Poly (ADP-ribose) polymerase inhibitor LT-626: Sensitivity correlates with MRE11 mutations and synergizes with platinums and irinotecan in colorectal cancer cells

Journal of

Oral Rehabilitation

Journal of Oral Rehabilitation 2016 43; 443–450

Self-Reported bruxism and associated factors in Israeli adolescents A. EMODI PERLMANa*, F. LOBBEZOOa†, A. ZARb*, P. FRIEDMAN RUBIN*, M . K . A . V A N S E L M S † & E . W I N O C U R * *Department of Oral Rehabilitation, The Maurice and Gabriela Goldschleger School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel and †Department of Oral Kinesiology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute Amsterdam, Amsterdam, The Netherlands

SUMMARY Little is known about the epidemiological characteristics of sleep and awake bruxism (SB and AB) in adolescents. The aims of the study were: to assess the prevalence rates of self-reported SB and AB in Israeli adolescents; to determine the associations between SB/AB and several demographical, exogenous and psychosocial factors in Israeli adolescents; and to investigate the possible concordance between SB and AB. The study made use of a questionnaire. The study population included 1000 students from different high schools in the centre of Israel. Prevalence of self-reported SB and AB in the Israeli adolescents studied was 9
2% and 19
2%, respectively. No gender difference was found regarding the prevalence of SB and AB. Multiple variable regression analysis revealed that the following predicting variables were related to SB: temporomandibular joint sounds (P = 0
002) and feeling stressed (P = 0
001). The following predicting variables were related to AB: age (P = 0
018),

Introduction Bruxism is a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct circadian manifestations: it may occur during sleep (sleep bruxism, SB) or during wakefulness (awake bruxism, AB) (1). SB is characterised by a

Equal contribution. This study was undertaken in partial fulfilment of a DMD thesis at the School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel.

b

© 2016 John Wiley & Sons Ltd

temporomandibular joint sounds (P = 0
002), orofacial pain (P = 0
006), and feeling stressed (P = 0
002) or sad (P = 0
006). A significant association was found between SB and AB; that is, an individual reporting SB had a higher probability of reporting AB compared with an individual who did not report SB (odds ratio = 5
099). Chewing gum was the most common parafunction reported by adolescents. The results of this study demonstrate that self-reports of AB and SB are common in the Israeli adolescents population studied and are not related to gender. The significant correlation found between SB and AB may be a confounding bias that affects proper diagnosis of bruxism through selfreported questionnaires only. KEYWORDS: adolescents, awake, psychological factors, sleep bruxism, temporomandibular disorders Accepted for publication 4 February 2016

both a grinding type and a clenching type activity; AB is mainly characterised by a clenching type activity (2). Sleep bruxism is a centrally mediated condition of multifactorial aetiology (3). It may be classified as primary or secondary if there is a history of using certain medicines, drugs, alcohol or in case psychiatric disorders are involved (4,5). There is convincing evidence that SB is part of an arousal response and is related to disturbances in the central dopaminergic system (4,6). Based on clinicians or academics’ experience, it has been suggested that AB is associated with life stress doi: 10.1111/joor.12391

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A . E M O D I P E R L M A N et al. and anxiety caused by familial responsibilities or work pressure (7). Most evidence regarding the aetiology of bruxism, however, comes from studies that focused on SB (8–10). There is a wide variation in reported epidemiologic data for SB and AB (11). These various outcomes of prevalence rates are largely due to differences in the definition, diagnostic methods, population characteristics and research methodologies between these studies. Despite this widespread occurrence, all studies investigating the age pattern of sleep bruxism report a common trend for a prevalence decrease with age (12–14)]. According to a review article by Manfredini et al. (12), prevalence rates of SB among adults are between 9
3% and 15
3%, respectively, as defined as ‘3 times a week’, ‘frequent’ or ‘often’. Reports about the prevalence of SB in children appear to be less consistent than those in adults. According to a systematic review by the same authors on SB in children, the prevalence rates reported varied between 3
5 and 40
6% (8). A more complete picture of this age-related distribution will be achieved with the integration of epidemiological data in adults with those derived from epidemiological studies in children and adolescents. There is especially a clear need for more large-scale studies on this topic. A few years ago, a large-scale study was performed in the Netherlands on both SB and AB among adolescents [10]. Since then, no other large-scale (n ≥ 1,000) epidemiological studies have been performed on bruxism (SB and AB) in adolescents. For this reason, it was decided to conduct this study, using the same questionnaire as employed in the Netherlands (10), in a large sample of Israeli adolescents. The study’s aims were threefold: to assess the prevalence rates of self-reported SB and AB in Israeli adolescents; to determine the associations between SB/AB and several demographical, exogenous and psychosocial factors in Israeli adolescents; and to investigate the degree of association (concordance) between SB and AB in Israeli adolescents.

