The effect of obesity on orofacial pain during early orthodontic treatment with fixed appliances: a prospective cohort study

The effect of obesity on orofacial pain during early orthodontic treatment with fixed appliances:... Summary Introduction We have investigated orofacial pain in a prospective cohort of obese and normal-weight subjects undergoing fixed-appliance orthodontic treatment. Methods Fifty-five subjects (27 males, 28 females) mean age 15.1 (1.6) years and mean body mass index 30.2 (3.5) in obese and 19.4 (2.2) kg/m2 in normal-weight groups were followed for 1 week after appliance placement. Primary outcome was maximum-pain measured using a 100-mm visual analogue scale. Secondary outcomes included mean pain and oral analgesic consumption. Results Mean maximum pain for the total sample was 73.7 (standard deviation 14.8; 95% confidence interval 69.8–77.7) mm with no significant differences among groups (P = 0.247). However, mean maximum pain was higher at all time-points for the obese group and significant at 72 hours (P = 0.034). Total analgesia consumed by the obese group was also significantly higher than normal weight (P = 0.041). Multivariable regression found the only significant predictor for mean pain was time. After adjusting for confounding, obesity was associated with higher (+4.47 mm) mean pain at each time-point (P = 0.018). A significant association existed between obesity and total analgesic consumption (univariable-analysis, P = 0.035; multivariable analysis, P = 0.023). After accounting for confounders, obese patients were associated with taking a higher quantity of oral analgesics. Conclusions We found a trend towards increased mean pain and an association with increased analgesic consumption in obese subjects during the first week following fixed-appliance placement. Introduction Obesity is a specific disease state characterized by chronic subclinical inflammation mediated through excess adipose accumulation and the concomitant production of systemic proinflammatory factors (1). There has been a steady rise in obesity associated with Western societies during the last few decades, which represents a major health care challenge because of the significant associations between obesity and multiple chronic diseases (2). A wide range of risk factors have been associated with obesity, particularly a sedentary lifestyle and the consumption of high-calorific food, with adverse lifestyle patterns often established from early childhood (3). Obesity in children and young adults has also been associated with poor mental health and psychosocial problems, including depression, anxiety, and low self-esteem. There is an established relationship between obesity and chronic musculoskeletal pain, which can also manifest from childhood; (4) and there are also suggestions that obesity can influence peripheral pain perception, being a contributory factor for increased pain thresholds (5–8). Orofacial pain is a common adverse effect of orthodontic treatment with fixed-appliances, particularly during the first few days after placement (9–16). Archwire progression during treatment often produces further episodes of pain, which can collectively affect eating and sleeping, and impact on day-to-day activities (9). A number of studies have investigated the effect of different fixed-appliance systems on orthodontic pain, but there is little evidence to suggest that any particular appliance combination is associated with less pain than any other (12, 13, 15, 17–20). However, orthodontic pain during the first week following the placement of fixed-appliances has been shown to have a consistent and reproducible profile, increasing during the first 24 to 72 hours and then reducing to baseline levels after a week, (12, 15, 16, 18) which, provides a useful experimental model to investigate orofacial pain experience in different subjects. The purpose of the present study was to investigate the effect of obesity on pain in subjects undertaking routine orthodontic treatment with fixed-appliances. Specifically, this prospective cohort study compared orthodontic pain experience during the first week of fixed-appliance therapy in two groups of children aged between 12 and 18 years and classified as normal weight and obese based upon body mass index (BMI). Materials and methods Study design This prospective cohort study compared the effects of obesity on orthodontic pain experience during initial tooth alignment with fixed-appliances. Ethical approval was obtained from the United Kingdom National Research Ethics Service (14/LO/0769) and written informed consent was received from all parents, guardians, and children. We report and present data according to the STROBE statement (21). Setting Participants were recruited from those attending for routine fixed-appliance orthodontic treatment in the Department of Orthodontics at King’s College London Dental Institute between January 2015 and June 2016. Follow up for this investigation covered the period from acquisition of baseline records and appliance placement up to the completion of tooth alignment (placement of a 0.019 × 0.025-inch stainless steel rectangular archwire in the lower arch). Data collection for this part of the investigation took place during the week immediately following placement of fixed orthodontic appliances for each participant. Participants Eligibility for inclusion in this study included patients with the following criteria: (1) 12 to 18 years old at the start of treatment; (2) no medical contraindications or the taking of regular medication (including antibiotic therapy in the previous 6 months); (3) in the permanent dentition, and (4) moderate-to-severe mandibular arch incisor irregularity (4–12 mm). Following informed consent, the body weight of subjects was measured to the nearest 0.1 kilogram (kg) using a calibrated scale and height was measured to the nearest centimetre (cm) using a wall-mounted rule. BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2). United Kingdom Royal College of Pediatrics and Child Health/World Health Organization growth charts were used to calculate and classify BMI centile in relation to age and sex (22). All measurements were taken by a single trained operator (HFS). Variables Subjects were classified as normal weight (BMI centile 2–91) and obese (BMI centile > 98). Those classified as underweight (BMI centile < 2) and overweight (BMI centile 91–98) were excluded from the study, respectively. Baseline tooth alignment prior to the start of treatment was calculated from a scanned dental stone cast using an irregularity-index, which measures the horizontal linear contact-point displacement of each mandibular incisor from the adjacent tooth and therefore represents the sum of the five individual displacements (23). Periodontal health was measured clinically using established validated gingival and plaque indices (24, 25). The bonding method and fixed-appliance protocol was standardized between groups (MBT prescription pre-coated 3M Victory 0.022-inch brackets, 3M Unitek, Monrovia, USA). After bracket bonding, a 0.014-inch nickel titanium archwire was tied in to the lower dental arch and ligated using conventional elastomerics. The archwire was cut distal to the first molar teeth and not cinched. No bite planes, auxiliary arches, intermaxillary elastics, headgears, or temporary anchorage devices were used during the period of investigation. All appliances were placed by postgraduate orthodontic trainees under the direct supervision of a consultant orthodontist. Patients were provided with a pain diary to complete over the week following placement of the fixed-appliance. The diary recorded orthodontic pain immediately after appliance placement (T0), at 4 hours (T1), 24-hours (T2), 72-hours (T3), and 1-week (T4) following the appointment by means of a 100 millimetre (mm) visual analogue scale (VAS) using the terms ‘Very comfortable’ and ‘Very uncomfortable’ as peripheral weightings (26). The VAS score is the distance from the left end of the line to the point of the