A Systematic Review of Oral Modifications Caused by the Prolonged Application of Continuous Positive Airway Pressure (CPAP) and Intraoral Appliances in Patients with Obstructive Sleep Apnea (OSA)

Objective Prolonged use of oral devices as a substitute for traditional treatments has been studied in relation to the dental and skeletal changes associated with obstructive sleep apnea syndrome (OSA), which is a sleep-breathing disorder. Materials and Methods A review of articles indexed in PubMed, Google Scholar, Cochrane Library, Scopus, Web of Sciences, and CINHAL databases in September 2022 based on MeSH-based keywords with “dental and skeletal” and “oral appliance” and “obstructive sleep apnea” was examined to ensure that the keywords alone or cross-linked, depending on which base of the searched data, were used. 16 articles out of 289 articles were included in the research, and 273 articles were excluded due to lack of study. Conclusions CPAP treatment has limited dental or skeletal effects in short-term or long-term use. OAs and MADs show significant dental changes with prolonged use. MAS and TSD are more effective in short-term goals than CPAP. OAs' increase may cause dental and skeletal changes. MPD shows notable cephalometric alterations.


Introduction
Obstructive sleep apnea (OSA) is a type of sleep disorder that affects breathing.It is characterized by repeated episodes during the night where the upper airway is either partially or completely blocked, causing reduced airflow (hypopnea) or temporary cessation of breathing (apnea).These events result in inadequate ventilation of the alveoli, leading to decreased oxygen levels [1,2].In details, OSA is a type of sleep disorder that disrupts breathing due to weakened pharyngeal muscles, leading to reduced or stopped airflow despite persistent attempts to breathe.Most people with OSA experience loud and repetitive snoring, followed by brief pauses in breathing, during which airflow decreases and the upper airway becomes obstructed by a buildup of air in the throat [3].
According to a systematic review, the average prevalence in the general adult population was between 6% and 17%, with an average of 49% in the advanced ages.Obese men and women also had a greater prevalence of OSA.The overall body of evidence proves that the prevalence of OSA increases with age, male sex, and a higher body-mass index [4].
A study in Hong Kong found that embryonic secondary palate was a significant risk factor for OSA [5].
One of the prevalent signs of this condition is the presence of excessive daytime sleepiness (EDS) and fatigue [6].Other symptoms of OSA include struggling to stay asleep, waking up too early in the morning, and having difficulty falling asleep [7].The occurrence of this condition is twice as common in men compared to women, and its symptoms tend to worsen with age [3] with a prevalence of up to 60% among individuals aged 60 years and older.Reported data indicates that the prevalence of this condition among men aged 65-69 is 90% [1].
The diagnosis of OSA was addressed by the American Academy of Sleep Medicine (AASM), which proposed two methods in their guidelines.The first method involved using parameters for polysomnography (PSG) symptoms and related methods, which were last updated in 2005.The second method included clinical guidelines for utilizing unattended portable monitors for diagnosing OSA in adult patients.A workgroup of content specialists was assigned by the academy to provide updated clinical practice guidelines (CPG) on this topic.The objectives of the CPG included consolidating and updating information from previous guidelines on OSA diagnosis, such as optimal conditions for conducting laboratory PSG or home sleep apnea tests (HSAT) [8].
In case left untreated, this condition can result in various health complications including cardiovascular diseases, brain diseases, hypertension, metabolic disorders, cognitive disorders, depression, memory loss, and, ultimately, mortality [9].There are several effective treatments for OSA, which may include weight loss and exercise, nasal obstruction removal, avoiding alcohol, positive airway pressure (PAP) therapy, using oral appliances that reposition the jaw forward, and modifying pharyngeal soft tissue or facial bone to enlarge the upper airway [6].
Early diagnosis of OSA is crucial as it can significantly reduce life expectancy and quality of life.Therefore, therapeutic methods, such as positive airway pressure (PAP) therapy, are commonly employed to effectively manage the condition [10].The use of this method, which involves nasal administration, is considered the gold standard in OSA management [11].In order to promote compliance with treatment, moisturizers are employed in this approach.Additionally, treatment adherence may be influenced by other factors such as age, disease severity, and obesity up to a BMI of 35.However, it has been observed that treatment dissatisfaction and discontinuation are more commonly reported among female patients and those with hypertension.Consequently, this trend may contribute to an increase in mortality rates [12].
To mitigate and lower the impact of these factors, patients may be advised to consider alternative methods.One such option is the use of an oral appliance as a treatment alternative.Oral appliances are known to have fewer side effects, higher tolerance levels, and greater patient satisfaction compared to the previously mentioned methods [13].CPAP masks can be nasal, oro-nasal, or fullface, because mainly nasal and oro-nasal appliances may have effect on the dentition [14].
When evaluating the two options, nasal continuous positive airway pressure (CPAP) is found to have higher adherence and greater reduction in disease severity compared to oral appliances.Warm moisturizing can help alleviate side effects associated with positive airway pressure (PAP).How-ever, oral appliances are preferred due to lower pain levels and, in some cases, dissatisfaction with symptom improvement in the alternative method [12].Research has indicated that patients tend to favor oral appliances over CPAP or other treatments due to the comfort they provide and the resulting improvement in their quality of life [15,16].
The mandibular repositioning appliance (MRA) is a widely used oral appliance that is primarily used to advance the mandible and reduce upper airway collapse in patients with obstructive sleep apnea (OSA).There is evidence that this method is effective in treating mild, moderate, and severe cases of sleep apnea.These custom-made appliances are designed to provide precise alignment and function as stabilizers, preventing unwanted movement due to teethrelated problems.It is worth noting that the movement of the tongue may not always synchronize with the mandible while using MRA [17,18].Despite having specific goals, these appliances are not a homogeneous group because they vary significantly in design and function.However, in all of these appliances, the tongue is impacted either directly through the advancement of its muscles or indirectly through the advancement of the mandible [19].
These appliances are commonly associated with temporomandibular joint pain, increased salivation, dry mouth, and toothaches.It is common for these side effects to subside with time, however [20].
Apart from reversible and short-term side effects, the use of oral appliances (OAs) may also result in irreversible side effects, such as mandibular protrusion leading to skeletal and dental changes.These changes can be assessed through various imaging techniques and measurements of the mean change [21].Typically, skeletal changes tend to manifest within 1-3 years, while dental changes may become noticeable after three years [22].Smith's research, which involved cephalometric analysis, examined also the skeletal, dental, and soft tissue changes resulting from the use of oral appliances (OAs).The findings indicated significant dental changes, including a reduction in overjet, overbite, retroclination of maxillary incisors, and tuberosity of mandibular incisors.However, no clinically significant skeletal changes were reported in relation to the use of OAs [23].
Given the discrepancies in findings from previous studies, this research is aimed at investigating the long-term effects of oral appliances for obstructive sleep apnea (OSA) on dental and skeletal changes.

