Multivariate analysis of oral mucosal ulcers during orthodontic treatment

Abstract

BACKGROUND

Orthodontic treatment can easily cause local soft tissue reactions in the oral cavity of patients under mechanical stress, leading to oral mucosal ulcers and affecting their quality of life. At present, only limited literature has explored the factors leading to oral ulcers in orthodontic treatment, and these research results are still controversial.

AIM

To investigate the current status and related factors of oral mucosal ulcers during orthodontic treatment, aiming to provide a valuable reference for preventing this disease in clinical practice.

METHODS

A total of 587 patients who underwent orthodontic treatment at the Peking University School of Stomatology and Hospital of Stomatology between 2020 and 2022 were selected and allocated to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic therapy. A questionnaire survey was constructed to collect patient data, including basic information, lifestyle and eating habits, treatment details, mental factors, and trace element levels, and a comparative analysis of this data was performed between the two groups.

RESULTS

A logistic regression model with oral ulcers as the dependent variable was established. The regression results showed that age (≥ 60 years: odds ratio [OR]: 6.820; 95% confidence interval [CI]: 2.226–20.893), smoking history (smoking: OR: 4.434; 95%CI: 2.527–7.782), toothbrush hardness (hard: OR: 2.804; 95%CI: 1.746–4.505), dietary temperature (hot diet: OR: 1.399; 95%CI: 1.220–1.722), treatment course (> 1 year: OR: 3.830; 95%CI: 2.203–6.659), and tooth brushing frequency (> 1 time per day: OR: 0.228; 95%CI: 0.138–0.377) were independent factors for oral mucosal ulcers (P < 0.05). Furthermore, Zn level (OR: 0.945; 95%CI: 0.927–0.964) was a protective factor against oral ulcers, while the SAS (OR: 1.284; 95%CI: 1.197–1.378) and SDS (OR: 1.322; 95%CI: 1.231–1.419) scores were risk factors.

CONCLUSION

Age ≥ 60 years, smoking history, hard toothbrush, hot diet, treatment course for > 1 year, tooth brushing frequency of ≤ 1 time per day, and mental anxiety are independent risk factors for oral mucosal ulcers. Therefore, these factors should receive clinical attention and be incorporated into the development and optimization of preventive strategies for reducing oral ulcer incidence.

Key Words: Orthodontic treatment; Oral ulcers; Multivariate; Logistic regression; Prevent disease

Core Tip: Currently, there is limited literature exploring the factors leading to oral ulcers during orthodontic treatment, with considerable controversy. Therefore, this study uses retrospective data to explore and analyze the current situation and related factors of oral mucosal ulcers during orthodontic treatment in our hospital, providing a reference for the clinical prevention of this disease.

INTRODUCTION

Orthodontic treatment traditionally refers to the correction of teeth and the removal of malocclusion and deformed teeth, with the diagnosis and treatment procedures primarily involving determining the etiology and mechanism of the malocclusion to achieve an aesthetic modification of the affected teeth. Although this treatment can effectively ameliorate dental and skeletal problems, utilizing orthodontic appliances to adjust the coordination between facial bones, teeth, nerves, and muscles in the maxillofacial region can easily cause the reaction of the local soft tissues in the patient's oral cavity following mechanical stress and ultimately result in the accumulation of oral bacteria[1]. In the initial treatment stage, oral mucosal ulcers can sometimes occur due to the contact of the mucosa with orthodontic brackets[2-4]. Oral mucosal ulcers are a prevalent adverse reaction in patients undergoing orthodontic treatment, often presenting on the surface of the mouth and tongue margin and triggering a burning sensation and pain (Figure 1). Thus, the speech and diet of the patients are affected to a certain degree by these ulcers, which generally heal spontaneously within 1–2 week. However, oral mucosal ulcers tend to occur as repeated attacks, with some patients experiencing multiple infections over a short period that affect their quality of life. Currently, only limited literature has explored the factors leading to oral ulcers during orthodontic treatment, and those study results remain debated. Therefore, this study utilized retrospective data to investigate the current status and factors linked to oral mucosal ulcers during orthodontic treatment in our hospital, aiming to provide a reliable reference for improving the clinical prevention of this disease.