subjects’ mark, measured to the nearest mm. Each VAS score was measured on two separate occasions by the same operator (HFS); with the mean of the two measurements taken as the representative value. In addition to the VAS score, subjects noted the consumption and dosage of oral analgesics during the period of observation. Each subject was free to take non-prescription oral analgesia as required. The pain diary was completed by the patient and returned at the following appointment. The primary outcome measure was maximum-pain experience during initial alignment with fixed orthodontic appliances, whilst secondary outcomes were (1) mean pain at each time-point, (2) use of analgesics, and (3) number of analgesics taken during this period of treatment. There were no changes to outcomes following study commencement. Pain diaries were coded appropriately so that both outcome assessor (HFS) and person responsible for the statistical analysis (SNP) were blinded to subject classification. Data coding was broken after the end of the analysis and no breach of blinding was identified. All VAS measurements were extracted in duplicate 2 weeks apart and agreement/reliability were assessed with the Bland–Altman limits of agreement (27) and the concordance correlation coefficient (28), respectively. Study size Study size calculation for this investigation was based upon the outcome of initial rate of orthodontic tooth alignment, which gave a required sample of 23 per group and has been described previously (29). A post hoc power analysis was performed to assess, if this study had sufficient sample to identify a set 30 per cent difference in maximum pain in obese compared to normal-weight patients. Baseline maximum pain (74.63 mm) and common standard deviation (SD) for both groups (21.95 mm) originated from a previous study in the same clinical setting (16), while alpha for the independent t-test was set at 5 per cent. The results of the power analysis indicated that the present study has 96 per cent power to identify the specified effect on the primary outcome of maximum-pain experience. Statistical methods Descriptive statistics were calculated to characterize the experimental groups, including means and SDs for continuous variables and frequencies for binary outcomes, after checking for normal distribution. Initial crude differences in baseline and outcome data were calculated with independent t-tests and chi-square tests. The effect of obesity on the primary outcome (maximum-pain experienced during alignment) and all secondary outcomes was investigated using univariable (crude) and multivariable generalized estimation equation regression models with robust standard errors, adjusted for the confounding effect of baseline data (sex, age, baseline-irregularity, baseline-pain), and co-interventions (previous tooth extraction and use of analgesia during alignment). Results are reported as unstandardized coefficients or odds ratios (ORs) for continuous and binary outcomes, respectively. In the analysis of mean pain across time-points, the model accounted for within-patient and time-point correlations. Analysis of residuals was conducted to confirm no violation of the linear regression assumptions. A post hoc subgroup analysis by gender was conducted, but is reported only briefly, due to the lack of statistical power. All analyses were carried out using Stata 12.0 (Statacorp, College Station, Texas, USA). A two-tailed P value of 0.05 was considered statistically significant with a 95% confidence interval (CI) for all tests. Results Participants This prospective cohort study included 55 patients (27 male and 28 female) with a mean age of 15.1 (SD, 1.6) years and mean irregularity index of 7.6 (SD 2.4; 95% CI 6.9–8.2) mm. No patient drop-outs existed during the study period and all distributed pain diaries were collected and analysed. Mean overall BMI of the cohort was 24.7 (SD 6.2) kg/m2. Table 1 shows baseline demographics and clinical characteristics of the two cohorts at start of treatment. The normal-weight group had a mean BMI of 19.4 (2.2) whilst the obese group had a mean BMI of 30.2 (3.5) kg/m2. Apart from BMI, there were no significant differences among groups for baseline characteristics. Table 1. Baseline demographics of subjects included in the study. SD, standard deviation; BMI, body mass index.   Overall  Control  Obese  P value  Patients  55  28  27    Male/female, n  27/28  15/13  12/15  0.50*  Age, mean (SD)  15.1 (1.7)  15.1 (1.6)  15.1 (1.9)  0.99#  Plaque index (SD)  0.56 (0.32)  0.57 (0.32)  0.54 (0.31)  0.75#  Gingival index (SD)  0.74 (0.39)  0.74 (0.40)  0.73 (0.38)  0.93#  Crowding, mean (SD)  7.6 (2.4)  7.0 (2.3)  8.2 (2.4)  0.06#  BMI, mean (SD)  24.7 (6.2)  19.4 (2.2)  30.2 (3.5)  <0.001#  Tooth extraction, n (%)  8 (15%)  4 (14%)  4 (15%)  0.96*    Overall  Control  Obese  P value  Patients  55  28  27    Male/female, n  27/28  15/13  12/15  0.50*  Age, mean (SD)  15.1 (1.7)  15.1 (1.6)  15.1 (1.9)  0.99#  Plaque index (SD)  0.56 (0.32)  0.57 (0.32)  0.54 (0.31)  0.75#  Gingival index (SD)  0.74 (0.39)  0.74 (0.40)  0.73 (0.38)  0.93#  Crowding, mean (SD)  7.6 (2.4)  7.0 (2.3)  8.2 (2.4)  0.06#  BMI, mean (SD)  24.7 (6.2)  19.4 (2.2)  30.2 (3.5)  <0.001#  Tooth extraction, n (%)  8 (15%)  4 (14%)  4 (15%)  0.96*  *P value from chi-square test. #P value from independent t-test. View Large Table 1. Baseline demographics of subjects included in the study. SD, standard deviation; BMI, body mass index.   Overall  Control  Obese  P value  Patients  55  28  27    Male/female, n  27/28  15/13  12/15  0.50*  Age, mean (SD)  15.1 (1.7)  15.1 (1.6)  15.1 (1.9)  0.99#  Plaque index (SD)  0.56 (0.32)  0.57 (0.32)  0.54 (0.31)  0.75#  Gingival index (SD)  0.74 (0.39)  0.74 (0.40)  0.73 (0.38)  0.93#  Crowding, mean (SD)  7.6 (2.4)  7.0 (2.3)  8.2 (2.4)  0.06#  BMI, mean (SD)  24.7 (6.2)  19.4 (2.2)  30.2 (3.5)  <0.001#  Tooth extraction, n (%)  8 (15%)  4 (14%)  4 (15%)  0.96*    Overall  Control  Obese  P value  Patients  55  28  27    Male/female, n  27/28  15/13  12/15  0.50*  Age, mean (SD)  15.1 (1.7)  15.1 (1.6)  15.1 (1.9)  0.99#  Plaque index (SD)  0.56 (0.32)  0.57 (0.32)  0.54 (0.31)  0.75#  Gingival index (SD)  0.74 (0.39)  0.74 (0.40)  0.73 (0.38)  0.93#  Crowding, mean (SD)  7.6 (2.4)  7.0 (2.3)  8.2 (2.4)  0.06#  BMI, mean (SD)  24.7 (6.2)  19.4 (2.2)  30.2 (3.5)  <0.001#  Tooth extraction, n (%)  8 (15%)  4 (14%)  4 (15%)  0.96*  *P value from chi-square test. #P value from independent t-test. View Large Primary outcome (maximum-pain intensity during alignment) Mean maximum-pain intensity across all time-points for the total sample was 73.7 mm (Figure 1; SD 14.8; 95% CI 69.8–77.7) with no significant differences among groups (Table 2; P = 0.247). Reported mean maximum pain was higher at all time-points for the obese group compared to control with a statistically significant difference at T3 (P = 0.034; Table 2). A greater percentage of the obese group reported taking oral analgesia when compared to control (74 versus 57 per cent), but this difference was not significant (P = 0.187). Figure 1. View largeDownload slide Box plot showing the predicted maximum pain during the whole alignment period (mm in VAS) from the multivariable regression analysis. VAS, visual analogue scale. Figure 1. View largeDownload slide Box plot showing the predicted maximum pain during the whole alignment period (mm in VAS) from the multivariable regression analysis. VAS, visual analogue scale. Table 2. Results on patient-reported mean maximum pain and use of oral analgesia. SD, standard deviation; VAS, visual analogue scale. Outcome  Overall  Control  Obese  P value  Maximum pain in mm, mean (SD)  73.7 (14.8)  71.5 (15.9)  76.1 (13.4)  0.25*  VAS in mm T0, mean (SD)  18.5 (22.5)  17.6 (21.6)  19.4 (23.8)  0.77*  VAS in mm T1, mean (SD)  47.3 (22.3)  46.2 (22.6)  48.4 (22.4)  0.72*  VAS in mm T2, mean (SD)  70.3 (18.0)  66.9 (20.2)  74.0 (15.0)  0.15*  VAS in mm T3, mean (SD)  46.1 (19.4)  40.6 (19.5)  51.7 (18.0)  0.03*  VAS in mm T4, mean (SD)  12.5 (14.0)  10.9 (13.5)  14.2 (14.6)  0.39*  Reported use of oral analgesia, n (%)  36 (65)  16 (57)  20 (74)  0.19#  Overall oral analgesia used in mg, mean (SD)  1027.3 (1094.7)  732.1 (937.7)  1333.3 (1176.7)  0.04*  Outcome  Overall  Control  Obese  P value  Maximum pain in mm, mean (SD)  73.7 (14.8)  71.5 (15.9)  76.1 (13.4)  0.25*  VAS in mm T0, mean (SD)  18.5 (22.5)  17.6 (21.6)  19.4 (23.8)  0.77*  VAS in mm T1, mean (SD)  47.3 (22.3)  46.2 (22.6)  48.4 (22.4)  0.72*  VAS in mm T2, mean (SD)  70.3 (18.0)  66.9 (20.2)  74.0 (15.0)  0.15*  VAS in mm T3, mean (SD)  46.1 (19.4)  40.6 (19.5)  51.7 (18.0)  0.03*  VAS in mm T4, mean (SD)  12.5 (14.0)  10.9 (13.5)  14.2 (14.6)  0.39*  Reported use of oral analgesia, n (%)  36 (65)  16 (57)  20 (74)  0.19#  Overall oral analgesia used in mg, mean (SD)  1027.3 (1094.7)  732.1 (937.7)  1333.3 (1176.7)  0.04*  *P value from independent t-test. #P value from chi-square test. View Large Table 2. Results on patient-reported mean maximum pain and use of oral analgesia. SD, standard deviation; VAS, visual analogue scale. Outcome  Overall  Control  Obese  P value  Maximum pain in mm, mean (SD)  73.7 (14.8)  71.5 (15.9)  76.1 (13.4)  0.25*  VAS in mm T0, mean (SD)  18.5 (22.5)  17.6 (21.6)  19.4 (23.8)  0.77*  VAS in mm T1, mean (SD)  47.3 (22.3)  46.2 (22.6)  48.4 (22.4)  0.72*  VAS in mm T2, mean (SD)  70.3 (18.0)  66.9 (20.2)  74.0 (15.0)  0.15*  VAS in mm T3, mean (SD)  46.1 (19.4)  40.6 (19.5)  51.7 (18.0)  0.03*  VAS in mm T4, mean (SD)  12.5 (14.0)  10.9 (13.5)  14.2 (14.6)  0.39*  Reported use of oral analgesia, n (%)  36 (65)  16 (57)  20 (74)  0.19#  Overall oral analgesia used in mg, mean (SD)  1027.3 (1094.7)  732.1 (937.7)  1333.3 (1176.7)  0.04*  Outcome  Overall  Control  Obese  P value  Maximum pain in mm, mean (SD)  73.7 (14.8)  71.5 (15.9)  76.1 (13.4)  0.25*  VAS in mm T0, mean (SD)  18.5 (22.5)  17.6 (21.6)  19.4 (23.8)  0.77*  VAS in mm T1, mean (SD)  47.3 (22.3)  46.2 (22.6)  48.4 (22.4)  0.72*  VAS in mm T2, mean (SD)  70.3 (18.0)  66.9 (20.2)  74.0 (15.0)  0.15*  VAS in mm T3, mean (SD)  46.1 (19.4)  40.6 (19.5)  51.7 (18.0)  0.03*  VAS in mm T4, mean (SD)  12.5 (14.0)  10.9 (13.5)  14.2 (14.6)  0.39*  Reported use of oral analgesia, n (%)  36 (65)  16 (57)  20 (74)  0.19#  Overall oral analgesia used in mg, mean (SD)  1027.3 (1094.7)  732.1 (937.7)  1333.3 (1176.7)  0.04*  *P value from independent t-test. #P value from chi-square test. View Large Multivariable regression analysis indicated that there were no significant differences between control and obese groups in terms of maximum reported pain during initial tooth alignment for a number of factors, including subject age, gender, irregularity, baseline reported pain, reported use of oral analgesia, and baseline plaque index (Table 3). However, there were significant differences between groups in terms of previous history of extractions (P = 0.045) and baseline gingival index (P = 0.010). Patients taking oral analgesics also reported slightly higher maximum pain compared to those who did not (represented by a difference of 5.98 mm in VAS scores), but this was not statistically significant (P = 0.163). Table 3. Regression analysis on the outcome of maximum reported pain during the alignment period (T0–T4) in mm in VAS scale. CI, confidence interval; Ref, reference; VAS, visual analogues scale. Factor  Univariable  Multivariable  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  4.65  −3.03, 12.32  0.24  2.64  −4.73, 10.03  0.48  Age (per year increase)        1.26  −0.54, 3.07  0.17  Gender (Ref: female)        2.07  −4.67, 8.81  0.55  Crowding at start        0.99  −0.51, 2.48  0.20  Tooth extraction (Ref: non-extraction)        −8.29  −16.39, −0.19  0.05  Baseline pain (per VAS mm increase)        0.10  −0.03, 0.24  0.13  Use of oral analgesia (Ref: no)        5.98  −2.43, 14.39  0.16  Plaque index at T0        −11.74  −24.40, 0.92  0.07  Gingival index at T0        13.17  3.21, 23.13  0.01  Factor  Univariable  Multivariable  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  4.65  −3.03, 12.32  0.24  2.64  −4.73, 10.03  0.48  Age (per year increase)        1.26  −0.54, 3.07  0.17  Gender (Ref: female)        2.07  −4.67, 8.81  0.55  Crowding at start        0.99  −0.51, 2.48  0.20  Tooth extraction (Ref: non-extraction)        −8.29  −16.39, −0.19  0.05  Baseline pain (per VAS mm increase)        0.10  −0.03, 0.24  0.13  Use of oral analgesia (Ref: no)        5.98  −2.43, 14.39  0.16  Plaque index at T0        −11.74  −24.40, 0.92  0.07  Gingival index at T0        13.17  3.21, 23.13  0.01  View Large Table 3. Regression analysis on the outcome of maximum reported pain during the alignment period (T0–T4) in mm in VAS scale. CI, confidence interval; Ref, reference; VAS, visual analogues scale. Factor  Univariable  Multivariable  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  4.65  −3.03, 12.32  0.24  2.64  −4.73, 10.03  0.48  Age (per year increase)        1.26  −0.54, 3.07  0.17  Gender (Ref: female)        2.07  −4.67, 8.81  0.55  Crowding at start        0.99  −0.51, 2.48  0.20  Tooth extraction (Ref: non-extraction)        −8.29  −16.39, −0.19  0.05  Baseline pain (per VAS mm increase)        0.10  −0.03, 0.24  0.13  Use of oral analgesia (Ref: no)        5.98  −2.43, 14.39  0.16  Plaque index at T0        −11.74  −24.40, 0.92  0.07  Gingival index at T0        13.17  3.21, 23.13  0.01  Factor  Univariable  Multivariable  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  4.65  −3.03, 12.32  0.24  2.64  −4.73, 10.03  0.48  Age (per year increase)        1.26  −0.54, 3.07  0.17  Gender (Ref: female)        2.07  −4.67, 8.81  0.55  Crowding at start        0.99  −0.51, 2.48  0.20  Tooth extraction (Ref: non-extraction)        −8.29  −16.39, −0.19  0.05  Baseline pain (per VAS mm increase)        0.10  −0.03, 0.24  0.13  Use of oral analgesia (Ref: no)        5.98  −2.43, 14.39  0.16  Plaque index at T0        −11.74  −24.40, 0.92  0.07  Gingival index at T0        13.17  3.21, 23.13  0.01  View Large Secondary outcomes (mean pain at each time-point and consumption of analgesics) Crude multivariable linear regression for mean pain at each time-point indicated that the only significant predictors for pain intensity were time (T0–T4) and reported baseline-pain (Figure 2; Table 4). However, after adjusting for confounders, obesity was associated with slightly higher (+4.47 mm in the VAS) mean pain at each time-point, which was statistically significant (P = 0.017). Additionally, the interaction between obesity and time was not statistically significant (P = 0.416), which indicates that although obese patients reported slightly higher pain than normal-weight patients at all time-points, the pain variation across time-points per se was similar in both groups. Figure 2. View largeDownload slide Graph showing the predicted mean pain at each time-point T0–T4 (mm in VAS) from the multivariable regression analysis. CI, confidence interval; VAS, visual analogue scale. Figure 2. View largeDownload slide Graph showing the predicted mean pain at each time-point T0–T4 (mm in VAS) from the multivariable regression analysis. CI, confidence interval; VAS, visual analogue scale. Table 4. Regression analysis on the outcome of reported pain at each time-point in mm in VAS scale. CI, confidence interval; Ref, reference; VAS, visual analogues scale.   