1http://dx.doi.org/10.20396/bjos.v18i0.8657272 Volume 18 2019 e191679 Original Article 1 Department of Orthodontics, Centro Universitário Hermínio Ometto-UNIARARAS, Araras, São Paulo, Brazil. Corresponding author: William Custodio Av. Dr. Maximiliano Baruto, 500 - Jd. Universitário Araras, SP, BR. Zip Code: 13607-339 Phone: 55 19 38610472 e-mail: wcust@hotmail.com https://orcid.org/0000-0003-1416-1414 Received: June 07, 2019 Accepted: August 29, 2019 Comorbidity of TMD and malocclusion: impacts on quality of life, masticatory capacity and emotional features Beatriz Moraes D’Avilla1, Michelle Cristina Berbet Pimenta1, Vivian Fernades Furletti1, Mario Vedovello Filho1, Giovana Cherubini Venezian1, William Custodio1,* Aim: to evaluate the synergic impact of muscular TMD and malocclusion on quality of life, masticatory capacity and emotional features of young adults. Methods: this cross-sectional study comprised 4 groups (n= 15): G1, individuals without TMD or malocclusion; G2, with TMD and malocclusion; G3, with TMD and without malocclusion, and G4, without TMD and with malocclusion. Muscular TMD was diagnosed by RCD/TMD. Data included quality of life (OHIP-14), masticatory capacity test (X50), emotional stress (PSS-14), depression (MDI), pain intensity and salivary cortisol. Comparative statistical analysis included One-way ANOVA and Tukey post hoc test (X50, stress and cortisol) and GENMOD followed by Wald test (OHIP-14 and pain data). Fisher’s and Pearson’s association analysis were carried out. Results: Comorbidity of muscular TMD and malocclusion leads to significant lower masticatory capacity (p<0.05).  TMD groups independently of the occlusal condition had considerably lower OHIP-14 scores and higher stress levels (self-perceived and hormonal) (p<0.05). There was no statistically significant difference of emotional depression among groups. A significant positive correlation was observed among quality of life, stress and pain perception. Conclusion: muscular TMD in the overlap of malocclusion potentializes their negative effect on masticatory capacity. In addition, the hindering effect of the comorbidity is variable, however, TMD has a greater negative impact on quality of life and stress, whilst malocclusion on mastication. Keywords: Temporomandibular joint disorders. Mastication. Malocclusion. Quality of life. Stress, psychological. https://orcid.org/0000-0003-1416-1414 2 D’Avilla et al. Introduction Association of temporomandibular disorders (TMD) and occlusal characteristics is controversial and evidences, at present, does not support a cause-effect relationship between these highly prevalent conditions of the population1. In addition, comorbid occlusal disturbances and self-perceived psychological conditions make difficult to draw the real impact of TMD on patients’ quality of life and on the functional response of their masticatory system2. Structural variations in components of the masticatory system, such as muscular disturbances, have now been characterized as main etiological factors for TMD3. However, occlusal disturbances have been considered as triggers, perpetuating and even contributory factors for TMD4,5. This lack of concordance may be related with the individual capacity of the body for adaptation to occlusal discrepancies overlapped with the predisposition to chronic pain conditions1,6. The pain related to TMD may generate changes in the mandibular kinematics, increas- ing the number of occlusal interferences and consequently, changing the masticatory pattern6. Furthermore, this may lead to compensation of muscles and other asso- ciated structures for the purpose of bearing excessive functional loads however, in a cyclic manner, this adaptation may accentuate the pain, and if not treated, lead to important tissue damage. Masticatory function in individuals with TMD has been suggested to be limited because the functional response of the masticatory system is subject to a complex interaction between physical and emotional aspects. The number of occlusal contacts, dimension of the grinding area, sagittal and transverse changes in the teeth and bony bases modulate masticatory capacity7,8. In addition to the occlusal factor, malocclusion may correlate with a reduction in masticatory capacity by hindering the ability of the muscle to work9,10. Since malocclusion and TMD may lead to functional harm, self-perception of oral health may determine a decline in the quality of life9. However, the pain component of TMD and compromised esthetic