbst (B). The upper and lower parts of the latter are connected by lateral telescopic Herbst attachments that allow limited side-to-side and opening movements of the mandible. The two pieces are held together by elastics.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Patients

Patients were recruited among participants of an earlier study on treatment of obstructive sleep apnea by oral appliances (OA) (4) who were on continuous therapy for more than 12 mo. The diagnosis of OSA was based on a typical history, including complaints of excessive daytime sleepiness, habitual snoring, nocturnal apneas observed by the bed partner (if applicable), and a sleep study with an apnea/ hypopnea index of at least 5 h¹, or breathing patterns with signs of sleep-disruptive snoring (9, 10) combined with an elevated arousal index of > 20 h¹. The patients were treated by an OA because they had refused or did not tolerate nasal continuous positive airway pressure. Active dental or gingival disease was first treated, if necessary. Patients had to agree to regular use of the OA and to medical and dental follow-up examinations according to the protocol.

Twenty-two of the original series of 24 patients (4) gave written informed consent to participate in the study, which was approved by the hospital ethics committee. The remaining two patients could not be followed-up as one had moved without notice and the other did not show up for the proposed appointments.

Measurements and Protocol

Evaluation at baseline. A general medical history and a clinical internal medical and dental examination were performed. A German translation of the Sleep Disorders Questionnaire by Douglass and coworkers (11), the German version of the Epworth sleepiness scale (12), and part of the sleep symptom questionnaire described by Kump and coworkers (13) modified for our needs (details provided in the online data supplement) were administered. The diagnosis and severity of OSA were confirmed by polysomnography (14). Sleep stages and arousals were scored according to standard criteria (15, 16). An apnea/hypopnea was defined as a decrease in the sum signal of the calibrated respiratory inductive plethysmograph to  25% of baseline for more than 10 s (9). A snore was defined by an excursion in the microphone channel that exceeded baseline noise by more than 50% and that was periodic with respiration. The snoring index was defined as the number of snores per hour of sleep (17).

Lateral cephalometric radiographs were taken according to standard techniques (18) (Comet CFT 501 cephalograph, Schweizer, Zürich, Switzerland). The patient was standing with his head tightly fixed by a cephalostat, the Frankfurt horizontal plane being parallel to the floor, and the teeth in full occlusion.

Dental plaster models were manufactured based on alginate impressions of the upper and lower dental arches obtained by means of an impression spoon. A wax bite in full occlusion and a construction wax bite with the desired amount of protrusion and opening to be achieved by the OA were also obtained. The plaster models and wax bites served two purposes: they were essential for the construction of the OA, and at the same time provided documentation of dental geometry for subsequent comparisons.

In each patient, two types of OA were fitted: an OSA-Herbst and an OSA-Monobloc as described previously (4) (Figure 1). The protrusion was initially set at 75% of maximal protrusion and, if necessary, adjusted within 4 to 8 wk according to symptoms and comfort of the patient. In an individual, the protrusion (range 4.3 to 10.1 mm) and opening (range 8.7 to 16.8 mm) for long-term treatment was made identical for both OA. Patients were encouraged to get accustomed to both OA, but after an adaptation period of 1 mo, they were free to use the OA of their preference.

Evaluation after 3 to 12 mo of OA therapy (median of 3 mo). To evaluate effectiveness of OA therapy, patients were asked to use the OSA-Herbst, the OSA-Monobloc, and no OA, each for one of 3 successive weeks. The sequence was determined according to a randomization table. At the end of each week a polysomnography was performed, and the Epworth sleepiness scale and the modified sleep symptom questionnaire were administered. These measurements were performed as part of our earlier study (4).

Evaluation after 12 to 30 mo of OA therapy. A median of 14 mo (range 12 to 30 mo) after initiation of OA therapy, symptoms and side effects were again evaluated. The Epworth sleepiness scale score, the modified sleep symptoms questionnaire, and a detailed questionnaire on side effects were administered (questionnaires are posted in the online data supplement). A clinical dental examination, a lateral cephalography (as described above), wax bites, and plaster models were performed. Polysomnographies were not performed.