Multivariable model 1  Multivariable model 2  Factor  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  3.52  −3.05, 10.09  0.29  4.42  0.79, 8.05  0.02  Time-point*   T0  Ref             T1  28.82  23.17, 34.47  <0.001  28.81  23.17, 34.47  <0.001   T2  51.85  44.71, 59.00  <0.001  51.85  44.71, 59.00  <0.001   T3  27.58  20.22, 34.94  <0.001  27.58  20.22, 34.94  <0.001   T4  −5.95  −11.60, −0.29  0.04  −5.95  −11.60, −0.29  0.04  Age (per year increase)        0.77  −0.25, 1.78  0.14  Gender (Ref: male)        1.96  −1.78, 5.70  0.30  Crowding (per mm increase)        −0.46  −1.26, 0.35  0.27  Tooth extraction (Ref: non-extraction)        −2.62  −6.58, 1.34  0.19  Baseline pain (per VAS mm increase)        0.43  0.34, 0.52  <0.001  Use of oral analgesia (Ref: no)        4.34  0.02, 8.67  0.05  Plaque index at T0        −5.36  −13.35, 2.63  0.19  Gingival index at T0        2.69  −2.82, 8.20  0.34    Multivariable model 1  Multivariable model 2  Factor  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  3.52  −3.05, 10.09  0.29  4.42  0.79, 8.05  0.02  Time-point*   T0  Ref             T1  28.82  23.17, 34.47  <0.001  28.81  23.17, 34.47  <0.001   T2  51.85  44.71, 59.00  <0.001  51.85  44.71, 59.00  <0.001   T3  27.58  20.22, 34.94  <0.001  27.58  20.22, 34.94  <0.001   T4  −5.95  −11.60, −0.29  0.04  −5.95  −11.60, −0.29  0.04  Age (per year increase)        0.77  −0.25, 1.78  0.14  Gender (Ref: male)        1.96  −1.78, 5.70  0.30  Crowding (per mm increase)        −0.46  −1.26, 0.35  0.27  Tooth extraction (Ref: non-extraction)        −2.62  −6.58, 1.34  0.19  Baseline pain (per VAS mm increase)        0.43  0.34, 0.52  <0.001  Use of oral analgesia (Ref: no)        4.34  0.02, 8.67  0.05  Plaque index at T0        −5.36  −13.35, 2.63  0.19  Gingival index at T0        2.69  −2.82, 8.20  0.34  *Interaction of obesity with time found to be non-significant (P = 0.42) and was dropped from the model. View Large Table 4. Regression analysis on the outcome of reported pain at each time-point in mm in VAS scale. CI, confidence interval; Ref, reference; VAS, visual analogues scale.   Multivariable model 1  Multivariable model 2  Factor  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  3.52  −3.05, 10.09  0.29  4.42  0.79, 8.05  0.02  Time-point*   T0  Ref             T1  28.82  23.17, 34.47  <0.001  28.81  23.17, 34.47  <0.001   T2  51.85  44.71, 59.00  <0.001  51.85  44.71, 59.00  <0.001   T3  27.58  20.22, 34.94  <0.001  27.58  20.22, 34.94  <0.001   T4  −5.95  −11.60, −0.29  0.04  −5.95  −11.60, −0.29  0.04  Age (per year increase)        0.77  −0.25, 1.78  0.14  Gender (Ref: male)        1.96  −1.78, 5.70  0.30  Crowding (per mm increase)        −0.46  −1.26, 0.35  0.27  Tooth extraction (Ref: non-extraction)        −2.62  −6.58, 1.34  0.19  Baseline pain (per VAS mm increase)        0.43  0.34, 0.52  <0.001  Use of oral analgesia (Ref: no)        4.34  0.02, 8.67  0.05  Plaque index at T0        −5.36  −13.35, 2.63  0.19  Gingival index at T0        2.69  −2.82, 8.20  0.34    Multivariable model 1  Multivariable model 2  Factor  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  3.52  −3.05, 10.09  0.29  4.42  0.79, 8.05  0.02  Time-point*   T0  Ref             T1  28.82  23.17, 34.47  <0.001  28.81  23.17, 34.47  <0.001   T2  51.85  44.71, 59.00  <0.001  51.85  44.71, 59.00  <0.001   T3  27.58  20.22, 34.94  <0.001  27.58  20.22, 34.94  <0.001   T4  −5.95  −11.60, −0.29  0.04  −5.95  −11.60, −0.29  0.04  Age (per year increase)        0.77  −0.25, 1.78  0.14  Gender (Ref: male)        1.96  −1.78, 5.70  0.30  Crowding (per mm increase)        −0.46  −1.26, 0.35  0.27  Tooth extraction (Ref: non-extraction)        −2.62  −6.58, 1.34  0.19  Baseline pain (per VAS mm increase)        0.43  0.34, 0.52  <0.001  Use of oral analgesia (Ref: no)        4.34  0.02, 8.67  0.05  Plaque index at T0        −5.36  −13.35, 2.63  0.19  Gingival index at T0        2.69  −2.82, 8.20  0.34  *Interaction of obesity with time found to be non-significant (P = 0.42) and was dropped from the model. View Large Analysis of the consumption of oral analgesics (as a binary outcome) revealed no statistically significant association in either the univariable or the multivariable (adjusted) analyses (Supplementary Table S1). Analysis of the total amount of analgesics consumed (as a continuous outcome) revealed statistically significant associations with obesity for both univariable and multivariable (adjusted) analyses (+601.20 mg, P = 0.035 and +646.38 mg, P = 0.023, respectively). There was also a significant association with age in the multivariable analysis, with older patients taking smaller amounts of analgesics (P = 0.018; Supplementary Table S2). After accounting for confounders, obese patients were associated with higher odds of taking analgesics (OR = 1.92) as well as a higher overall amount of consumed oral analgesics (difference = 648.38 mg), although only the latter was statistically significant. Subgroup analysis by gender Subgroup analyses by gender indicated that pain differences between obese and non-obese subjects related mostly to males rather than females, which was true for both maximum pain across time-points (Supplementary Table S3) and mean pain at each time-point (Supplementary Table S4). However, these differences between males and females were not consistently significant (see interaction terms). Additionally, caution is warranted with the interpretation of this subgroup analysis, due to its post hoc nature and the fact that this analysis further diminishes the statistical power of this study. Agreement/reliability of the method Agreement between repeated VAS measurements was found to be very good with an average difference of −0.86, with 95 per cent limits of agreement of −6.14 to 4.42 mm, and no signs of systematic effects (Supplementary Figure S1a). The reliability of the method was likewise very good, with a concordance correlation coefficient of 0.995 and 95% CI of 0.994 to 0.996 (Supplementary Figure S1b). Discussion The commonality of obesity in Western society means that the implications of this condition are likely to affect increasing areas of modern health care and therefore, it is important that clinicians from all specialties understand potential issues associated with the care of obese patients. In the present study, we have investigated orthodontic pain during the first week following the placement of fixed orthodontic appliances in normal-weight and obese children. We found that maximum reported pain across the observation period was not significantly different between the two groups. However, mean maximum pain was higher in the obese group when compared to normal-weight patients at all individual time-points. This general trend for higher pain at each time point and the fact that obesity did not have a modifying effect on the progression of pain through the alignment phase (interaction P > 0.05) suggests that obese patients experienced generally higher pain levels than normal-weight patients. In addition, total analgesia taken by the obese group was also significantly higher than in the normal-weight cohort. These data suggest that obese patients may be more susceptible to orthodontic pain during the first week of treatment with fixed appliances and that orthodontists should take this into account during treatment of this patient group. We found a pattern of orofacial pain intensity during this first week following placement of fixed-appliances similar to that seen in previous investigations (12, 15, 16). This reinforces the consistency of pain response that is observed following placement of fixed orthodontic appliances and makes this a useful experimental model to investigate orofacial pain (12, 15, 16, 18). The prospective design (30) and comparability of the experimental groups at baseline can also be considered strengths of the present study. Moreover, obesity was defined according to widely accepted and reliable measures, which makes misclassification unlikely. Additionally, as the patients in the obese and normal-weight groups were similar apart from their BMI, no drop-outs were seen and VAS measurement blinding was implemented, the respective risk for selection, attrition, and detection bias is low. This is part of a larger prospective investigation of orthodontic treatment response in normal-weight and obese subjects, with a primary sample size calculation based upon rate of orthodontic tooth alignment (31). However, post hoc analysis indicated that this study had 96 per cent power to identify the specified effect on the outcome of maximum-pain experience. Although we did not investigate orthodontic pain in the longer-term, there is evidence to indicate that there is consistency in the pattern during subsequent archwire changes (12, 15, 16). The relationship between obesity and oral disease is complex, but associations with reduced tooth number and irregular dental visits (32), periodontal disease (33–35), and dental caries status (36) have all been described. Moreover, the presence of oral disease seems to have a greater negative impact on quality-of-life in the morbidly obese when compared to normal-weight subjects (37). Although the implications of obesity for orthodontic therapy are less clear, a number of potential associated factors have been discussed that may impact on treatment, which include psychosocial well-being, altered craniofacial growth, overall tissue turnover, and bone metabolism (38–41). The results of this investigation suggest that there are differences in the pain response between obese and normal-weight subjects during orthodontic treatment over the short-term with corresponding differences in the consumption of analgesics. This is in agreement with previous studies, which report that obesity can influence peripheral pain perception and be a contributory factor for increased pain thresholds (5–8). Possible explanations for this relationship include amongst others, peripheral factors such as skin thickness and innervation density, (42) a possible nociceptive modulation through leptin (43) or interaction of ghrelin with central opioid mechanisms, which seems to have an anti-nociceptive effect on endogenous opioids (44). In any case, prolonged orthodontic pain has been shown to have potential negative consequences on compliance (45) and treatment completion (46, 47). As oral analgesics are effective in reducing orthodontic pain (48) it would seem prudent for clinicians to ensure that obese patients are provided with the necessary information and measures to ensure appropriate pain relief following the placement of fixed-appliances. It is premature to suggest that obesity is a clear risk factor for more pain with fixed appliances but within the context of evidence linking obesity with poor compliance (49), it invites speculation that this condition might present different challenges for orthodontists. This is the first prospective study to investigate orthodontic pain in association with variation in body weight and provides evidence that informs clinical practice, both in orthodontics and other areas of medicine and dentistry. The results of this study are widely generalizable and applicable to the majority of obese and normal-weight children aged between 12 and 18 years. Conclusions Based on the results of this prospective cohort study on pain experience during alignment in obese and normal-weight children with moderate-to-severe mandibular incisor irregularity, the following can be concluded: The maximum-pain experienced during alignment in obese patients seems to be slightly higher than normal-weight patients, but this is not statistically significant; Obese patients experience statistically higher mean pain than normal-weight patients at each time-point during the first week after appliance placement; and This was accompanied by a corresponding statistically significant higher consumption of pain medication. Supplementary material Supplementary data are available at European Journal of Orthodontics online. Funding This work was supported by the Ministry of Higher Education and Scientific Research of Iraq through an educational scholarship to HS. Conflict of interest None to declare. 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The effect of obesity on orofacial pain during early orthodontic treatment with fixed appliances: a prospective cohort study

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© The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com
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Abstract

Summary Introduction We have investigated orofacial pain in a prospective cohort of obese and normal-weight subjects undergoing fixed-appliance orthodontic treatment. Methods Fifty-five subjects (27 males, 28 females) mean age 15.1 (1.6) years and mean body mass index 30.2 (3.5) in obese and 19.4 (2.2) kg/m2 in normal-weight groups were followed for 1 week after appliance placement. Primary outcome was maximum-pain measured using a 100-mm visual analogue scale. Secondary outcomes included mean pain and oral analgesic consumption. Results Mean maximum pain for the total sample was 73.7 (standard deviation 14.8; 95% confidence interval 69.8–77.7) mm with no significant differences among groups (P = 0.247). However, mean maximum pain was higher at all time-points for the obese group and significant at 72 hours (P = 0.034). Total analgesia consumed by the obese group was also significantly higher than normal weight (P = 0.041). Multivariable regression found the only significant predictor for mean pain was time. After adjusting for confounding, obesity was associated with higher (+4.47 mm) mean pain at each time-point (P = 0.018). A significant association existed between obesity and total analgesic consumption (univariable-analysis, P = 0.035; multivariable analysis, P = 0.023). After accounting for confounders, obese patients were associated with taking a higher quantity of oral analgesics. Conclusions We found a trend towards increased mean pain and an association with increased analgesic consumption in obese subjects during the first week following fixed-appliance placement. Introduction Obesity is a specific disease state characterized by chronic subclinical inflammation mediated through excess adipose accumulation and the concomitant production of systemic proinflammatory factors (1). There has been a steady rise in obesity associated with Western societies during the last few decades, which represents a major health care challenge because of the significant associations between obesity and multiple chronic diseases (2). A wide range of risk factors have been associated with obesity, particularly a sedentary lifestyle and the consumption of high-calorific food, with adverse lifestyle patterns often established from early childhood (3). Obesity in children and young adults has also been associated with poor mental health and psychosocial problems, including depression, anxiety, and low self-esteem. There is an established relationship between obesity and chronic musculoskeletal pain, which can also manifest from childhood; (4) and there are also suggestions that obesity can influence peripheral pain perception, being a contributory factor for increased pain thresholds (5–8). Orofacial pain is a common adverse effect of orthodontic treatment with fixed-appliances, particularly during the first few days after placement (9–16). Archwire progression during treatment often produces further episodes of pain, which can collectively affect eating and sleeping, and impact on day-to-day activities (9). A number of studies have investigated the effect of different fixed-appliance systems on orthodontic pain, but there is little evidence to suggest that any particular appliance combination is associated with less pain than any other (12, 13, 15, 17–20). However, orthodontic pain during the first week following the placement of fixed-appliances has been shown to have a consistent and reproducible profile, increasing during the first 24 to 72 hours and then reducing to baseline levels after a week, (12, 15, 16, 18) which, provides a useful experimental model to investigate orofacial pain experience in different subjects. The purpose of the present study was to investigate the effect of obesity on pain in subjects undertaking routine orthodontic treatment with fixed-appliances. Specifically, this prospective cohort study compared orthodontic pain experience during the first week of fixed-appliance therapy in two groups of children aged between 12 and 18 years and classified as normal weight and obese based upon body mass index (BMI). Materials and methods Study design This prospective cohort study compared the effects of obesity on orthodontic pain experience during initial tooth alignment with fixed-appliances. Ethical approval was obtained