appearance resulting from malocclusion are subjec- tive factors that may be influenced by the emotional state10. Therefore, the levels of stress and depression are capable of changing the self-perception of the impact of these conditions on quality of life11. Thus, in patients with TMD or occlusal discrepancies, we may recognize an poorer masticatory function with concomitant impairment of quality of life. However, the direction of a mutual influence remains obscure. Thus, the aim of this study was to evaluate the role of TMD, malocclusion and their interaction in quality of life, mastica- tory capacity, and emotional aspects. Materials and methods Experimental design and participants This double-blind cross-sectional study had a parallel-group design, in which four inde- pendent groups were evaluated. Malocclusion and muscular TMD were considered 3 D’Avilla et al. independent variables while the dependent variables were masticatory efficiency, qual- ity of life, self-perception of pain, emotional stress, depression and salivary cortisol level. The subjects entry order for the different experimental tests was randomized (simple randomization by lottery method). The participants were not informed about their diag- noses regarding muscular TMD and malocclusion till the end of the study. The investi- gator who performed the examination for muscular TMD diagnoses and malocclusion assessment was blinded regarding the study objectives The other investigator that car- ried out the experimental tests was blinded to the patient allocation group. This study was approved by the Research Ethics Committee of the University Center of the Hermí- nio Ometto Foundation - FHO under protocol number 1.329.422. All participants gave their informed consent prior to their inclusion in the study. The participants, 210 young adults with the same educational level, were recruited at a University Dental Clinic (Araras, Brazil). The exclusion criteria were: missing teeth, use of orthodontic appliance, periodontal disease, subjects taking antidepressant, anti-inflam- matory, analgesic medications or those with the potential to change salivary flow, sub- jects undergoing treatment for TMD, and those with a history of trauma or surgery in the region of the head and neck. A total of 60 participants (mean age = 25.3, s.d. = 5.1) met the criteria and were selected and allocated to four gender paired groups (n=15). Group I (control) comprised individuals who were asymptomatic for TMD and with clinically normal occlusion; Group II, subjects with TMD and malocclusion; Group III, made up of individuals with TMD and with clinically normal occlusion; and Group IV, asymptomatic for TMD and with malocclusion. To diagnose the presence of TMD, the RDC/TMD (Research Diagnostic Criteria for tTemporomandibular Disorders) was used12. Individu- als with muscular TMD (RDC/TMD Groups Ia and Ib) were included in the sample. Occlusion that was considered clinically normal was based on the Angle Class I dental relationship, with a positive horizontal overjet and vertical overlap of less than 3 mm, a normal transverse relationship and Class I molar and canine relationship, among others characteristics as described previously by Manfredini et al.13 (2016). Subjects that didn’t presented two or more of the stablished occlusal features were consid- ered with malocclusion. The sample size of 15 participants per group, provided a test power of over 80% to detect differences of 5 in IMC, 2 in OHIP, 8 in PSS-14, 3 in cor- tisol, 0.7 in masticatory efficiency (assessed by the particle median (X50)), and 10 in the self-perception of pain (as assessed using a visual analog scale (VAS)), between means of the groups, with a level of significance of 5%. Masticatory capacity The masticatory capacity was determined using the masticatory performance test (X50)14. Briefly, the participants were instructed to chew, in the habitual manner, a por- tion of 17 standardized cubes of a chewable test material (Optosil Plus, Heraeuz Kulzer, Hanau, Germany) (weight = 3.4 g; edges = 5.6 mm) in a total of 20 masticatory cycles. The produced particles were fractionated by a system of 10 sieves with meshes with openings that ranged between 5.6 mm and 0.5 mm, coupled to a vibratory table for 20 minutes. The amount accumulated in each sieve was weighed on an analytical balance with a precision of 0.0001 g (Mark, 2060, Bel Engineering, Milan, Italy). Masticatory per- formance was evaluated by calculating the median particle size (X50) by means