Materials and Methods
The search strategy and selection procedures of this systematic review included the dental and skeletal changes that occurred due in the long run of oral appliances for OSA treatment.The search was carried out in June 2022 in English, disregarding the 2010 to 2022 time interval, to study published or in-publish articles.PubMed, Google Scholar, Cochrane Library, Scopus, and Web of Sciences databases were systematically studied.Then, a manual review was conducted regarding other articles and their reference.
The keywords were selected from the MeSH thesaurus to search the articles.Moreover, free keywords were used to 2 BioMed Research International search articles along with the MeSH keywords.The keywords used to search ("dental and skeletal") and ("oral appliance") and ("obstrructive sleep opnea") were examined via + or AND.Afterward, the research results were provided in a PRISMA chart (Figure 1).To make sure regarding the used keywords, they searched again as cross-links, taking into account which database was researched.Upon confirming the related information, in terms of title and content, a checklist was provided as a table to extract information, and the different properties of trials were recorded in them.To prevent bias, all stages of extraction and examination of references were carried out by two independent researchers.Figure 1 shows the process of investigating and including the articles.

Exclusion Criteria.
Studies that used other methods to control OSA.

Quality Assessment and Data Extraction.
Two authors examined the credibility and quality of the articles separately.In case of disagreement, they reached a conclusion via discussion and consulting a third author (corresponding author).In order to assess the quality of the articles, the Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 was utilized (updated June 2017).The tool is commonly used to assess the quality of clinical trial articles.
A key feature of this tool is that it can detect any type of bias, such as selection bias, performance bias, assessment bias, attrition bias, reporting bias, and other forms of bias.Data extracted from the trials includes the study ID (first author's name and the year), study plan, number of participants, inclusion criteria, intervention properties, measured outcomes, ethics approval, and financing.As shown in Table 1, the properties of the included studies are summarized, as is the judgment of the authors regarding the risk of bias in the studies.