from the United Kingdom National Research Ethics Service (14/LO/0769) and written informed consent was received from all parents, guardians, and children. We report and present data according to the STROBE statement (21). Setting Participants were recruited from those attending for routine fixed-appliance orthodontic treatment in the Department of Orthodontics at King’s College London Dental Institute between January 2015 and June 2016. Follow up for this investigation covered the period from acquisition of baseline records and appliance placement up to the completion of tooth alignment (placement of a 0.019 × 0.025-inch stainless steel rectangular archwire in the lower arch). Data collection for this part of the investigation took place during the week immediately following placement of fixed orthodontic appliances for each participant. Participants Eligibility for inclusion in this study included patients with the following criteria: (1) 12 to 18 years old at the start of treatment; (2) no medical contraindications or the taking of regular medication (including antibiotic therapy in the previous 6 months); (3) in the permanent dentition, and (4) moderate-to-severe mandibular arch incisor irregularity (4–12 mm). Following informed consent, the body weight of subjects was measured to the nearest 0.1 kilogram (kg) using a calibrated scale and height was measured to the nearest centimetre (cm) using a wall-mounted rule. BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2). United Kingdom Royal College of Pediatrics and Child Health/World Health Organization growth charts were used to calculate and classify BMI centile in relation to age and sex (22). All measurements were taken by a single trained operator (HFS). Variables Subjects were classified as normal weight (BMI centile 2–91) and obese (BMI centile > 98). Those classified as underweight (BMI centile < 2) and overweight (BMI centile 91–98) were excluded from the study, respectively. Baseline tooth alignment prior to the start of treatment was calculated from a scanned dental stone cast using an irregularity-index, which measures the horizontal linear contact-point displacement of each mandibular incisor from the adjacent tooth and therefore represents the sum of the five individual displacements (23). Periodontal health was measured clinically using established validated gingival and plaque indices (24, 25). The bonding method and fixed-appliance protocol was standardized between groups (MBT prescription pre-coated 3M Victory 0.022-inch brackets, 3M Unitek, Monrovia, USA). After bracket bonding, a 0.014-inch nickel titanium archwire was tied in to the lower dental arch and ligated using conventional elastomerics. The archwire was cut distal to the first molar teeth and not cinched. No bite planes, auxiliary arches, intermaxillary elastics, headgears, or temporary anchorage devices were used during the period of investigation. All appliances were placed by postgraduate orthodontic trainees under the direct supervision of a consultant orthodontist. Patients were provided with a pain diary to complete over the week following placement of the fixed-appliance. The diary recorded orthodontic pain immediately after appliance placement (T0), at 4 hours (T1), 24-hours (T2), 72-hours (T3), and 1-week (T4) following the appointment by means of a 100 millimetre (mm) visual analogue scale (VAS) using the terms ‘Very comfortable’ and ‘Very uncomfortable’ as peripheral weightings (26). The VAS score is the distance from the left end of the line to the point of the subjects’ mark, measured to the nearest mm. Each VAS score was measured on two separate occasions by the same operator (HFS); with the mean of the two measurements taken as the representative value. In addition to the VAS score, subjects noted the consumption and dosage of oral analgesics during the period of observation. Each subject was free to take non-prescription oral analgesia as required. The pain diary was completed by the patient and returned at the following appointment. The primary outcome measure was maximum-pain experience during initial alignment with fixed orthodontic appliances, whilst secondary outcomes were (1) mean pain at each time-point, (2) use of analgesics, and (3) number of analgesics taken during this period of treatment. There were no changes to outcomes following study commencement. Pain diaries were coded appropriately so that both outcome assessor (HFS) and person responsible for the statistical analysis (SNP) were blinded to subject classification. Data coding was broken after the end of the analysis and no breach of blinding was identified. All VAS measurements were extracted in duplicate 2 weeks apart and agreement/reliability were assessed with the Bland–Altman limits of agreement (27) and the concordance correlation coefficient (28), respectively. Study size Study size calculation for this investigation was based upon the outcome of initial rate of orthodontic tooth alignment, which gave a required sample of 23 per group and has been described previously (29). A post hoc power analysis was performed to assess, if this study had sufficient sample to identify a set 30 per cent difference in maximum pain in obese compared to normal-weight patients. Baseline maximum pain (74.63 mm) and common standard deviation (SD) for both groups (21.95 mm) originated from a previous study in the same clinical setting (16), while alpha for the independent t-test was set at 5 per cent. The results of the power analysis indicated that the present study has 96 per cent power to identify the specified effect on the primary outcome of maximum-pain experience. Statistical methods Descriptive statistics were calculated to characterize the experimental groups, including means and SDs for continuous variables and frequencies for binary outcomes, after checking for normal distribution. Initial crude differences in baseline and outcome data were calculated with independent t-tests and chi-square tests. The effect of obesity on the primary outcome (maximum-pain experienced during alignment) and all secondary outcomes was investigated using univariable (crude) and multivariable generalized estimation equation regression models with robust standard errors, adjusted for the confounding effect of baseline data (sex, age, baseline-irregularity, baseline-pain), and co-interventions (previous tooth extraction and use of analgesia during alignment). Results are reported as unstandardized coefficients or odds ratios (ORs) for continuous and binary outcomes, respectively. In the analysis of mean pain across time-points, the model accounted for within-patient and time-point correlations. Analysis of residuals was conducted to confirm no violation of the linear regression assumptions. A post hoc subgroup analysis by gender was conducted, but is reported only briefly, due to the lack of statistical power. All analyses were carried out using Stata 12.0 (Statacorp, College Station, Texas, USA). A two-tailed P value of 0.05 was considered statistically significant with a 95% confidence interval (CI) for all tests. Results Participants This prospective cohort study included 55 patients (27 male and 28 female) with a mean age of 15.1 (SD, 1.6) years and mean irregularity index of 7.6 (SD 2.4; 95% CI 6.9–8.2) mm. No patient drop-outs existed during the study period and all distributed pain diaries were collected and analysed. Mean overall BMI of the cohort was 24.7 (SD 6.2) kg/m2. Table 1 shows baseline demographics and clinical characteristics of the two cohorts at start of treatment. The normal-weight group had a mean BMI of 19.4 (2.2) whilst the obese group had a mean BMI of 30.2 (3.5) kg/m2. Apart from BMI, there were no significant differences among groups for baseline characteristics. Table 1. Baseline demographics of subjects included in the study. SD, standard deviation; BMI, body mass index.   