Data Analysis

Cephalographies. The lateral cephalograms were digitized (Umax Power Look II scanner, Düsseldorf, Germany) and further processed by specialized software (SigmaScan Pro, SPSS, Richmond, CA) using a personal computer equipped with a 21-inch monitor. Calibration of distances was performed by storing a millimeter scale with the images. The software allowed cursor-assisted tracking of anatomic landmarks for semiautomated calculation of distances and angles. The standard cephalographic variables illustrated in Figure 2 were obtained (18, 19). A detailed description is provided in the online data supplement.

View larger version (166K): [in this window] [in a new window]   Figure 2.   Lateral cephalogram with anatomic landmarks (dots labeled with letters), linear (lines labeled with letters), and angle measurements (arrows). Measured variables are explained in detail in the online data supplement. Their abbreviations are listed in Table 3.

View larger version (17K): [in this window] [in a new window]   Figure 3.   (A) Schematical drawing of the lateral (buccal) aspect of the first molars on the right side. The anteroposterior relationships of the first mandibular and maxillary molars (M1) were determined bilaterally according to the Angle classification system (20) based on plaster cast measurements. Articulation of the buccal groove of the mandibular M1 with the mesiobuccal cusp of the maxillary M1 (vertical arrows) was designated as class I, neutroclusion, and defined as 0 mm reference. Distal displacement of the mandibular M1 relative to the maxillary M1, that is, articulation of the buccal groove of the mandibular M1 posterior to the mesiobuccal cusp of the maxillary M1, was designated as class II, distoclusion, and quantified by positive values in millimeters (horizontal arrow). Mesial displacement of the mandibular M1 relative to the maxillary M1, that is, articulation of the buccal groove of the mandibular M1 anterior to the mesiobuccal cusp of the maxillary M1, was designated as class III, mesioclusion, and quantified by negative values in millimeters (horizontal arrow). (B) A schematical sagittal cross section through the first left upper and lower incisors illustrates measurements of overjet and overbite performed on dental plaster casts kept in full occlusion by an articulator. The overjet is the horizontal distance between the rim of the upper incisor and the labial surface of the lower incisor. Overbite was determined by marking the projection of the rim of the upper incisor onto the labial surface of the lower incisor with a pencil, and measuring the distance of this line to the rim of the lower incisor.

To minimize the noise related to intraobserver variability, each cephalogram was analyzed three times by the same investigator with an interval of at least 1 d in between measurements and without knowledge of the respective results. The mean differences among successive distance and angle measurements did not exceed 0.02 mm and 0.01 degrees, respectively, for all variables. The mean discrepancy (i.e., the difference among successive measurements without respect to the algebraic sign) did not exceed 0.72 mm and 1.28 degrees, respectively, for all variables. Analysis of cephalographic data was based on the mean value from the three measurements of each variable.

Plaster models. Models were placed into full occlusion to perform measurements by means of a precision ruler with a resolution of 0.1 mm. Overjet was defined as the horizontal distance between the mesial end of the rim of the first upper left incisor and the labial plane of the first lower left incisor (Figure 3). To measure the overbite, the projection of the mesial end of the rim of the first upper left incisor onto the labial plane of the first lower left incisor was marked as a line by a pencil, and the vertical distance between the line and the mesial end of the rim of the first lower left incisor recorded (Figure 3).

The anteroposterior relationships of the molars were determined bilaterally according to the Angle classification system (20) (Figure 3). Normal relation among the first upper and lower molars, that is, the buccal groove of the mandibular first molar articulates with the mesiobuccal cusp of the maxillary molar, was considered as neutral position (class I, neutroclusion), and 0 mm reference was assigned to this condition. Distal displacements of the mandibular first molar relative to the maxillary one, that is, the buccal groove of the mandibular first molar articulates posteriorly to the mesiobuccal cusp of the first maxillary molar (class II, distoclusion), were quantified by positive values in mm. Mesial displacements of the mandibular first molar relative to the maxillary one, that is, the buccal groove of the first mandibular molar articulates anteriorly to the mesiobuccal cusp of the first maxillary molar (class III, mesioclusion), were quantified as negative values (Figure 3).

The measurements on plaster models were performed twice. The mean differences among successive measurements did not exceed 0.06 mm for all variables. The mean discrepancy (i.e., the difference among successive measurements without respect to the algebraic sign) did not exceed 0.11 mm for all variables. Data analysis was based on the mean value from the two measurements of each variable.