of the 4 D’Avilla et al. Rosin-Rammler equation15. In the equation, X50 é is the opening in a hypothetical sieve through which 50% of the weight is capable of passing. Thus, the lowest mean values of the particles (X50) denote the highest masticatory performance. Self-evaluation scales The impact of oral health conditions on quality of life was evaluated by the validated Brazilian version of the Oral Health Impact Profile (OHIP-14) questionnaire. This self-applicable questionnaire consists of 14 questions about oral-health related prob- lems experienced over the past year, with answers based on a Likert-type scale of 0 (never), 1 (hardly ever), 2 (occasionally), 3 (almost always) and 4 (always). The sum scores of responses obtained may vary from 0 to 56 points, and the higher the score, the greater the negative impact on the quality of life16. The self-applicable questionnaire PSS-14 (Perceived Stress Scale) was used to determine the impact of the level of emotional stress perceived17. This is made up of 14 questions that must be answered by considering only the last month. The responses are as follows: 0 (never), 1 (hardly ever), 2 (occasionally), 3 (almost always) and 4 (always). To calculate the total score, answers to questions with a positive connotation (4, 5, 6, 7, 9, 10 e and 13) were inverted. The result of the sum of the instrument score varies from zero to 56. The higher the final score, the higher will be the level of emotional stress perceived. The level of depression was determined using the validated Brazilian version of the Major Depression Inventory (MDI) questionnaire18. This comprises 10 questions with reference to the past weeks. As a measurer of severity, the score of the MDI varies from 0 to 50, because each of the 10 items may receive a score ranging from 0 (never) to 5 points (all the time). Thus a score between 20 and 24 classifies the depression as light, from 25 to 29 as moderate, and over 30 points, as severe depression19. Self-perception of pain intensity, immediately before and after the masticatory perfor- mance test, was evaluated using a visual analogue scale (VAS)20. VAS score was deter- mined by using a 10-cm line presenting in one extremity the “no pain” anchor and in the other “worst pain imaginable”. The participant was asked to place a line perpendicular to the VAS line at the point that represents their pain intensity. The distance (mm) from the vertical line traced from the value zero (absence of pain) was considered the pain intensity present. All tests were conducted by the same examiner, who was trained for to apply the experimental instruments and collecting the data in a standardized manner. Salivary cortisol As a biomarker of self‐reported mental stress, the salivary cortisol level was deter- mined. Stimulated whole saliva was collected with the use of Salivette® (Sarstedt AG & Co, Nümbrecht, Germany). Salivary collections were carried out under the same sampling strategy respecting the avoidance of recent food intake, exposure to men- tal stressors and the circadian rhythms of glucocorticoid21. The samples were stored in accordance with the manufacturer’s specifications, and evaluated in a laboratory with ISO 9001 certification. The exam was performed after the Salivette tubes were centrifuged at 1000g to separate the saliva, and subsequently submitted to chemilu- minescence analysis. The results were expressed in nmol/L. 5 D’Avilla et al. Statistical analysis The mean PSS14 score, salivary cortisol and masticatory performance (X50) values were submitted to analysis of variance (one-way ANOVA), followed by the Tukey test. The cortisol data were transformed into log base 10. The OHIP data were analysed using generalized linear models (Genmod) and the pain intensity scores using gener- alized linear models for repeated measures, followed by the Wald test. The associa- tion of TMD and malocclusion with depression (MDI) was analysed using the Fisher Exact test. The Pearson correlation analysis was used to correlate the other variables. All analyses were performed using the SAS (SAS Institute Inc., Cary, NC, USA, Release 9.2, 2010) and R (R Core Team (R Foundation for Statistical Computing, Vienna, Austria) programs, with a level of significance of 5%. Results The comparisons between groups regarding body mass index (BMI), masticatory per- formance (X50), impact of oral health conditions on quality of life (OHIP-14), perceived level of emotional stress (PSS14) and salivary cortisol, are presented in Table 1. The