groups: a Jewish non-religious population, a Jewish religious population and an Arabic population.

Materials and methods

Predictor variables

Population One thousand students from different high schools in the centre of Israel participated. The cohort of students was composed of three different ethnic

Ensuring anonymity and consent The Chief Investigator of the Israeli Ministry of Education approved the study after ensuring its anonymity. The students received full explanations about the study’s aims and importance and were encouraged to ask questions. They were informed that they are free to refuse to participate in the study and that this will not affect their studies in the school in any way. They were also informed that the study is completely anonymous and that to ensure anonymity, and they were requested to place the completed questionnaire into an envelope and sealed it before returning it to the investigator. Only after all participants had all of their a priori questions answered and their consent was received, the questionnaires were handed over. Procedure. Each student answered his or her questionnaire alone but in the presence of the investigator (AZ). The participation rate was 100%, that is all students agreed to participate in the study. The questionnaire contained 20 multiple-choice questions and was based on the one used in an earlier study performed among Dutch adolescents. The Dutch team (10) already tested the reliability of the questionnaire, and the instrument was forward-translated from Dutch into Hebrew by a bilingual member of the team (AEP). Outcome variables Sleep bruxism in the past 3 months was assessed by the following question: ‘Have you been told, or did you notice yourself, that you grind your teeth or clench your jaws when you are asleep?’ (Yes, no, unknown). Awake bruxism in the past 3 months was confirmed via the following question: ‘Are you aware that during wakefulness you are clenching or grinding your teeth?’ (Yes, no, unknown).

The personal and demographic variables included age, gender and ethnic background. To determine the symptoms of oro-facial pain and/or functional disturbances of the masticatory system in the past month, the following questions were asked: © 2016 John Wiley & Sons Ltd

SELF-REPORTED BRUXISM IN ADOLESCENTS ‘Have you had pain in the face, jaw, temple, in front of the ear or in the ear?’ (No, yes); ‘Have you had pain in your neck?’ (No, yes); ‘When you wake up in the morning, do you experience pain or a tense feeling in your jaw?’ (No, yes); ‘Does your jaw make a clicking or popping sound when you open or close your mouth, or while chewing?’ (No, yes); and ‘Does your jaw make a scraping or grating sound when you open or close your mouth, or while chewing?’(No, yes). Each student’s psychological state in the past month was assessed by asking two questions: ‘Do you feel stressed?’ and ‘Are you feeling sad (“blue”)?’ (Never, from time to time, regularly, often, every day). Additional questions that were asked included the following: ‘Do you smoke cigarettes?’; ‘Do you drink alcohol?’ (Both questions: no, occasionally, regularly, often, very often); and ‘Are you wearing orthodontic braces right now, or have you had them?’ (No, yes) (10). Statistical analysis Prevalence data were stratified by gender and age, and ratios were calculated by dividing the number of persons with the condition of interest (i.e. SB or AB) by the total number of respondents within each age group. Single regression analyses were performed to determine the univariate associations between the various predictors and the respective outcome variable. To study which of the various predictive variables have the strongest relationship with sleep or AB, a multiple logistic regression model was built using the unstratified data set. Predictors that showed a significant association with the outcome variable (i.e. P-value < 0
10) were entered in the multiple regression analysis. Only, the variables with the highest association with the outcome variables were retained (P ≤ 0
05). Data were analysed using SPSS statistics version 21
0*.

Results In total, the sample consisted of 456 children from the Jewish non-religious population, 490 children from the Jewish religious population, and 54 children were of Arabic origin (total 1000). The age range of the cohort was 12–18 years (mean  SD age = 15
1  1
5 years).