Figure 1 Schematic diagram of oral ulcers. A: Tongue mucosa; B and C: Oral-retropharyngeal approach; D: Gingiva.

MATERIALS AND METHODS

A total of 587 patients who underwent orthodontic treatment at the Peking University School and Hospital of Stomatology between January 2020 and January 2022 were enrolled and assigned to an observation or control group according to the incidence of oral mucosal ulcers during orthodontic treatment. The relevant data of the patients in the two groups were obtained using a pre-designed questionnaire survey.

Inclusion criteria

The patients were included if they met the following criteria: (1) Underwent orthodontics in our hospital; (2) Age of ≥ 18 years; and (3) No history of other dental diseases or abnormal dental morphology.

Exclusion criteria

The patients were excluded if they met any of the following criteria: (1) Severe systemic diseases (hypertension, diabetes, or cardiovascular diseases); (2) Communication difficulties that hindered the ability to independently complete the questionnaire; (3) Mental health disorders; or (4) Pregnant or breast-feeding women or other patients deemed not suitable to participate in this research.

All enrolled patients were informed of the research purpose, and signed informed consent was obtained from each patient.

Data collection

A unified questionnaire was administered to the included patients via telephone interviews to collect the following information: basic information (age, sex, and smoking and drinking history), lifestyle and eating habits (tooth brushing frequency, toothbrush hardness, dietary preference for meat, and dietary temperature), treatment details (treatment course, tooth position, disease type, and orthodontic appliance type), mental factors (anxiety and depression), and trace element levels (zinc, copper, and iron concentrations). Oral mucosal ulcers refer to persistent defects or destruction of the oral epithelium integrity, accompanied by surface necrosis and detachment that result in the formation of a depression. These ulcers can be classified as primary (recurrent aphthous ulcers) and secondary ulcers. The diagnostic criteria for oral mucosal ulcers were according to the criteria specified in the Diseases of Oral Mucosa, 4^th edition, People's Medical Publishing House[5]. Additionally, the recurrence of the symptoms in the patients with oral ulcers was recorded. Recurrence was defined as an increase in the area and number of ulcers (i.e. > 1 attack per month) that recurred 3 months following successful treatment.

The study data were entered by trained professionals using EpiData3.1 software via double entry of the collected data and verification of consistency. Finally, the data were logically reviewed and quality-controlled to ensure authenticity, accuracy, and reliability.

Research methods

Detection of trace elements: After obtaining consent from the patients, 20 μL of peripheral blood was collected from each patient by the senior chief doctor of our hospital. Subsequently, the quantitative measurement of the trace elements, such as zinc, copper, and iron, in the blood samples was conducted utilizing an atomic absorption spectrometer. Quantitative analysis of the trace elements by an atomic absorption spectrometer is based on the principle of light radiation absorption by gaseous atoms, with the wavelength of absorbed light corresponding to the specific emission spectrum of the stimulated atom. Based on this concept, the concentration of trace elements in patient serum was quantitatively determined according to the intensity of the absorbed radiation.

Anxiety and depression scores: The Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to assess the anxiety and depression levels of the patients. The two scales comprise 20 items each, and both scales have a 1–4 scoring system for rating the respondents’ feelings during the most recent week. The cumulative scores of each item are weighted to obtain the total SAS or SDS scores, with higher total scores suggesting greater levels of anxiety or depression, respectively. The current cut-off value for the standard deviation is 50 points, with scores of 50–59, 60–69, and > 69 indicating mild, moderate, and severe anxiety/depression, respectively.

Statistical analyses

All data were analyzed using SPSS 22.0 statistical software. Measurement data were expressed as mean ± standard deviation or median (interquartile range), while count data were presented as numbers (percentage). Furthermore, the measurement data were tested for normality. Normally distributed data were compared between groups via t-test, whereas the Wilcoxon rank sum test was employed for non-normally distributed data. Intergroup comparisons of count data were performed utilizing the χ² test. After conducting a univariate analysis with oral ulcer occurrence (with/without) as the dependent variable, variables with P < 0.1 were selected for subsequent modeling. A binary logistic regression model was then used to identify the independent risk factors for oral ulcers. Similarly, a binary logistic regression model with recurrence as a dependent variable was applied to detect the independent risk factors for oral ulcer recurrence.