sample did not differ with regard to BMI (p=0.1337). The worst masticatory perfor- mance (highest X50 score) was observed in the comorbidity group (G2) (p<0.05). The higher masticatory performance were showed by individuals without malocclusion (G1 and G3), independently of muscular TMD presence (p<0.05). Compared with the negative control group (G1), the impact of oral health conditions on quality of life (OHIP-14), self-perceived emotional stress (PSS14) and salivary cor- tisol level was significantly higher in individuals with TMD (G2 and G3), independently of the presence/absence of malocclusion (p<0.05). Individuals whose overlapped muscular TMD and malocclusion (G2) and those with muscular TMD without malocclusion (G3) showed higher mean values of self-per- ceived pain even before mastication (p<0.05). After the masticatory function muscu- lar TMD implies higher pain levels independently of occlusal condition (G2 and G3) (p<0.05) (Figure 1). Table 1. Groups comparisons for BMI, X50, OHIP-14, PSS14 and salivary cortisol. (mean ± SD) Group Condition BMI x50 OHIP -14 PSS14 Cortisol † TMD Malocclusion G1 absence absence 21.8 ± 2.6 a 2.71 ± 0.65 c 0.53 ± 1.3 c 16.27 ± 762 b 3,83 ± 2,72 c G2 present present 20.3 ± 4.4 a 6.09 ± 0.89 a 6.53 ± 5.9 a 26.13 ± 6.33 a 7,45 ± 4,93 ab G3 present absence 23.0 ± 3.5 a 3.22 ± 0.62 c 5.20 ± 4.0 ab 23.53 ± 5.07a 7,87 ± 3,52 a G4 absence present 23.4 ± 4.8 a 4.90 ± 0.30 b 2.07 ± 2.5 bc 21.00 ± 5.59 ab 4,35 ± 2,59 bc p-value 0.1337 ≤0.05 ≤0.05 ≤0.05 ≤0,05 Different lowercase letters in the columns indicate the statistical difference. †Salivary cortisol level in micrograms per deciliter (μG / dL). 6 D’Avilla et al. Figure 2 presents the distribution of frequency of the degree of depression (MDI) in the groups. There was no significant differences among groups (p=0.5686). The majority of the volunteers presented no depression. Table 2 shows the correlations between the variables. A significant moderately posi- tive correlation was observed (p<0.05) between the impact of oral health conditions and the quality of life, s stress (r=0.40), and self-perception of pain before (r=0.39) and after mastication (r=0.44). Self-perception of pain before mastication presented a significant positive correlation (p<0.05) with X50 (r=0.64); that is, the higher the pain level before mastication, the worse was the masticatory performance. In contrast, the median particle size arising from mastication was not correlated with pain after the test (p=0.8879). Figure 2. Relative frequency (%) of the degree of self-perception of depression (MDI) according to the different groups. Malocclusion absence Malocclusion presence TMD absence TMD presence Absence Mild Moderate Severe 0 20 40 60 80 100 Malocclusion absence Malocclusion presence Figure 1. Pain self-perception by visual analogue scale (VAS) in as a function of groups and time. Malocclusion absence Malocclusion presence TMD absence TMD presence Before mastication After mastication 70 60 50 40 30 20 10 0 Malocclusion absence Malocclusion presence Malocclusion absence Malocclusion presence TMD absence TMD presence Malocclusion absence Malocclusion presence 7 D’Avilla et al. Discussion In this study the different carried out tests provided a substantial amount of infor- mation to suggest the impairment in masticatory function and quality of life due to muscular TMD, malocclusion, pain and emotional stress. The masticatory perfor- mance can be considered as an important method for evaluating the functionality of the stomatognathic system and it is capable of measuring food comminution potential, by quantifying the particle size. Patients with malocclusion evaluated during food chewing, showed significant lower masticatory performance when compared to controls (G1 e G3). Similar results were obtained in previous studies, showing that malocclusion had a negative impact on masticatory capacity22,23. The literature shows that patients with malocclusion usually have less occlusal contacts and reductions in the occlusal functional areas of teeth during mastication24. Greater masticatory function impairment was observed in muscular TMD co-occurrence patients (G2) (Table1). Possibly, the limitation of masticatory performance aims to avoid the pain exacerbation, which could explain the lower food comminution rates in patients with muscular TMD. Patients with TMD (G2 and G3) presented higher levels of pain before and after mastication, irrespective of the presence or absence of malocclusion. However, the