*SPSS, Inc, Chicago, IL, USA © 2016 John Wiley & Sons Ltd

Neck pain was commonly reported (37
8%), while a low occurrence of mouth-opening difficulties and chewing difficulties was found (5
1% and 5
3%, respectively; Table 1). Prevalence rates of 20% and 5% for alcohol consumption and smoking, respectively, were found. Many students felt blue and stressed, but most participants reported experiencing these feelings only sometimes (Table 2). Prevalence rates The prevalence of SB in the participating boys was comparable to that in girls (10
6% versus 8
7%) with an overall prevalence of 9
2%. The prevalence rates of AB divided over the two genders were identical (19
2%). Association between SB and AB A statistically significant concordance (P < 0
001) between AB and SB was found. Participants who reported performing SB were five times more likely to Table 1. Descriptive statistics: oro-facial pain and masticatory functional symptoms Number of participants Oro-facial pain No 800 Yes 198 Neck pain No 620 Yes 376 Awakening with pain or stiffness Never 771 Sometimes 195 Regularly 4 Often 11 Very often 7 Difficulty opening one’s mouth No 934 Yes 50 Difficulty chewing No 932 Yes 52 Clicking joint sounds No 808 Yes 186 Joint sounds No 908 Yes 83 Orthodontics No 682 Yes 309

Prevalence (%)

81
2 19
8 62
2 37
8 78
4 19
4 0
40 1
1 0
7 94
9 5
1 94
7 5
3 81
3 18
7 91
6 8
4 68
8 31
2

445

446

A . E M O D I P E R L M A N et al. Table 2. Descriptive statistics: exogenous factors and mental state

Cigarette smoking Never Sometimes Regularly Often Very often Alcohol consumption Never Sometimes Regularly Often Very often Stress Never Sometimes Regularly Often Very often Feeling blue Never Sometimes Regularly Often Very often

Number of students

Prevalence

935 26 13 4 22

93
5 2
6 1
3 0
4 2
2

791 166 16 17 6

79
4 16
7 1
6 1
7 0
6

187 602 72 106 30

18
7 60
4 7
2 10
6 3
0

205 690 17 59 22

20
6 69
6 1
7 5
9 2
2

report AB than a participant who did not report SB (odds ratio = 5
10; 95% CI 3
10–8
40). Logistic regression analyses Multiple variable regression analysis indicated that a statistically significant correlation was found only between SB and joint sounds (P = 0
002) and between SB and feeling stressed (P < 0
001) (Table 3). In addition, statistically significant correlations were found between AB and age (P = 0
018), AB and orofacial pain (P = 0
006), AB and joint sounds (P = 0
001), AB and feeling stressed (P = 0
002) and AB and feeling blue (P = 0
006) (Table 4).

Discussion This study aimed to assess the prevalence rates of selfreported SB and AB in Israeli adolescents; to determine the associations between SB/AB and several demographical, exogenous and psychosocial factors in Israeli adolescents; and to investigate the degree of concordance between SB and AB. Before discussing

the results, we have to keep in mind that the diagnosis of bruxism was performed via questionnaires without any clinical examination or personal anamnesis, which represents the lower grade of diagnosis (‘possible’) of bruxism according to an international group of bruxism experts (1). To achieve the grade of definite diagnosis, the use of polysomnography (for SB) or electromyography for (AB) is needed. These techniques could not be employed because such an examination is not feasible in an epidemiological study on a large population of individuals. Awake bruxism is very difficult to diagnose by a questionnaire. The response choices were limited to ‘No’, Yes’ and ‘Unknown’, which may have introduced response bias. The relatively easiest response to interpret (‘No’) assumes that there is agreement on what clenching and grinding during wakefulness means among adolescents. A ‘Yes’ answer, however, is much less definite. For example, not only should an individual respond ‘Yes’ in case he or she clenches the teeth, the answer should be ‘Yes’ as well when straining the masticatory muscles during sports activities. Likewise, in case these activities occur only once in the 3-month period, the answer should still be ‘Yes’. Thus, a positive answer may provide false information, and definitely does not address the chronic, low-level behaviours that probably characterise AB. This should always be taken into consideration when reading articles that deal with self-reported AB. Another limitation that we found when trying to compare our results with previous studies was that it is impossible to accurately compare prevalence rates between studies. All studies on this topic use different questionnaires and methodologies. Consequently, the following comparisons between the present study and previous studies should to be cautiously considered, with the exception of the Dutch study in which the same questionnaire and methodology were employed (10). On the other hand, the strength of the present study design is its anonymous nature. Students filled out an anonymous questionnaire that they sealed in an envelope. As the questionnaire was anonymous and the students understood that the data were not available to any of their school members, all of the students agreed to participate in the study. The present study results demonstrate that the average prevalence rates of SB and AB were 9
2% and 19
2%, respectively. On the other hand, the prevalence rates of SB and AB among Dutch adoles© 2016 John Wiley & Sons Ltd