The test level was set at α = 0.05 (two-tailed test), and P < 0.05 was considered statistically significant.

RESULTS

General patient information

As demonstrated in Table 1, the basic data of all 587 patients were analyzed after grouping them based on the incidence and recurrence of oral ulcers. Patients with oral ulcers had a mean age of 52.53 ± 11.10 years, and those without oral ulcers exhibited a mean age of 52.98 ± 11.94 years, with no significant difference in age between these two groups (P > 0.05). Among the patients who developed oral ulcers, 153 (26.06%) presented with recurrent symptoms. Except for drinking history, disease type, tooth position, and orthodontic appliance type, all other factors were significantly different between the two groups. Therefore, these factors were included in the models constructed for further comparison analyses.

Table 1 Comparison of the general data of the patients grouped according to the presence and recurrence of oral ulcers.

Categories	Indicators	Oral ulcer group, n = 297	Non-oral ulcer group, n = 290	P value	Recurrence group, n = 144	Non-recurrence group, n = 153	P value
Sex	Male	113 (38.05)	236 (81.38)	< 0.001	51 (35.42)	62 (40.52)	0.365
	Female	184 (61.95)	54 (18.62)		93 (64.58)	91 (59.48)
Smoking	No	178 (59.93)	258 (88.9)	< 0.001	93 (64.58)	85 (55.56)	0.113
	Yes	119 (40.07)	32 (11.03)		51 (35.42)	68 (44.44)
Drinking history	No	97 (32.66)	109 (37.59)	0.211	44 (30.56)	53 (34.64)	0.453
	Yes	200 (67.34)	181 (62.41)		100 (69.44)	100 (65.36)
Disease type	Dental caries	152 (51.18)	149 (51.38)	0.484	69 (47.92)	83 (54.25)	0.253
	Dentofacial deformity	72 (24.24)	60 (20.69)		41 (28.47)	31 (20.26)
	Periodontal disease	73 (24.58)	81 (27.93)		34 (23.61)	39 (25.49)
Toothbrush hardness	Soft	151 (50.84)	199 (68.62)	< 0.001	95 (65.97)	56 (36.60)	< 0.001
	Hard	146 (49.16)	91 (31.38)		49 (34.03)	97 (63.40)
Dietary preference for meat	No	218 (73.40)	243 (83.79)	0.002	108 (75.00)	110 (71.90)	0.545
	Yes	79 (26.60)	47 (16.21)		36 (25.00)	43 (28.10)
Dietary temperature	Warm	76 (25.59)	105 (36.21)	0.005	39 (27.08)	37 (24.18)	0.567
	Hot	221 (74.41)	185 (63.79)		105 (72.92)	116 (75.82)
Treatment course	≤ 1 year	84 (28.28)	157 (54.14)	< 0.001	47 (32.64)	37 (24.18)	0.106
	> 1 year	213 (71.72)	133 (45.86)		97 (67.36)	116 (75.82)
Tooth position	Non-anterior tooth region	158 (53.20)	136 (46.90)	0.127	89 (61.81)	69 (45.10)	0.004
	Anterior tooth region	139 (46.80)	154 (53.10)		55 (38.19)	84 (54.90)
Orthodontic appliance type	Straight-wire bracket	138 (46.46)	120 (41.38)	0.215	67 (46.53)	71 (46.41)	0.983
	Conventional straight wire	159 (53.54)	170 (58.62)		77 (53.47)	82 (53.59)
Age	< 60 years	179 (60.27%)	226 (77.93%)	< 0.001	95 (65.97)	84 (54.90)	0.051
	≥ 60 years	118 (39.73%)	64 (22.07%)		49 (34.03)	69 (45.10)
SAS score		44.66 (5.58)	37.31 (5.54)	< 0.001	44.69 (5.67)	44.64 (5.51)	0.940
SDS score		47.04 (7.51)	37.16 (5.15)	< 0.001	47.13 (7.12)	46.96 (7.88)	0.849
Zn		97.95 (20.53)	127.88 (26.83)	< 0.001	98.91 (21.36)	97.05 (19.74)	0.434
Cu		17.04 (6.40)	17.70 (6.03)	0.201	17.15 (6.48)	16.93 (6.35)	0.773
Fe		9.14 (1.50)	9.31 (1.52)	0.158	9.16 (1.49)	9.12 (1.51)	0.830

SAS: Self-Rating Anxiety Scale; SDS: Self-Rating Depression Scale. SAS and SDS scores and the trace element levels are presented as mean (standard deviation), whereas the remaining categories are expressed as the number of patients (percentage).