Overall  Control  Obese  P value  Patients  55  28  27    Male/female, n  27/28  15/13  12/15  0.50*  Age, mean (SD)  15.1 (1.7)  15.1 (1.6)  15.1 (1.9)  0.99#  Plaque index (SD)  0.56 (0.32)  0.57 (0.32)  0.54 (0.31)  0.75#  Gingival index (SD)  0.74 (0.39)  0.74 (0.40)  0.73 (0.38)  0.93#  Crowding, mean (SD)  7.6 (2.4)  7.0 (2.3)  8.2 (2.4)  0.06#  BMI, mean (SD)  24.7 (6.2)  19.4 (2.2)  30.2 (3.5)  <0.001#  Tooth extraction, n (%)  8 (15%)  4 (14%)  4 (15%)  0.96*    Overall  Control  Obese  P value  Patients  55  28  27    Male/female, n  27/28  15/13  12/15  0.50*  Age, mean (SD)  15.1 (1.7)  15.1 (1.6)  15.1 (1.9)  0.99#  Plaque index (SD)  0.56 (0.32)  0.57 (0.32)  0.54 (0.31)  0.75#  Gingival index (SD)  0.74 (0.39)  0.74 (0.40)  0.73 (0.38)  0.93#  Crowding, mean (SD)  7.6 (2.4)  7.0 (2.3)  8.2 (2.4)  0.06#  BMI, mean (SD)  24.7 (6.2)  19.4 (2.2)  30.2 (3.5)  <0.001#  Tooth extraction, n (%)  8 (15%)  4 (14%)  4 (15%)  0.96*  *P value from chi-square test. #P value from independent t-test. View Large Table 1. Baseline demographics of subjects included in the study. SD, standard deviation; BMI, body mass index.   Overall  Control  Obese  P value  Patients  55  28  27    Male/female, n  27/28  15/13  12/15  0.50*  Age, mean (SD)  15.1 (1.7)  15.1 (1.6)  15.1 (1.9)  0.99#  Plaque index (SD)  0.56 (0.32)  0.57 (0.32)  0.54 (0.31)  0.75#  Gingival index (SD)  0.74 (0.39)  0.74 (0.40)  0.73 (0.38)  0.93#  Crowding, mean (SD)  7.6 (2.4)  7.0 (2.3)  8.2 (2.4)  0.06#  BMI, mean (SD)  24.7 (6.2)  19.4 (2.2)  30.2 (3.5)  <0.001#  Tooth extraction, n (%)  8 (15%)  4 (14%)  4 (15%)  0.96*    Overall  Control  Obese  P value  Patients  55  28  27    Male/female, n  27/28  15/13  12/15  0.50*  Age, mean (SD)  15.1 (1.7)  15.1 (1.6)  15.1 (1.9)  0.99#  Plaque index (SD)  0.56 (0.32)  0.57 (0.32)  0.54 (0.31)  0.75#  Gingival index (SD)  0.74 (0.39)  0.74 (0.40)  0.73 (0.38)  0.93#  Crowding, mean (SD)  7.6 (2.4)  7.0 (2.3)  8.2 (2.4)  0.06#  BMI, mean (SD)  24.7 (6.2)  19.4 (2.2)  30.2 (3.5)  <0.001#  Tooth extraction, n (%)  8 (15%)  4 (14%)  4 (15%)  0.96*  *P value from chi-square test. #P value from independent t-test. View Large Primary outcome (maximum-pain intensity during alignment) Mean maximum-pain intensity across all time-points for the total sample was 73.7 mm (Figure 1; SD 14.8; 95% CI 69.8–77.7) with no significant differences among groups (Table 2; P = 0.247). Reported mean maximum pain was higher at all time-points for the obese group compared to control with a statistically significant difference at T3 (P = 0.034; Table 2). A greater percentage of the obese group reported taking oral analgesia when compared to control (74 versus 57 per cent), but this difference was not significant (P = 0.187). Figure 1. View largeDownload slide Box plot showing the predicted maximum pain during the whole alignment period (mm in VAS) from the multivariable regression analysis. VAS, visual analogue scale. Figure 1. View largeDownload slide Box plot showing the predicted maximum pain during the whole alignment period (mm in VAS) from the multivariable regression analysis. VAS, visual analogue scale. Table 2. Results on patient-reported mean maximum pain and use of oral analgesia. SD, standard deviation; VAS, visual analogue scale. Outcome  Overall  Control  Obese  P value  Maximum pain in mm, mean (SD)  73.7 (14.8)  71.5 (15.9)  76.1 (13.4)  0.25*  VAS in mm T0, mean (SD)  18.5 (22.5)  17.6 (21.6)  19.4 (23.8)  0.77*  VAS in mm T1, mean (SD)  47.3 (22.3)  46.2 (22.6)  48.4 (22.4)  0.72*  VAS in mm T2, mean (SD)  70.3 (18.0)  66.9 (20.2)  74.0 (15.0)  0.15*  VAS in mm T3, mean (SD)  46.1 (19.4)  40.6 (19.5)  51.7 (18.0)  0.03*  VAS in mm T4, mean (SD)  12.5 (14.0)  10.9 (13.5)  14.2 (14.6)  0.39*  Reported use of oral analgesia, n (%)  36 (65)  16 (57)  20 (74)  0.19#  Overall oral analgesia used in mg, mean (SD)  1027.3 (1094.7)  732.1 (937.7)  1333.3 (1176.7)  0.04*  Outcome  Overall  Control  Obese  P value  Maximum pain in mm, mean (SD)  73.7 (14.8)  71.5 (15.9)  76.1 (13.4)  0.25*  VAS in mm T0, mean (SD)  18.5 (22.5)  17.6 (21.6)  19.4 (23.8)  0.77*  VAS in mm T1, mean (SD)  47.3 (22.3)  46.2 (22.6)  48.4 (22.4)  0.72*  VAS in mm T2, mean (SD)  70.3 (18.0)  66.9 (20.2)  74.0 (15.0)  0.15*  VAS in mm T3, mean (SD)  46.1 (19.4)  40.6 (19.5)  51.7 (18.0)  0.03*  VAS in mm T4, mean (SD)  12.5 (14.0)  10.9 (13.5)  14.2 (14.6)  0.39*  Reported use of oral analgesia, n (%)  36 (65)  16 (57)  20 (74)  0.19#  Overall oral analgesia used in mg, mean (SD)  1027.3 (1094.7)  732.1 (937.7)  1333.3 (1176.7)  0.04*  *P value from independent t-test. #P value from chi-square test. View Large Table 2. Results on patient-reported mean maximum pain and use of oral analgesia. SD, standard deviation; VAS, visual analogue scale. Outcome  Overall  Control  Obese  P value  Maximum pain in mm, mean (SD)  73.7 (14.8)  71.5 (15.9)  76.1 (13.4)  0.25*  VAS in mm T0, mean (SD)  18.5 (22.5)  17.6 (21.6)  19.4 (23.8)  0.77*  VAS in mm T1, mean (SD)  47.3 (22.3)  46.2 (22.6)  48.4 (22.4)  0.72*  VAS in mm T2, mean (SD)  70.3 (18.0)  66.9 (20.2)  74.0 (15.0)  0.15*  VAS in mm T3, mean (SD)  46.1 (19.4)  40.6 (19.5)  51.7 (18.0)  0.03*  VAS in mm T4, mean (SD)  12.5 (14.0)  10.9 (13.5)  14.2 (14.6)  0.39*  Reported use of oral analgesia, n (%)  36 (65)  16 (57)  20 (74)  0.19#  Overall oral analgesia used in mg, mean (SD)  1027.3 (1094.7)  732.1 (937.7)  1333.3 (1176.7)  0.04*  Outcome  Overall  Control  Obese  P value  Maximum pain in mm, mean (SD)  73.7 (14.8)  71.5 (15.9)  76.1 (13.4)  0.25*  VAS in mm T0, mean (SD)  18.5 (22.5)  17.6 (21.6)  19.4 (23.8)  0.77*  VAS in mm T1, mean (SD)  47.3 (22.3)  46.2 (22.6)  48.4 (22.4)  0.72*  VAS in mm T2, mean (SD)  70.3 (18.0)  66.9 (20.2)  74.0 (15.0)  0.15*  VAS in mm T3, mean (SD)  46.1 (19.4)  40.6 (19.5)  51.7 (18.0)  0.03*  VAS in mm T4, mean (SD)  12.5 (14.0)  10.9 (13.5)  14.2 (14.6)  0.39*  Reported use of oral analgesia, n (%)  36 (65)  16 (57)  20 (74)  0.19#  Overall oral analgesia used in mg, mean (SD)  1027.3 (1094.7)  732.1 (937.7)  1333.3 (1176.7)  0.04*  *P value from independent t-test. #P value from chi-square test. View Large Multivariable regression analysis indicated that there were no significant differences between control and obese groups in terms of maximum reported pain during initial tooth alignment for a number of factors, including subject age, gender, irregularity, baseline reported pain, reported use of oral analgesia, and baseline plaque index (Table 3). However, there were significant differences between groups in terms of previous history of extractions (P = 0.045) and baseline gingival index (P = 0.010). Patients taking oral analgesics also reported slightly higher maximum pain compared to those who did not (represented by a difference of 5.98 mm in VAS scores), but this was not statistically significant (P = 0.163). Table 3. Regression analysis on the outcome of maximum reported pain during the alignment period (T0–T4) in mm in VAS scale. CI, confidence interval; Ref, reference; VAS, visual analogues scale. Factor  Univariable  Multivariable  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  4.65  −3.03, 12.32  0.24  2.64  −4.73, 10.03  0.48  Age (per year increase)        1.26  −0.54, 3.07  0.17  Gender (Ref: female)        2.07  −4.67, 8.81  0.55  Crowding at start        0.99  −0.51, 2.48  0.20  Tooth extraction (Ref: non-extraction)        −8.29  −16.39, −0.19  0.05  Baseline pain (per VAS mm increase)        0.10  −0.03, 0.24  0.13  Use of oral analgesia (Ref: no)        5.98  −2.43, 14.39  0.16  Plaque index at T0        −11.74  −24.40, 0.92  0.07  Gingival index at T0        13.17  3.21, 23.13  0.01  Factor  Univariable  Multivariable  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  4.65  −3.03, 12.32  0.24  2.64  −4.73, 10.03  0.48  Age (per year increase)        1.26  −0.54, 3.07  0.17  Gender (Ref: female)        2.07  −4.67, 8.81  0.55  Crowding at start        0.99  −0.51, 2.48  0.20  Tooth extraction (Ref: non-extraction)        −8.29  −16.39, −0.19  0.05  Baseline pain (per VAS mm increase)        0.10  −0.03, 0.24  0.13  Use of oral analgesia (Ref: no)        5.98  −2.43, 14.39  0.16  Plaque index at T0        −11.74  −24.40, 0.92  0.07  Gingival