The face of Dental Sleep Medicine in the 21st century

Abstract It becomes increasingly clear that some sleep disorders have important diagnostic and/or management links to the dental domain, hence the emergence of the discipline ‘Dental Sleep Medicine’. In this review, the following topics are discussed: 1. the reciprocal associations between oro‐facial pain and sleep; 2. the associations between sleep bruxism and other sleep‐related disorders; 3. the role of the dentist in the assessment and management of sleep bruxism; and 4. the dental management of obstructive sleep apnoea. From these topics' descriptions, it becomes clear that the role of the dentist in the recognition and management of sleep‐related oro‐facial pain, sleep bruxism and obstructive sleep apnoea is large and important. Since many dental sleep disorders can have severe consequences for the individual's general health and well‐being, it is imperative that dentists are not only willing to take on that role, but are also able to do so. This requires more attention for Dental Sleep Medicine in the dental curricula worldwide, as well as better postgraduate training of dentists who are interested in specialising in this intriguing domain. This review contributes to increasing the dental researcher's, teacher's and care professional's insight into the discipline ‘Dental Sleep Medicine’ as it has taken shape in the 21st century, to the benefit of all patients suffering from dental sleep disorders.

to dentists were described, namely sleep-related oro-facial pain, oro-facial movement disorders, breathing disorders, oral moistening disorders and gastro-oesophageal reflux, all of which require the attention of dentists. 2 In the present review, which is based on a symposium entitled 'Wake-up call: Dental Sleep Medicine is here to stay!', held on June 20, 2019, during the IADR/AADR/CADR General Session & Exhibition, Vancouver, BC, Canada, the reciprocal associations between oro-facial pain and sleep will be discussed first. Subsequently, the associations between sleep bruxism and other sleep-related disorders will be discussed. Thereafter, the role of the dentist in the assessment and management of sleep bruxism will be explained, followed by an overview of the dental management of obstructive sleep apnoea, notably oral appliances. This article's ultimate goal is to increase the dental researcher's, teacher's and care professional's insight into the discipline 'Dental Sleep Medicine' as it has taken shape in the 21st century, to the benefit of all patients suffering from dental sleep disorders.

| ORO -FACIAL PAIN AND S LEEP
As to better understand the reciprocal associations between oro-facial pain and sleep, a basic understanding of sleep itself is mandatory.
Hence, below, the phenomenon 'sleep' will be briefly introduced first, followed by a description of the current insights into (oro-facial) pain and its interaction with sleep.

| Sleep
Sleep is a natural process that enables us to recover from our energy expenditure during wakefulness. It also contributes to mood maintenance, immune system recovery, brain and muscle regeneration, and memory consolidation. Sleep follows an approximately 24hour cycle under light and environmental cues. The sleep 'centre' is localised in the brainstem, with interplay from the suprachiasmatic nucleus and the thalamus. During sleep, the cortex is relatively quiet, except during specific phases of arousal that naturally occur every 20-40 seconds. These arousals are cyclic physiological phenomena that occur to preserve homoeostasis and survival. Arousals are characterised by 3-10 seconds increases in, amongst others: heart rate; autonomic nervous system, brain and muscle activities; and body temperature. Their main function is to preserve sleep stability or to trigger a full awakening that can be associated with a fight or flight survival reaction. 3

| Pain and sleep
Adult humans need to sleep between 7 and 9 hours to feel rested.
Lack of sleep can be associated with bad sleeping habits or health issues (eg anxiety, depression, persistent pain, cancer). Sleep is not an anaesthesia or a coma, but rather an active state that filters external inputs. Pain during sleep, like any sensory input such as sound, will trigger arousals and, when needed, full awakenings to assure body protection. 4 Interestingly, placebo analgesia also remains active during sleep as revealed by recent studies. 5,6 This all illustrates that pain influences sleep.
Reciprocally, sleep also influences pain. For example, it is recognised that 3-4 nights of experimental sleep deprivation may trigger mood alteration and can initiate diffuse pain complaints in healthy subjects. 7,8 More recent studies confirmed that some dysfunctional processing in nociception can result from sleep deprivation, which will alter the activity of brain structures that are related to pain processing or reward modulation, for example enhanced activity at the cortex and reduced activity at the striatum, insula and nucleus accumbens. 9,10