Multivariate analysis of factors associated with oral ulcers

Variables were assigned values as outlined in Table 2, and the independent variables with significant differences (P < 0.1) were included in the univariate analysis to establish the model with oral ulcers as the dependent variable. Age (60 years: odds ratio [OR]: 6.820; 95% confidence interval [CI]: 2.226–20.893), smoking history (smoking: OR: 4.434; 95%CI: 2.527–7.782), toothbrush hardness (hard: OR: 2.804; 95%CI: 1.746–4.505), dietary temperature (hot diet: OR: 1.399; 95%CI: 1.220–1.722), treatment course (> 1 year, OR: 3.830; 95%CI: 2.203–6.659), and tooth brushing frequency (> 1 time per day: OR: 0.228; 95%CI: 0.138–0.377) were found to be independent factors for oral mucosal ulcers (P < 0.05). Furthermore, the level of the trace element Zn (OR: 0.945; 95%CI: 0.927–0.964) was a protective factor against oral ulcers, while the SAS (OR: 1.284; 95%CI: 1.197–1.378) and SDS (OR: 1.322; 95%CI: 1.231–1.419) scores were demonstrated to be risk factors. Table 3 provides the complete details of the analysis.

Table 2 Assignment of values to the variables.

Variable	Assigned values
Sex	Male = 1; female = 2
Smoking history	No = 0; yes = 1
Drinking history	No = 0; yes = 1
Tooth brushing frequency	≤ 1 time per day = 0; > 1 time per day = 1
Toothbrush hardness	Soft = 0; hard = 1
Dietary preference for meat	No = 0; yes =1
Dietary temperature	Warm = 0; hot =1
Treatment course	≤ 1 year = 0; > 1 year = 1
Tooth position	Non-anterior tooth region = 0; anterior tooth region = 1
Disease type	Dental caries = 1; dentofacial deformity = 2; periodontal disease =3
Orthodontic appliance type	Straight-wire bracket = 1; conventional straight-wire = 2
Recurrence	Without = 0; with = 1

Table 3 Logistic regression analysis of factors associated with oral ulcers.

Parameters	Univariate model			Multivariate model
	OR	95%CI	P value	OR	95%CI	P value
Age
< 60 years	1.000			1.000
≥ 60 years	7.116	4.880–10.377	< 0.001	6.820	2.226–20.893	< 0.001
Smoking history
No	1.000			1.000
Yes	5.390	3.491–8.323	< 0.001	4.434	2.527–7.782	< 0.001
Toothbrush hardness
Soft	1.000			1.000
Hard	2.114	1.510–2.960	< 0.001	2.804	1.746–4.505	< 0.001
Dietary preference for meat
No	1.000			1.000
Yes	1.874	1.250–2.808	0.002	1.719	0.994–2.973	0.053
Dietary temperature
Warm	1.000			1.000
Hot	1.650	1.158–2.351	0.006	1.399	1.220–1.722	0.002
Treatment course
≤ 1 year	1.000			1.000
> 1 year	2.993	2.126–4.215	< 0.001	3.830	2.203–6.659	< 0.001
Sex
Male	1.000			1.000
Female	2.328	1.621–3.343	< 0.001	1.610	0.933–2.780	0.087
Tooth brushing frequency
≤ 1 time per day	1.000			1.000
> 1 time per day	0.309	0.218–0.437	< 0.001	0.228	0.138–0.377	< 0.001
Zn level	0.947	0.938–0.957	< 0.001	0.945	0.927–0.964	< 0.001
SAS score	1.262	1.213–1.314	< 0.001	1.284	1.197–1.378	< 0.001
SDS score	1.278	1.228–1.331	< 0.001	1.322	1.231–1.419	< 0.001

CI: Confidence interval; OR: Odds ratio; SAS: Self-Rating Anxiety Scale; SDS: Self-Rating Depression Scale.