Findings.
The first stage of the study involved collecting all 289 articles from the databases, among which 233 English cases were studied.Then, 200 were eliminated after checking the title due to being irrelevant and repetitive.The abstracts of articles were studied, and then, 55 other articles were eliminated due to being irrelevant.Then, 18 articles were eliminated since they were not a clinical trial or lack of access to their full texts.Finally, 16 remained and were included in the research.
The research of Minagi et al. investigated the factors predicting dental changes due to the long-term use of OAs in patients with OSA.Night PSG was used to measure the den-tal changes.For this purpose, 64 people with an average age of 57 7 ± 14 2, who had been treated for OSA for 4 3 ± 2 1 years, participated in this study.Items included in the study are as follows: (1) polysomnography-it was performed as a pretreatment baseline in a sleep laboratory in a sleep center (AHI 0.5 events per hour); (2) the patients that were instructed to use OA during sleep for more than 5 hours a night and more than 5 nights a week; (3) also the patients that were patients who used OA for at least 1 year.In their study, the researchers found that there was a significant reduction in overbite and overjet during the treatment period as well as an increase in the line connecting the lower incisors to the mandible.There was a correlation between this reduction in overjet and the duration, frequency, and progression of mandibular OAs [24].
Doff et al. assessed the probable changes in the face and skull morphology long-term exposure to the adjustable OAs in comparison to CPAP in patients with obstructive sleep apnea/hypopnea.A digital lateral cephalogram with a baseline to determine the cephalometric changes concerning skull and face morphology was performed to measure the probable changes.The OA used in this research was a Thornton adjustable positioner (Airway Management Inc., Dallas, TX, USA) [25].
Hamoda et al. studied the extent and advancement of dental and skeletal changes due to the long-term use.The measurement tools were demographic data and radiographic images.OAM was used by patients in this research [26].
Gong et al. investigated the effectiveness and safety of the long-term use of OAs in the treatment of OSAHS in accordance with the treatment duration.They used PSG, radiography, and questionnaires to examine the mental effects and side effects of OAs [27].
Alessandri-Bonetti et al. assessed the dental-skeletal changes caused by the long-term and consistent use of a mandibular advancement device (MAD) in patients with OSA.This research used a cephalometric measurement tool and a 3D model analysis once at the beginning and then within 1 1 ± 3 5 years, and its correlation with snoring and OSA under treatment by the Silensor device [28].
Tsuda et al. studied the skull changes in adults with OSA after using nCPAP.The measurement tools in this study were basic PSG and a lateral cephalometric radiograph (LCR) [29].
Fransson et al. studied the effect of the mandibular protruding device (MPD) in patients suffering from OSA and snoring.The measurement tool used in this study was onedimensional basic cephalometric radiography [30].
Venema et al. examined the changes in dental obstruction regarding the long-term use of MAD and CPAP.TAP measurement tools were included (Airway Management Inc., Dallas, Texas, USA).The MAD measurement tools were SomnoDent (Somnomed AG, Australia) [31].
According to Pliska et al., long-term treatment of the mandibular advancement splint (MAS) in patients with OSA causes a number of dental changes.Overbite, overjet, dental arch width, and the relationship between dental arches were measured using a Digital Caliper in this study [32].
Eid and Seif El-Din compared the obstruction changes due to dental side effects between the OA and CPAP that 3 BioMed Research International used to treat the OSA.This study used PSG to measure the changes [33].
Ang and Dreyer examined and compared dental changes caused by monoblock and double-block appliances; an Electronic Digital Caliper, with a 0.01 mm scale, was used in this research [34].
Heda was concerned with the periodontal changes due to the treatment of OAM for 4.5 or more years in people with OSA.Research tools were dental records and molds [35].
Kim et al. analyzed and determined the changes in the position of the dental and skeletal structures in the images of cone-beam computed tomography (CBCT).This research used Carestream CS9300 CBCT scans with a voxel size of 0.3 mm [36].
The dental and skeletal effects in patients with OSAHS were investigated also by Laborde et al., after wearing MAD and with regard to the appliance, i.e., hard or semihard.The cephalometric criteria on lateral cephalogram and radiographic photos before and a minimum of 6 months after the treatment were used as the measurement tool [37].
Fransson et al. measured and assessed the position and obstruction of teeth due to 10-year use of MPD at night in patients suffering from OSA or snoring.This study used alginate impressions of the jaw, as well as dental plasters made using an index obtained at an intercuspal position (IP) [38].
Alessandri-Bonetti et al. tried to identify the prevalence of temporomandibular disorders (TMD) in untreated OSA patients.They compared the results to healthy individuals in terms of sex and age [39].