| Oro-facial pain and sleep
Unrefreshing sleep is reported in many patients suffering from widespread musculoskeletal pains. 11 About half of the oro-facial pain patients, including patients with temporomandibular (TM) pain, report poor sleep quality, which suggests that oro-facial pain negatively influences sleep quality. 12 Reciprocally, a recent major study, the Orofacial Pain Prospective Evaluation and Risk Assessment (OPPERA) study, revealed that sleep quality is changed months before the novel onset of TM pain, which suggests that impaired sleep may also yield oro-facial pain. 13 In addition, such pre-diagnostic changes in the trajectory of sleep quality support the fact that many patients with TM pain also present sleep disorders, such as insomnia, respiratory effort-related arousal or sleep. 14-16 Furthermore, TM pain patients also tend to present more mood alteration, such as depression symptomatology, or sleep and/or awake bruxism as compared to healthy controls. [17][18][19]

| Conclusion
Form the above, it can be gathered that sleep and oro-facial pain may indeed be associated in a bidirectional manner. This reciprocal association seems to be influenced by multiple biological and psychosocial factors, although the exact underlying mechanisms are still unknown. Dentists should be aware of this complex interplay, and, importantly, they should be able to deal with the related diagnostic and management issues. Suggested strategies for the management of the oro-facial pain and sleep interaction by dentists are shown in Table 1. Even though the level of evidence is still rather 'lean' for the suggested management approaches, applying them in everyday dental practice will promote the professional collaboration between dentists and medical doctors specialising in sleep medicine.

| SLEEP BRUXISM AND OTHER SLEEP-REL ATED DISORDER S 1
Sleep bruxism (SB) is a dental sleep disorder with which dentists are confronted regularly in their everyday practices. SB can be comorbid to many sleep-related disorders. [20][21][22] Insight into the underlying mechanism of these relationships may enable distinguishing between the primary and secondary forms of SB. In the absence of an underlying medical aetiology, SB is considered primary, or idiopathic, whereas secondary SB is associated with a medical condition. The distinction between these two forms is important, because their management may be distinct. In cases where the primary form of SB has harmful consequences, management of SB is often necessary. However, when SB is a comorbid condition of other sleep-related disorders, management of the associated medical conditions by an expert physician should be the first focus. It is to be expected that the management of the sleeprelated disorder may prevent or reduce SB and its consequences on dental and general health.

| Sleep bruxism and obstructive sleep apnoea
The prevalence of SB in adult obstructive sleep apnoea (OSA; for more details, see 'Obstructive sleep apnoea: the dentist's role') patients is much higher than in controls, namely 26% based on selfreport, 23 and ranges from 34% to 65% based on polysomnographic (PSG) data. 24,25 This may suggest that both phenomena are associated with each other. Recently, four hypothetical scenarios for a temporal relationship between SB and OSA were proposed 22  Apart from the four hypothetical scenarios, age may also be critical for the association. 26,27 On the one hand, the prevalence of SB self-reports shows a natural course of reduction over the life time span, while on the other hand, the prevalence of OSA increases with increasing age, which suggests that the two phenomena may be concomitant and are physiologically unrelated. As proposed previously and reiterated in the hypothesis paper, SB activity may also have a protective effect against OSA by protruding the mandible and subsequently improving airway patency. 22,28 Clearly, to deepen our insight into the putative association between SB and OSA, experimental and clinical studies for exploring the underlying pathophysiological mechanisms, large data bank studies for the assessment of risk factors, and longitudinal clinical studies for causality are required. 29

| Sleep bruxism and restless leg syndrome/ periodic leg movements in sleep
The four cardinal diagnostic features of restless leg syndrome (RLS) include the following: (a) an urge to move the limbs, which is usually associated with paraesthesias or dysaesthesias; (b) symptoms that start or become worse with rest; (c) at least partial relief of symptoms with physical activity; and (d) worsening of symptoms in the evening or at night. 30 In addition, the patient must note a symptom of concern, distress, sleep disturbance or some impairments related to the sensations. Frequently, RLS also has a primary motor symp- TA B L E 1 Suggested strategies for the management of the orofacial pain and sleep interaction by dentists 3,4,11,12 Assess whether comorbidities like bad life habits, mood alteration, bruxism or adverse oral habits are contributing to the oro-facial pain condition