pain generated by mastication was not necessarily correlated with the particle size obtained. The pain of patients with TMD probably limited their masticatory perfor- mance, leading to compensatory mechanisms such as a larger number of cycles, slower rate of mastication and accessory muscle recruitment22-24,25. Therefore, despite the presence of pain during mastication in the groups with TMD, the pres- ence of malocclusion had a greater impact on masticatory capacity. It must also be remarked that static or dynamic occlusal characteristics were not associated with TMD pain conditions. Pain or the structural changes associated with TMD limit or even deviate mandibu- lar kinetics, and consequently affect the masticatory pattern4,6. However, it is import- ant to emphasize that masticatory capacity may not be affected, even in individuals with TMD. The authors suggest that compensatory mechanisms that lead to greater Table 2. Pearson correlation coefficient (p-value) among assessed variables Quality of life Emotional Stress Pain before mastication Pain after mastication Salivary Cortisol X50 BMI -0.04 (0.7340) -0.10 (0.4307) -0.10 (0.4470) -0.04 (0.7647) -0.05 (0.6844) -0.14 (0.2661) Quality of life - 0,40 (0.0014) 0.39 (0.0022) 0.44 (0.0004) 0.13 (0.3343) 0.22 (0.0964) Emotional Stress - - 0.31 (0.0145) 0.13 (0.3137) 0.13 (0.3309) 0.29 (0.0245) Pain before mastication - - - 0.24 (0.0701) 0.20 (0.1251) 0.64 (<0.001) Pain after mastication - - - - 0.12 (0.3646) 0.02 (0.8879) Salivary cortisol - - - - - 0.15 (0.2517) 8 D’Avilla et al. recruitment of other masticatory muscles, such as the temporal muscles, may com- pensate for debilities resulting from TMD11,26. Thus, the results demonstrated that the impact on the functional response only became relevant when associated with the presence of malocclusion. Although TMD had no impact on masticatory capacity, we observed a negative impact on to the oral health-related quality of life (OHIP-14). Pain, a common symptom of TMD is believed to be the main factor related to compromised social behaviour, and the emo- tional and psychological state of the individual12,27. The impact of the oral health condi- tion on quality of life was higher when TMD was associated with the presence of mal- occlusion. Nevertheless, malocclusion alone did not determine greater compromise of quality of life, corroborating the findings of other studies25,28. The behavioural variations of each individual and non-experience of a clinically adequate occlusion made it difficult to evaluate the real impact on to the quality of life due to malocclusion28,29. Studies have suggested that when malocclusion has an impact on quality of life, this is due to the aesthetic-emotional component, and not due to the functional impact25,28. Moreover, both quality of life and TMD may be modulated by emotional aspects such as stress. In the present study, individuals with TMD not only presented self-percep- tion about stress, but also had higher salivary cortisol levels, a biomarker of physio- logical stress, corroborating with previous studies30. Emotional stress may be associ- ated with muscle hyperactivity and overload of the stomatognathic system, causing inflammation in the retrodiscal tissues, muscle fatigue and muscular TMD. The results demonstrated no direct correlation between stress and pain. It can be due to the fact that individuals with chronic stress, even with pain, may present lower levels of sali- vary cortisol as a result of the reduction in hormone secretion by the adrenal gland31,32. In the present study, no statistical difference in self-perception of depression was observed. Besides depression has an influence on TMD11,33, the onset time of the TMD of the included volunteers may be responsible for the non-association. The limita- tions of the present study included lack in information regarding the time-onset and frequency of TMD related pain, the non-selection of participants at random from the population and the absence of other emotional variables such as anxiety that may be related to TMD. However, sample homogeneity regarding to gender, age and BMI avoided biases. Clinically, the results indicate that although malocclusion has more effect on masticatory capacity, this functional impairment has less influence on the quality of life. Thus, the impact on quality of life is probably not related to the reduction in masticatory function, but rather to the pain component of muscular TMD. 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