Results
A total of 1258 case studies were studied, and the results are outlined in Table 1.For patients with OSA, MAS and TSD treatments seem to be more qualified than CPAP treatment in short treatment.Long-term use of an oral appliance

Incomplete outcome data (attrition bias) Low risk
All the prespecified outcomes in the method section were addressed adequately Selective reporting (reporting bias) Low risk All the prespecified outcomes in the method section were addressed adequately

Other biases
The research was partly supported by the Capital Characteristics of Clinical Application Fund (D101100050010019).Ethics approval has been obtained.
Alessandri-Bonetti et al. [28] Methods Study design: retrospectively study Trial location: Italy Participants Number of participants: 20 participants Eligibility criteria: MAD therapy for more than 2 years without treatment discontinuation during the whole study period, MAD use for a minimum of 5 nights per week and usually for the entire night (assessed through a questionnaire administered at the long-term follow-up day), and availability of good quality study models and lateral cephalograms at the baseline and follow-up visits Intervention Participants had mild, moderate, and severe snoring that lasted an average of 3 5 ± 1 1 years.

Outcome
Primary outcome: the maxilla revealed a significant decrease in horizontal position and a significant retroclination of the upper incisor, while the mandible displayed a significant downward rotation and a proclination of the lower incisor Secondary outcome: decrease in upper total space discrepancy, overjet, and overbite.In the regression analysis, treatment time influenced the lower incisor inclination and OJ; participants' initial characteristics had an effect on OJ.

Notes
Ethics approval: This study was approved by the Institutional Review Board (N.268/15) 7 BioMed Research International

Intervention
Both baseline and follow-up cephalometry radiographs were obtained from 46 Japanese subjects who used nCPAP for at least two years.These two radiographs were analyzed, and changes in the craniofacial structures were assessed.

Outcome
Primary result: Cephalometric variables after nCPAP use showed significant anterior maxilla retrusion, decreased maxillary to mandibular discrepancy, supramental and chin position setback, maxillary incisor retroclination, and decreased facial convexity.Secondary result: No significant correlations were observed between craniofacial alterations, demographic characteristics, or nCPAP duration and no self-reported permanent changes in occlusion and facial profile

Notes
Ethics approval: The study protocol was approved by the local Kirigaoka Tsuda Hospital review board

Risk of bias
Bias resulted in small but significant (dental) changes rather than CPAP.
A significant decrease and change were observed in overbite and overjet, as the results of MASs (included 77 patients) and MPDs (included 77 patients).
In oral appliance and CPAP treatment, no changes in skeletal variables were found, while in prolonged OAM use and MAD treatment, negligible and insignificant skeletal changes were found.
Overall, the studies suggested that long-term use of OAs, CPAP, and MADs can result in remarkable dental changes, while skeletal changes may vary and may not be significant in some cases.Treatment duration and patient characteristics were identified as potential predictors of the observed changes.