| Sleep bruxism and insomnia
Insomnia is defined as a sleep complaint that occurs at least three times per week for at least 3 months and is associated with daytime impairment. 34 The prevalence of insomnia in the general population ranges from 4% to 48%, depending on the definition of insomnia used and the methods used for determining the condition. 35 According to recent studies, bruxers have more difficulties with initiating sleep, complain more about a disturbed sleep and tend to report more excessive daytime sleepiness than controls. 36,37 Further, some SB patients also report problems with maintenance of sleep. 37 In another study, a positive association between SB and insomnia symptoms was observed in the general population in Brazil, using a sample of 1042 individuals who answered questionnaires and underwent PSG for SB diagnosis. 38 Despite these consistent findings, more research is needed to definitely confirm such an association, to assess the effect of ageing on the association and to clarify its relevance in comorbid SB management.  39 Two studies have reported on the association between SB and RBD with concomitant PD. 20,40 In Finnish patients with PD, the prevalence of SB was lower than that of the general population (5% vs 8%, respectively) based on self-report. 40 On the other hand, in a F I G U R E 1 Example of a 1-min page of a polysomnographic recording, displaying, from top to bottom, two electro-encephalographic (EEG) leads, an airflow channel, an oxygen saturation channel and four electromyographic (EMG) leads of the masseter and anterior temporalis muscles from both sides. Clearly visible are the following events: arousal in both EEG leads, hypopnea event in the airflow channel, oxygen desaturation in the oxygen saturation channel and rhythmic masticatory muscle activity in the EMG leads. In this example, the onset of the breathing event precedes the onset of the sleep bruxism (ie rhythmic masticatory muscle activity; RMMA) event [Colour figure can be viewed at wileyonlinelibrary.com]

| Sleep bruxism and REM sleep behaviour disorder
Canadian PSG study, it was found that both in patients with RBD only and in patients with concomitant RBD and PD, the rhythmic masticatory muscle activity (RMMA) index was significantly higher than in a control group. 20 In addition, in patients with RBD, the oromandibular myoclonus index was significantly higher than in the control group. The authors therefore suggested that in the presence of a tooth tapping complaint and a high frequency of RMMA during REM sleep, RBD may be suspected and further neurological assessment is recommended. 20 Future longitudinal studies monitoring RBD patient groups on the occurrence of SB and PD can further deepen our understanding of these conditions' correlations and may facilitate identifying the early presentation of PD or other neurodegenerative disorders.

| Sleep bruxism and sleep-related gastrooesophageal reflux disease
Sleep-related gastro-oesophageal reflux disease (GERD) is characterised by regurgitation of stomach contents into the oesophagus during sleep. Shortness of breath and/or heartburn can result, but occasionally the disorder is asymptomatic ('silent reflux'). Experimental and clinical evidence from studies done in Japan supports that SB and sleep-related GERD can be associated, at least in some cases. 41,42 In an experimental study, in which polysomnography, audio-video recording and oesophageal pH monitoring in 12 healthy adult males were performed, it was shown that intra-oesophageal acidification induces SB. 42 In another small sample size (n = 10) clinical study, the authors concluded that nocturnal bruxism may be secondary to nocturnal gastro-oesophageal reflux, occurring via sleep arousal and occurring with swallowing. 41 In short, the above-described evidence suggests that SB is associated with GERD.

| Conclusion
Although the evidence on the relation between SB and other sleep-

| SLEEP BRUXISM: THE DENTIS T ' S ROLE
The management of the primary and secondary forms of SB is one of the most challenging and debated topics in dentistry and sleep medicine. This section will first focus on the management of primary SB, followed by a description of the challenges of assessing and managing secondary forms of SB.

| Primary sleep bruxism
Over the years, several management strategies have been proposed for clinically controlling primary SB activity. 43

| Secondary sleep bruxism
As has been discussed in the previous section, SB has been re-

| Conclusion
Dentists will frequently be encountered with patients with secondary SB and comorbid sleep disorders. Screening for sleep complaints and symptoms is one way to improve chairside assessment: it will give an impression of clinical phenotypes and will be helpful to understand the patients' oro-facial symptoms and complaints related to personalised management (

| OBS TRUC TIVE SLEEP APNOE A : THE DENTIS T ' S ROLE
OSA is a key condition for dentists specialising in Dental Sleep Medicine. Below, OSA will be introduced in more detail, after which the role of dentists with various professional backgrounds in OSA is described from a North American point of view. OSA is a common disease, and its prevalence increases with age and weight gain. According to a comprehensive epidemiological study, 61 OSA prevalence between the ages of 50 and 70 years old is 36% and 61% for overweigh and obese men, respectively. The prevalence in women also follows increase in weigh, but is about a third of the prevalence found in men. From this, the high burden of OSA in the adult population can be gathered, as well as the necessity of treatment for a large percentage of the population.