SELF-REPORTED BRUXISM IN ADOLESCENTS Table 3. Single and multiple logistic regression models for the prediction of sleep bruxism

Predictor variable

Single regression Number

Gender Male 195 Female 490 Age 12–15 405 16–18 243 School type Non-religious 331 Religious 325 Arabic 41 Awakening pain or stiffness No 561 Yes 125 Clicking joint sounds No 573 yes 120 Joint sounds No 641 Yes 51 Smoking No 653 yes 30 Alcohol No 544 Yes 145 Stress No 550 Yes 145 Feeling blue No 629 Yes 63

Multiple regression

P-value

OR

95% CI

N.S.

1 0
814

0
505–1
311

N.S.

1 1
195

0
751–1
901

N.S. N.S.

1 0
776 1
465

0
490–1
231 0
638–3
365

0
012

1 1
941

1
166–3
232

1
732

1
030–2
912

0
002

1 3
052

1
597–5
833

N.S.

1 1
648

0
655–4
148

N.S.

1 1
412

0
850–2
345

0
001

1 2
499

1
556–4
015

N.S.

1 1
867

0
968–3
589

P-to-Exit

P-value

OR

95% CI

1 0
002

2
913

1
503–5
646

1 0
001

2
270

1
381–3
731

0
13

0
42

N.S.

0
39

0
47

0
36

N.S., Not significant. The inclusion criterion of P < 0
1 to enter and p > 0
05 to exit. For each factor included in the single regression, the number of cases included in the analysis is shown. Associations are expressed as odds ratio (OR) and 95% confidence interval (CI). For each removed predictor variable, the P-to-Exit is reported. Categorical cases having an odds ratio with the value 1 are referred to as the reference group.

cents were 14
8% and 8
7%, respectively (10). This divergence between the present study and the one by Van Selms et al. (10) is small as compared to the variance reported in the reviews on this topic (8,12–14). In the present study, Israeli adolescents more frequently reported feeling regularly or often stressed than their Dutch counterparts (10). The reason for this discrepancy may be found in the fact that the Israeli society experiences more psychological pressure from continuous exposure to threats to its security and unresolved economic strain (15). Within a stressful context in which Israeli adolescents live, high © 2016 John Wiley & Sons Ltd

levels of psychological and physical symptoms are generally reported (16). The prevalence of SB in Israeli boys was equal to the prevalence in Israeli girls. The Dutch study, however, found that girls were more likely to report SB than boys (10). That study was consistent with another Israeli study that was performed with Israeli adolescents (15–18 years old) in which a higher prevalence of bruxism (SB and AB) was found in girls (25%) compared with boys (13%) (14). In other study, however, no gender differences were found (11).

447

448

A . E M O D I P E R L M A N et al. Table 4. Single and multiple logistic regression models for the prediction of awake bruxism Single regression Predictor variable Gender Male Female Age 12–15 16–18 School type Non- religious Religious Arabic Facial pain No Yes Clicking joint sounds No Yes Scraping joint sounds No Yes Smoking No yes Alcohol No Yes Stress No Yes Feeling blue No Yes

Number

P-value

Multiple regression

OR

95% CI

P-to-Exit

P-value

OR

95% CI

0
027

1
521

1
048–2
208

0
006

1 1
815

1
190–2
766

0
001

1 2
683

1
512–4
760

244 609

N.S.

1 1
042

0
726–1
495

0
949

515 290

0
088

1 1
362

0
964–1
925

393 419 52

N.S. N.S.