Discussion
The present review found that CPAP treatment did not yield considerable dental or skeletal changes, as reported in studies involving both short-term and long-term use of CPAP.In contrast, long-term uses of OAs and MADs were associated with remarkable dental changes, suggesting that prolonged use of these treatments (without considering the age of participants) may be necessary to achieve optimal results in terms of dental changes.The effectiveness of treatments for OSA has been a subject of extensive research, with various modalities being explored.In particular, MAS, TSD, and CPAP have emerged as popular and efficient options for managing OSA.Patient characteristics, such as age, severity of OSA, and underlying skeletal structure, were also found to potentially influence the effectiveness of the treatments [40].Long-term OA therapy may cause dental movement and skeletal changes, leading to a reduction in overjet and overbite.These mechanical side effects are caused by the reciprocal forces applied to the teeth and jaw by the OA device.In the future, patients may experience aesthetic concerns or difficulties with chewing and biting due to these changes [41].One significant finding from the research is that MAS and TSD treatments appear to be more effective than CPAP in achieving short-term treatment goals [42,43].Although CPAP can effectively reduce the severity of OSA, a higher number of patients are choosing OA, as it has been shown to yield superior results in severe cases, particularly with adjustable OA [44].Treatment with OAs in OSA may lead to a significant increase of the upper airway volume with a subsequent decrease of AHI [43].MAS and TSD treatments have been shown to result in small but meaningful dental changes, as evidenced by observed decreases and changes in overbite and overjet.MAS and TSD treatments showed small but substantial dental changes compared to CPAP.However, in the MAS group, overbite and overjet were considerably reduced [44].For the OA and CPAP, despite their similarities in clinical practice, OA The method section's predetermined outcomes were all suitably addressed.

Selective reporting (reporting bias) Low risk
The method section's predetermined outcomes were all suitably addressed.

Other biases
There has been no funding given for this investigation.The ethics board has given approval.A conflict of interest will not matter.
15 BioMed Research International may not be able to completely eliminate all obstructive events during sleep, unlike CPAP [45].Individuals with MPD demonstrated notable alterations in all cephalometric measurements, with the exception of maxillary protrusion.Significant changes, including reduced overjet and overbite, were observed in the MPD group [30].We had some limitations.The patient characteristics such as age, severity of OSA, and underlying skeletal structure may influence treatment outcomes.Also, we did not find out the exact time period in all articles because some participants passed away before finishing the period of scheduled treatment.Controlling for these variables may be challenging.Dental and skeletal changes can be difficult to measure objectively, particularly over a long period of time.Considering measurement techniques needs reliable and valid documentation, particularly on long-term data included in the analysis.Mandibular advancement devices (MAD), tongue repositioning devices, rapid maxillary expansion (RME), and multiple other appliances are cases of OA treatment.Much further investigation on MAD is necessary since this category type of technology, MAD, is already broad and may include numerous such as twin-block appliances and Herbst appliances.On this topic, it would be wise to keep adults and children asunder so that more reviews are required.
To draw firm conclusions and examine how patient skeletal structure may influence treatment outcomes, additional studies evaluating gnathological parameters of patients with apnea using an advancement device and well-designed studies are required.Additionally, it should be considered that OSAS can promote enamel demineralization and periodontal problems [2].Therefore, future research perspectives could include the evaluation of fluoride [46], casein phosphopeptide-amorphous calcium phosphate [47], biomimetic hydroxyapatite [48], and other remineralizing agents in patients with OSAS.Finally, also the use of lysates [49], probiotics [50], or other natural compounds [51] that can have an influence on oral microbiota has to be tested in patients with OSAS in order to help in the maintenance of periodontal health.

Conclusion
CPAP treatment has limited dental or skeletal effects in short-term or long-term use.OAs and MADs show significant dental changes with prolonged use.MAS and TSD are more effective in short-term goals than CPAP.Longterm utilization of OAs, CPAP, and MADs can result in exceptional dental changes, whereas skeletal changes may change and may not be noteworthy in a few cases.In MAS treatment users, overbite and overjet were significantly decreased.

2. 1 . 1 .
Types of Studies.A clinical trial with parallel groups enjoying full texts in English was included in the study.2.1.2.Types of Participants.The various types of participants were as follows: individuals with long-term use of oral appliances for OSA or CPAP.2.1.3.Types of Interventions.Clinical trial interventions were used to examine oral appliances used to control OSA.

Table 1 :
Properties of the included studies.
Participants Number of participants: 62 participants, average age at start of treatment: 49 ± 8 6 years Eligibility criteria: adults with mild to severe wheezing or OSA.At least 8 years have passed since treatment Intervention Subjects had been receiving OAM therapy for at least 8 years Outcome Primary outcome: that there are significant and progressive dental changes with prolonged OAM use.Over the same time period, skeletal or postural changes were negligible.

Table 1 :
Continued.High risk Supplementary material is available at the European Journal of Orthodontics online.