Statistics. Normality of distribution was evaluated with the Kolmogorov-Smirnov statistic. Normally distributed data were summarized as means ± SE and nonnormally distributed data as medians and quartile ranges.

Comparisons of corresponding values at successive time points were performed by paired t tests, Wilcoxon matched pairs test, or analysis of variance (Friedman ANOVA), as appropriate (21). Correlations among subjective side effects, duration of therapy, and measurements derived from cephalographies or plaster models were expressed as Spearman R correlation coefficients. Expected versus observed frequencies were evaluated by the Fisher exact p statistic. A probability of < 0.05 was considered as significant.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Effects of OA Therapy on Symptoms and Polysomnographic Variables

At baseline evaluation the median age (and quartile range) of the 22 patients was 49.5 (44.0 to 58.0) yr and their body mass index was 26.3 (25.4 to 28.4) kg/m². They suffered from moderately severe excessive daytime sleepiness, impaired performance ability that interfered with daily activities, and sleep disturbances (Table 1). Polysomnographies confirmed an elevated apnea/hypopnea index, snoring, and sleep disturbances (Table 2).

At a median of 3 mo (range 3 to 12 mo) of OA therapy several of the subjective symptoms were significantly relieved (Table 1). Polysomnographies documented a significant decrease in the apnea/hypopnea index, snoring time, the snoring index, and the arousal index (Table 2). The relative duration of rapid eye movement (REM)-sleep and stages III/IV (slow-wave) sleep were unchanged. At this point in time, 14 patients preferred the OSA-Monobloc, one patient preferred the OSA-Herbst, and the other seven indicated no preference (Fisher exact p = 0.002 OSA-Monobloc versus OSA-Herbst).

At a median treatment duration of 14 mo (range 12 to 30 mo), the subjective benefit regarding hypersomnolence, interference with daily tasks, snoring frequency, and snoring loudness remained significant (Table 1), suggesting persistent effectiveness of OA over this time span. All patients stated they were generally satisfied with the effect of their OA and wished to continue the treatment. They stated they would use their preferred OA for at least 3 nights/wk (median 7 nights/wk, quartile range 6.5 to 7). We could not objectively verify treatment compliance but inspection of the preferred OA revealed signs of regular use in every patient. Sixteen patients preferred the OSA-Monobloc, five the OSA-Herbst, and one had no specific preference (Fishers exact p = 0.04 for a difference in preference among the two OA). Ten patients had changed their preferences, four from no preference to the OSA-Monobloc, three from no preference to the OSA-Herbst, two from the OSA-Monobloc to the OSA-Herbst, and one from the OSA-Herbst to no preference. Apparently, a certain preference did not preclude that the other type of OA was (at least sporadically) used as well. Reasons for preference of the OSA-Monobloc were its greater effectiveness in relieving symptoms, simpler handling, and easier cleaning. Body mass index (median 26.8 kg/m², quartile range 26.0-28.1 kg/m²) had not changed in comparison to baseline before treatment.

Subjective Side Effects

All of the 22 patients reported some side effects, but they were of minor intensity and did not lead to discontinuation of therapy. The most frequently mentioned side effects were dryness of mouth (n = 19), tooth discomfort or pain (n = 13), hypersalivation (n = 12), jaw pain (n = 9), stiffness or pain of masticatory muscles (n = 8), occlusal change of tooth position (n = 7), and loosening of teeth (n = 2) (Figure 4).

View larger version (24K): [in this window] [in a new window]   Figure 4.   The intensity of disturbance by the most commonly reported subjective side effects after 12 to 30 mo of continuous OA therapy is illustrated. The median and the quartile range of the intensities are represented by a vertical line and a box, and the 5th and 95th percentiles by whiskers. The number of patients complaining of any side effect (intensity greater than 0) is indicated. Intensity is rated as 0 = not at all, 1 = rarely and hardly disturbing, 2 = rare, but disturbing, 3 = often, but hardly disturbing, 4 = often and disturbing, and 5 = always, strongly disturbing. Details on the questionnaire on side effects are given in the Online Data Supplement.