Multivariate analysis of factors associated with recurrent oral ulcers

We further analyzed the recurrence of oral ulcers by modeling, with disease recurrence as the dependent variable and independent variables such as smoking history and tooth brushing frequency. The results showed that smoking history (smoking: OR: 3.588; 95%CI: 1.829–7.040), disease type (dentofacial deformity: OR: 0.396; 95%CI: 0.199–0.786), toothbrush hardness (hard: OR: 7.905; 95%CI: 4.044–15.451), dietary habits (non-dietary preference for meat: OR: 0.517; 95%CI: 0.263–0.984), disease location (anterior tooth region: OR: 2.319; 95%CI: 1.206–4.462), and tooth brushing frequency (≤ 1 time per day, OR: 2.894; 95%CI: 1.452–5.770) were independent factors for oral ulcer recurrence (P < 0.05). See Table 4 for further details.

Table 4 Logistic regression analysis of factors associated with oral ulcer recurrence.

Indicators	B	SE	Wald	P value	OR	95%CI
Smoking history	1.278	0.344	13.806	< 0.001	3.588	1.829–7.040
Tooth brushing frequency ≤ 1 time per day	1.063	0.352	9.111	0.003	2.894	1.452–5.770
Dentofacial deformity	−0.927	0.350	7.008	0.008	0.396	0.199–0.786
Hard toothbrush	2.067	0.342	36.555	< 0.001	7.905	4.044–15.451
Non-dietary preference for meat	−0.659	0.345	3.639	0.046	0.517	0.263–0.984
Disease in anterior tooth region	0.841	0.334	6.354	0.012	2.319	1.206–4.462

CI: Confidence interval; OR: Odds ratio.

DISCUSSION

Current status of oral ulcers during orthodontic treatment

In recent years, the proportion of people paying attention to the beauty and alignment of their teeth has been increasing due to the expanding and evolving social relationships and aesthetic needs[6]. Related research has shown that the number of individuals receiving orthodontic treatment in China has been growing at present, with an emerging trend in the younger population[7,8]. Although orthodontic treatment provides a good diagnostic effect and can improve facial beauty, it can also lead to numerous complications, such as enamel demineralization and oral mucosal ulcers, owing to the use of external appliances. Oral ulcers usually present within 2 week after commencing orthodontic treatment. At the initial treatment stage, the mucosa can become ulcerated following contact with orthodontic brackets. Ulcers may also appear during treatment because of the irritation at the end of the ligature or archwire. In this study, 153 patients (26.06%) experienced the symptoms of recurrent oral ulcers, similar to the recurrence rate of 22.24% (117 of 526 patients) in an investigation by Liu et al[9]. Oral ulcers are a multifactorial disease, with the risk factors varying across studies. Moreover, the research findings may exhibit deviations in populations from different regions and ethnicities. Therefore, this study explored the current status of oral ulcers during orthodontic treatment and the related factors in 587 patients, providing useful reference and evidence for the clinical prevention of this disease.

Multifactor analysis of factors associated with oral ulcers

According to this study results, age < 60 years, smoking history, hard toothbrush, hot diet, treatment course for > 1 year, and tooth brushing frequency of > 1 time per day were associated with oral ulcer occurrence. Additionally, Zn level (OR: 0.945; 95%CI: 0.927–0.964) served as a protective factor for oral ulcers, while the SAS (OR: 1.284; 95%CI: 1.197–1.378) and SDS (OR: 1.322; 95%CI: 1.231–1.419) scores were risk factors. Age ≥60 years was identified as an independent risk factor for oral ulcer development, potentially because older patients were more likely to develop oral mucosal ulcers and experience more severe symptoms than those who were younger due to the aging-related effects of decreased metabolism, poor oral mucosal adaptability, and reduced oral mucosal elasticity. Furthermore, most older people have systemic diseases, which in turn increase the possibility of oral ulcers to some extent. Furthermore, smoking habit has been shown to be a risk factor for intractable oral ulcers[10]. Toxic substances, including nicotine in cigarettes, can damage the oral mucosa, thereby diminishing the protective function of the mucosa and exacerbating the susceptibility of the oral cavity to bacterial or viral invasions and infections. The habit of smoking can also cause recurrent and intractable oral mucosal ulcers, consistent with our finding of smoking history as a risk factor for oral ulcer recurrence (OR: 3.588; 95%CI: 1.829–7.040). Moreover, the close relation between a hard toothbrush and oral ulcers may be attributed to the oral mucosal damage that can be easily caused by a hard toothbrush, ultimately leading to the occurrence and recurrence of oral ulcers[11].