| Oral appliances
Dental Sleep Medicine has taken its largest step with the intro- being more effective reducing the apnoea-hypopnea index (AHI), in general a much lower acceptance and adherence of CPAP was shown. 63 Importantly, studies comparing cardio-metabolic and subjective outcomes have shown no differences between the two treatments. 64

| Dentist's role in obstructive sleep apnoea
As since the mid 1990s dentists started seeing more and more patients with sleep apnoea, it was obvious that dentistry had a larger role other than only providing OA treatment. There are various aspects where dentistry can contribute to the field of sleep medicine, especially in OSA. An overview of the focus and role of various dental specialists in the assessment and management of OSA is provided in Table 3.
As a starting point, craniofacial development has for long been a field of research in orthodontics and paediatric dentistry. It is known that many syndromes that affect growth and development have an underdevelopment of the maxilla and/or mandible in common, which is highly associated with OSA. 65 Also, children with micrognathia or midface hypoplasia are at higher risk of OSA. 66 This is an important area for further development, as for now, skeletal malocclusion has not been shown to be more prevalent in OSA children compared to children without sleep-disordered breathing. 67,68 In the field of oral and maxillofacial radiology (OMFR), dentists commonly prescribe panoramic and cephalometric radiographs and are able to identify calcification of the carotid artery, which is a common condition amongst OSA patients. 69 More recently, with the advance of 3D imaging, cone-beam CT has been used to evaluate the craniofacial complex in three dimensions and to assess the upper airway. 70,71 Dental anaesthesiology is linked to OSA, because OSA patients are often prone to increased risk of complications during deeper se- It is more complex than one may imagine at first glance, while highly rewarding when treatment success can be achieved. 83 Consequences of the treatment with oral appliances are bite changes, with a mesialisation of the lower dentition and distalisation of the upper dentition. 84,85 Unfortunately, despite some attempts, 86 the prevention of these side effects has not been possible and the management of the changes in the occlusion have to be continuous as we know the dental changes are small but will continue as long as patients continue OA treatment. Orthodontists, 87 prosthodontists, implantologists and general dentists have to work together, and also with speech therapists, to better follow the patients and find new approaches to prevent and/or manage dental side effects. Specialist on the temporomandibular complex has found an increase of side effects in the beginning of treatment but not at the long term, 88 and bite changes have been solely related to dental angulations. 89 Longer follow-up research is still required to understand possible predictors of side effects, possible decreased efficacy of OAs with age and management of adherence. 90  92,93 Together with the present paper, it is the authors' ambition that awareness will finally descend that in the 21st century there is more to Dental Sleep Medicine is a broad dental discipline.

| Conclusion
In this article, first the phenomenon 'sleep' was briefly introduced, after which the bidirectional associations between sleep and (oro-facial) pain were described. Thereafter, two of the most prevalent dental sleep disorders, namely SB and OSA, were outlined. For SB, the condition's associations with other sleep-related disorders were described, while the role of the dentist was sketched in the recognition and management of sleep-related oro-facial pain, SB, and OSA. Clearly, that role is large and important. Since many dental sleep disorders can have severe consequences for the individual's general health and well-being, it is imperative that dentists are not only willing to take on that role, but are also able to do so. This requires more attention for Dental Sleep Medicine in the dental curricula worldwide, as well as better postgraduate training of dentists who are interested in specialising in this intriguing domain. 94,95 The above information also shows that there are still considerable gaps in our knowledge on dental sleep disorders, on how these disorders are causally linked to each other as well as to other sleep disorders, and on which biological and psychosocial factors are involved in these associations. As a consequence of all this, more research is needed, which will ultimately be to the benefit of our patients.

CO N FLI C T O F I NTE R E S T
The authors declare that they received no funding for this study. The have also stated explicitly that there are no conflicts of interest in connection with this article.

AUTH O R CO NTR I B UTI O N S
All authors contributed substantially to the conception, drafting and critical revision of this work. All authors have approved the final version for publication and are fully accountable for all aspects of the work.

PE E R R E V I E W
The peer review history for this article is available at https://publo ns.com/publo n/10.1111/joor.13075.