Cephalometric and Plaster Cast Measurements

Results of the cephalographic evaluation at baseline and after 12 to 30 mo of treatment with the preferred OA are listed in Table 3. Changes in cephalographic variables over this time period were minor but significant for the mean decrease in the upper incisors to the maxillary plane angle (Figure 5), and the mean decrease in the sella to nasion to point B angle.

View larger version (23K): [in this window] [in a new window]   Figure 5.   Changes in overjet (A) and upper incisors to maxillary plane angle (B). Individual (dots connected with lines) and median values (horizontal lines) at baseline and after 12 to 30 mo of OA therapy are depicted.

At baseline before initiation of treatment, three patients had a relative position of the mandibular to the maxillary first molar of within 0.5 mm of the neutral position on both sides (Angle class I). Nine patients had a class II distoclusion bilaterally and one patient had a class III mesioclusion bilaterally. The other nine patients had differing classes on the left and right side of the dental arches. At 12 to 30 mo five patients (two more than at baseline) showed neutroclusion bilaterally (within 0.5 mm of the zero reference position). The prevalence of bilateral class II distoclusion was identical (nine patients). One patient remained class III bilaterally and another developed a class III mesioclusion bilaterally. Six patients had differing classes of occlusion on the left and the right side. A mesial movement of the lower to the upper first molar was found on the right side in eight patients (displacement by 0.2-1.3 mm) and on the left side in nine patients (displacement by 0.1-1.2 mm). The mean decrease in intermolar position was significant on both sides (Table 3). Furthermore, a significant decrease in overjet and overbite was noted (Table 3 and Figure 5).

Correlations among Subjective Side Effects, Dental-Skeletal Geometry, Duration of Treatment, and Type of Appliance

There were no significant correlations among presence and intensity of subjective side effects and objective changes in orthodontic variables derived from cephalographies or plaster models with the exception of the correlation between the subjective impression of teeth movement (i.e., change of bite) and the decrease in intermolar position on the right side (Spearman rank order correlation coefficient R = 0.59; p = 0.004). The changes in the sella to nasion to point B angle were significantly and negatively correlated with the duration of treatment (Spearman rank order correlation coefficient R = 0.54; p = 0.02). There was no significant correlation between amount of protrusion and subjective or objective side effects.

The prevalence of any subjective side effect with an intensity rating of at least three points or more ("often, but hardly disturbing," see side effects questionnaire in the online data supplement) was not significantly different among patients preferably using the OSA-Monobloc (10 of 16 patients) and patients preferring the OSA-Herbst (2 of 5) (Fisher exact p = 0.49).

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

We have investigated subjective side effects and orthodontic changes documented by means of cephalographies and dental plaster casts during treatment of obstructive sleep apnea with mandibular advancement devices over 12 to 30 mo. Minor side effects, such as mucosal dryness or hypersalivation, transient tooth or jaw pain, or masticatory muscle stiffness, were quite common and occurred in 36% to 86% of patients (Figure 4). However, according to the patients own judgments, the subjective benefits experienced from OA therapy outweighed these minor inconveniences by far and did not lead to discontinuation of treatment.

Analysis of cephalographies and plaster models indicated minor but significant decreases in the upper incisors to maxillary plane angle, the sella to nasion to point B angle, in overjet, in overbite, and a slight mesial (anterior) movement of the first mandibular molars (Table 3). These findings are consistent with expected consequences of forces acting on the upper and lower dental arches during protrusion of the mandible. Generally, the orthodontic changes we observed were small and associated with symptoms of minor intensity that lasted a few minutes after removal of the appliance in the morning only. Nevertheless, the significant correlation of the subjective impression of teeth movement and the decrease in intermolar position on the right side suggest that certain patients indeed perceive minimal changes of bite. The changes in the sella to nasion to point B angle were significantly (and negatively) correlated with the duration of treatment. This raises concerns that regular use of OA over periods exceeding the time span of 12 to 30 mo covered by our study may lead to progressive orthodontic alterations that potentially may impose a limitation to long-term OA therapy. In view of the substantial relief of sleep apnea symptoms experienced by the patients, we considered continuation of treatment justified. However, our data emphasize the need for long-term follow-up during treatment of sleep apnea with mandibular advancement devices to allow timely identification and intervention, if clinically relevant orthodontic or other side effects occur.