Previous studies have also suggested that high dietary temperature is an independent risk factor for oral ulcers[12]. The consumption of food that is excessively hot or at a high temperature can lead to the destruction of oral mucosal cells. Such extremely hot dietary temperatures can result in the scalding of the oral mucosa and traumatic ulcer development, even in the absence of orthodontic treatment. A longer treatment course (i.e. > 1 year) and tooth brushing frequency of ≤ 1 time per day were also found to be risk factors for oral mucosal ulcers in this study. Good brushing habits are known to have a positive impact on oral cleanliness and bacterial elimination in the oral cavity. Conversely, an inadequate frequency of tooth brushing can lead to an unclean internal environment in the oral cavity that facilitates the proliferation of oral bacteria, thus escalating the likelihood of oral ulcers. Further, a dietary preference for meat can induce oral mucosal ulcers. In contrast, prior studies have suggested that vitamin B and trace elements in vegetables and fruits have therapeutic effects on oral ulcers[13]. The current study revealed that the trace element Zn had a protective role against oral mucosal ulcers, demonstrating a long-term healing effect on ulcers and inflammation. However, the relation between a dietary preference for meat and oral ulcers was significant only in the univariate analysis but not in the multivariate analysis, possibly due to the linear relationship with other variables, including trace elements. Therefore, future studies should control for other variables and employ larger sample sizes to comprehensively investigate the relationship between dietary preference for meat and oral ulcers.

Finally, the influence of mental factors on oral ulcers during orthodontic treatment was examined. Our results found that the SAS (OR: 1.284; 95%CI: 1.197–1.378) and SDS (OR: 1.322; 95%CI: 1.231–1.419) scores were risk factors for oral ulcers. Correspondingly, long-term anxiety and depression have been suggested to cause neurological dysfunction in patients[14,15]. A possible explanation for these observations may be that the increased nervousness during orthodontic treatment may activate sympathetic adrenal hormones and induce emotional tension, ultimately reducing patient immunity and causing oral ulcer disease.

Multivariate analysis of factors associated with oral ulcer recurrence

In addition to identifying the risk factors for oral ulcers, we further determined the factors linked to oral ulcer recurrence. Our analysis demonstrated that disease type (dentofacial deformity: OR: 0.396; 95%CI: 0.199–0.786) and disease location (anterior tooth region: OR: 2.319; 95%CI: 1.206–4.462) were associated with recurrent oral ulcers. Compared to the other disease types (i.e. dental caries and periodontal disease), dentofacial deformities were not prone to oral ulcer recurrence after orthodontic treatment. This result implied that dentofacial deformities have a specific protective effect against recurrent mouth ulcers. Considering that the anterior tooth region is an area of oral exposure and a frequently used area of the oral cavity, this region may be more prone to recurrent oral mucosal ulcers[16].

CONCLUSION

In summary, age ≥ 60 years, smoking history, hard toothbrush, hot diet, treatment course for > 1 year, tooth brushing frequency of ≤ 1 time per day, and mental anxiety are independent risk factors for oral mucosal ulcers during orthodontic treatment. Therefore, the incidence of oral ulcers during orthodontic treatment can be reduced by enhancing the protective measures for older patients. Moreover, efforts should be made to promote oral health-related knowledge and encourage patients to maintain good lifestyle habits after orthodontic treatment, including adopting a healthy diet with more vegetables and fruits, supplementing with trace elements and vitamins, employing correct tooth brushing methods, adjusting mentality, and alleviating anxiety and depression. All these strategies will contribute to improving immunity and preventing oral mucosal ulcers in patients during orthodontic treatment.