1 0
785 1
075

0
561–1
097 0
551–2
100

569 54

0
001

1 2
163

1
482–3
157

703 157

0
003

1 1
841

1
252–2
706

788 67

0
001

1 2
840

1
696–4
757

630 7

N.S.

1 0
821

0
355–1
901

538 44

N.S.

1 1
265

0
858–1
864

560 64

0
001

1 2
535

1
764–3
644

0
003

1
893

1
241–2
189

622 33

0
001

1 2
703

1
680–4
346

0
006

1 2
182

1
256–3
792

0
398

0
082

0
065

0
112

N.S., Not significant. The inclusion criterion of P < 0
1 to enter and p > 0
05 to exit. For each factor included in the single regression, the number of cases included in the analysis is shown. Associations are expressed as odds ratio (OR) and 95% confidence interval (CI). For each removed predictor variable, the P-to-Exit is reported. Categorical cases having an odds ratio with the value 1 are referred to as the reference group.

In the present study, we found a significant correlation between SB and feelings of stress. Likewise, AB was significantly correlated with feeling stressed and feeling sad. In the Dutch study, the same associations were found (10). It should be kept in mind that the present study design does not allow drawing conclusions as to cause-and-effect relations. Nevertheless, the connection between psychosocial factors and AB may be explained by the hypothesis that AB seems to be associated with psychological factors and psychopathological symptoms, as discussed in a systematic review (17).

The results of this study demonstrate an association between AB and pain in the oro-facial area. These findings are in accordance with the theory that masticatory muscle pain results from awake rather than sleep activity (18). On the other hand, muscle stiffness when waking up in the morning was associated with SB. Van Selms et al. (10), who found the same association, believed that stiff feeling/pain in the morning is caused by SB, while oro-facial pain is caused mostly by AB. The explanation, according to Lavigne & Pallas (18), is that most SB episodes during sleep are phasic and do not cause pain, while there © 2016 John Wiley & Sons Ltd

SELF-REPORTED BRUXISM IN ADOLESCENTS are only few tonic or sustained contractions that may cause pain. This is in contrast to clenching while awake, which is characterised by more sustained contractions and accordingly of a higher probability of reports of pain (18). Awake bruxism and SB were both found to be significantly correlated with temporomandibular joint sounds. This is in accordance with the Dutch study (10). The theory explaining this association states that the load on the joint while bruxing results in a reduction of the intra-articular space, thus causing the disc to be displaced in an anterior position (19). Moreover, remodelling changes may occur as the result of force applied by the parafunctional activities, which might cause joint noises as well (10). In this study, there was a high concordance between SB and AB, that is reporting SB increases the odds for reporting AB fivefold (and vice versa). This is in accordance with Winocur et al. (20) and Manfredini and Lobbezoo (17), who stated that although AB and SB seem to have a different pathogenesis, they are difficult to distinguish. Possibly, individuals perceive them as a single entity, which hampers a proper diagnosis through self-reporting questionnaires. This fact may be a confounding bias when trying to analyse the effect of SB and AB separately and should to be taken into consideration when reading an article in which both entities of bruxism were only graded as possible (1). Due to the fact that this is a questionnaire-based study, the above-mentioned discussion on mechanisms that focused on the associations between SB/AB and the subsequent conclusion should therefore be handled with caution.

Conclusion The results of this study demonstrate that selfreports of AB and SB are common in Israeli adolescents and do not differ between both genders. The common associations that SB and AB share are with psychological stress and temporomandibular joint sounds. The fact that most of the predictor variables are mainly associated with AB corroborates the hypothesis that AB may affect the masticatory system more than SB. A significant association was found between SB and AB, that is an individual reporting SB had a high likelihood of reporting AB compared with an individual who did not report SB. This fact may be a confounding bias that can affect © 2016 John Wiley & Sons Ltd

the proper diagnosis of bruxism through self-report questionnaires.

Acknowledgments The study was self-funded by the authors. In this manuscript, all authors have made a significant contribution to the findings and methods. All authors have approved the final draft of the manuscript. None of the authors had any financial support or relationships posing conflict of interest. The Chief Investigator of the Israeli Ministry of Education approved the study after ensuring its anonymity.

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