Our data also demonstrate that the OSA-Herbst and OSA-Monobloc are effective in improving sleep-related breathing disturbances and symptoms in patients with obstructive sleep apnea. The beneficial effects of the OA on excessive daytime sleepiness, interference with daily tasks, and perceived snoring were maintained for at least more than 1 yr (Table 1).

Previous studies on OA therapy for sleep apnea have concentrated on the beneficial effects of this treatment modality short term (less than 1 yr) consisting of improvements of excessive daytime sleepiness and other OSA symptoms as well as in significant reduction of sleep and breathing disturbances recorded during polysomnography (1, 22). Side effects were not analyzed in some reports (3, 22); in others subjective complaints were cited but no objective orthodontic examinations were performed (1, 2, 5, 23).

During 4 mo treatment by an anterior mandibular positioner (Snore-Guard) that covered only part of the dental arches, side effects included sore teeth, sore jaw muscles, and excessive salivation (1). The intensity of these effects was mild in 36%, moderate in 20%, and severe in 4% (one) of 25 patients (1). Similar results were obtained in another study by the same group using an adjustable appliance that provided full coverage of dental arches (2). In a recent investigation on the Thornton anterior positioner (TAP), an appliance that allows adjustments of protrusion by the patients themselves, the most common side effects were teeth or jaw discomfort occurring at least rarely in 83% and 81% of 121 patients, respectively (23). Use of a mandibular advancement splint (MAS) by 57 patients with sleep apnea was associated with dryness of mouth (21%), excessive salivation (19%), bruxism (9%), and gum irritation (7%). Mild jaw discomfort on waking was present during initiation of treatment in 37 (65%) of the 57 patients but persisted after a 3-wk adaptation period in only 12 (21%) of them (5).

Being anchored on the maxillary dental arch, the mandibular advancement devices transmit forces upon the mandible via the teeth. In addition, the processi articulares of the mandible are forced out of their natural resting position during overnight application of OA. The nature of side effects observed in the cited studies and in our investigation, including teeth, masticatory muscle and jaw discomfort, and difficulties chewing in the morning, can be explained by these mechanisms.

In a recent investigation, a questionnaire evaluation of side effects was supplemented by clinical dental examinations in 106 patients treated for snoring or sleep apnea with a mandibular advancement splint over up to more than 5 yr (6). In 15 patients (14%) a decrease in overjet by a median of 1 mm was detected. Our analysis of dental plaster casts and cephalographies confirms a decrease in overjet and extends these observations onto documentation of other orthodontic alterations, such as a decrease in overbite, a reduction in the upper incisors to maxillary plane angle, a reduction in the sella to nasion to point B (SNB) angle, and a tendency for mesial displacement of the mandibular molars (Table 3). As the variables reflecting anatomy of the facial skeleton were not significantly changed during the observation period (Table 3) apart from the SNB angle, the alterations induced by OA seem to be mainly limited to changes in position of the teeth.

Because the mandibular advancement splint (5, 6) and the OSA-Monobloc and OSA-Herbst employed at our center had qualitatively similar effects on changes in dental geometry, the latter do not seem to be specific to one type of appliance. Rather, they are inherent to the principle of treatment, that is, mandibular advancement, which is thought to be an essential mechanism by which the pharyngeal lumen is increased thereby preventing upper airway obstruction during sleep (24).

Conclusions

Minor subjective side effects from mandibular advancement devices used for treatment of snoring and sleep apnea are quite common, and may be associated with measurable changes in position of the teeth and of occlusion. Severe discomfort or damage to the teeth or temporomandibular joints that would have led to discontinuation of therapy did not occur in the current study. Nevertheless, close orthodontic monitoring in addition to internal-medical follow-up of patients treated with OA is advisable to prevent potentially serious complications and ensure efficacy of treatment. Despite some side effects, the OSA-Herbst and OSA-Monobloc were well tolerated and proved to be a valuable alternative for therapy of sleep apnea and snoring in patients who were not able to tolerate other therapeutic modalities, in particular continuous positive airway pressure. The improvement of sleep apnea symptoms provided by the OA was maintained over at least more than 1 yr.