index at T0        13.17  3.21, 23.13  0.01  View Large Table 3. Regression analysis on the outcome of maximum reported pain during the alignment period (T0–T4) in mm in VAS scale. CI, confidence interval; Ref, reference; VAS, visual analogues scale. Factor  Univariable  Multivariable  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  4.65  −3.03, 12.32  0.24  2.64  −4.73, 10.03  0.48  Age (per year increase)        1.26  −0.54, 3.07  0.17  Gender (Ref: female)        2.07  −4.67, 8.81  0.55  Crowding at start        0.99  −0.51, 2.48  0.20  Tooth extraction (Ref: non-extraction)        −8.29  −16.39, −0.19  0.05  Baseline pain (per VAS mm increase)        0.10  −0.03, 0.24  0.13  Use of oral analgesia (Ref: no)        5.98  −2.43, 14.39  0.16  Plaque index at T0        −11.74  −24.40, 0.92  0.07  Gingival index at T0        13.17  3.21, 23.13  0.01  Factor  Univariable  Multivariable  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  4.65  −3.03, 12.32  0.24  2.64  −4.73, 10.03  0.48  Age (per year increase)        1.26  −0.54, 3.07  0.17  Gender (Ref: female)        2.07  −4.67, 8.81  0.55  Crowding at start        0.99  −0.51, 2.48  0.20  Tooth extraction (Ref: non-extraction)        −8.29  −16.39, −0.19  0.05  Baseline pain (per VAS mm increase)        0.10  −0.03, 0.24  0.13  Use of oral analgesia (Ref: no)        5.98  −2.43, 14.39  0.16  Plaque index at T0        −11.74  −24.40, 0.92  0.07  Gingival index at T0        13.17  3.21, 23.13  0.01  View Large Secondary outcomes (mean pain at each time-point and consumption of analgesics) Crude multivariable linear regression for mean pain at each time-point indicated that the only significant predictors for pain intensity were time (T0–T4) and reported baseline-pain (Figure 2; Table 4). However, after adjusting for confounders, obesity was associated with slightly higher (+4.47 mm in the VAS) mean pain at each time-point, which was statistically significant (P = 0.017). Additionally, the interaction between obesity and time was not statistically significant (P = 0.416), which indicates that although obese patients reported slightly higher pain than normal-weight patients at all time-points, the pain variation across time-points per se was similar in both groups. Figure 2. View largeDownload slide Graph showing the predicted mean pain at each time-point T0–T4 (mm in VAS) from the multivariable regression analysis. CI, confidence interval; VAS, visual analogue scale. Figure 2. View largeDownload slide Graph showing the predicted mean pain at each time-point T0–T4 (mm in VAS) from the multivariable regression analysis. CI, confidence interval; VAS, visual analogue scale. Table 4. Regression analysis on the outcome of reported pain at each time-point in mm in VAS scale. CI, confidence interval; Ref, reference; VAS, visual analogues scale.   Multivariable model 1  Multivariable model 2  Factor  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  3.52  −3.05, 10.09  0.29  4.42  0.79, 8.05  0.02  Time-point*   T0  Ref             T1  28.82  23.17, 34.47  <0.001  28.81  23.17, 34.47  <0.001   T2  51.85  44.71, 59.00  <0.001  51.85  44.71, 59.00  <0.001   T3  27.58  20.22, 34.94  <0.001  27.58  20.22, 34.94  <0.001   T4  −5.95  −11.60, −0.29  0.04  −5.95  −11.60, −0.29  0.04  Age (per year increase)        0.77  −0.25, 1.78  0.14  Gender (Ref: male)        1.96  −1.78, 5.70  0.30  Crowding (per mm increase)        −0.46  −1.26, 0.35  0.27  Tooth extraction (Ref: non-extraction)        −2.62  −6.58, 1.34  0.19  Baseline pain (per VAS mm increase)        0.43  0.34, 0.52  <0.001  Use of oral analgesia (Ref: no)        4.34  0.02, 8.67  0.05  Plaque index at T0        −5.36  −13.35, 2.63  0.19  Gingival index at T0        2.69  −2.82, 8.20  0.34    Multivariable model 1  Multivariable model 2  Factor  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  3.52  −3.05, 10.09  0.29  4.42  0.79, 8.05  0.02  Time-point*   T0  Ref             T1  28.82  23.17, 34.47  <0.001  28.81  23.17, 34.47  <0.001   T2  51.85  44.71, 59.00  <0.001  51.85  44.71, 59.00  <0.001   T3  27.58  20.22, 34.94  <0.001  27.58  20.22, 34.94  <0.001   T4  −5.95  −11.60, −0.29  0.04  −5.95  −11.60, −0.29  0.04  Age (per year increase)        0.77  −0.25, 1.78  0.14  Gender (Ref: male)        1.96  −1.78, 5.70  0.30  Crowding (per mm increase)        −0.46  −1.26, 0.35  0.27  Tooth extraction (Ref: non-extraction)        −2.62  −6.58, 1.34  0.19  Baseline pain (per VAS mm increase)        0.43  0.34, 0.52  <0.001  Use of oral analgesia (Ref: no)        4.34  0.02, 8.67  0.05  Plaque index at T0        −5.36  −13.35, 2.63  0.19  Gingival index at T0        2.69  −2.82, 8.20  0.34  *Interaction of obesity with time found to be non-significant (P = 0.42) and was dropped from the model. View Large Table 4. Regression analysis on the outcome of reported pain at each time-point in mm in VAS scale. CI, confidence interval; Ref, reference; VAS, visual analogues scale.   Multivariable model 1  Multivariable model 2  Factor  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  3.52  −3.05, 10.09  0.29  4.42  0.79, 8.05  0.02  Time-point*   T0  Ref             T1  28.82  23.17, 34.47  <0.001  28.81  23.17, 34.47  <0.001   T2  51.85  44.71, 59.00  <0.001  51.85  44.71, 59.00  <0.001   T3  27.58  20.22, 34.94  <0.001  27.58  20.22, 34.94  <0.001   T4  −5.95  −11.60, −0.29  0.04  −5.95  −11.60, −0.29  0.04  Age (per year increase)        0.77  −0.25, 1.78  0.14  Gender (Ref: male)        1.96  −1.78, 5.70  0.30  Crowding (per mm increase)        −0.46  −1.26, 0.35  0.27  Tooth extraction (Ref: non-extraction)        −2.62  −6.58, 1.34  0.19  Baseline pain (per VAS mm increase)        0.43  0.34, 0.52  <0.001  Use of oral analgesia (Ref: no)        4.34  0.02, 8.67  0.05  Plaque index at T0        −5.36  −13.35, 2.63  0.19  Gingival index at T0        2.69  −2.82, 8.20  0.34    Multivariable model 1  Multivariable model 2  Factor  Coefficient  95% CI  P  Coefficient  95% CI  P  Obesity group (Ref: normal weight)  3.52  −3.05, 10.09  0.29  4.42  0.79, 8.05  0.02  Time-point*   T0  Ref             T1  28.82  23.17, 34.47  <0.001  28.81  23.17, 34.47  <0.001   T2  51.85  44.71, 59.00  <0.001  51.85  44.71, 59.00  <0.001   T3  27.58  20.22, 34.94  <0.001  27.58  20.22, 34.94  <0.001   T4  −5.95  −11.60, −0.29  0.04  −5.95  −11.60, −0.29  0.04  Age (per year increase)        0.77  −0.25, 1.78  0.14  Gender (Ref: male)        1.96  −1.78, 5.70  0.30  Crowding (per mm increase)        −0.46  −1.26, 0.35  0.27  Tooth extraction (Ref: non-extraction)        −2.62  −6.58, 1.34  0.19  Baseline pain (per VAS mm increase)        0.43  0.34, 0.52  <0.001  Use of oral analgesia (Ref: no)        4.34  0.02, 8.67  0.05  Plaque index at T0        −5.36  −13.35, 2.63  0.19  Gingival index at T0        2.69  −2.82, 8.20  0.34  *Interaction of obesity with time found to be non-significant (P = 0.42) and was dropped from the model. View Large Analysis of the consumption of oral analgesics (as a binary outcome) revealed no statistically significant association in either the univariable or the multivariable (adjusted) analyses (Supplementary Table S1). Analysis of the total amount of analgesics consumed (as a continuous outcome) revealed statistically significant associations with obesity for both univariable and multivariable (adjusted) analyses (+601.20 mg, P = 0.035 and +646.38 mg, P = 0.023, respectively). There was also a significant association with age in the multivariable analysis, with older patients taking smaller amounts of analgesics (P = 0.018; Supplementary Table S2). After accounting for confounders, obese patients were associated with higher odds of taking analgesics (OR = 1.92) as well as a higher overall amount of consumed oral analgesics (difference = 648.38 mg), although only the latter was statistically significant. Subgroup analysis by gender Subgroup analyses by gender indicated that pain differences between obese and non-obese subjects related mostly to males rather than females, which was true for both maximum pain across time-points (Supplementary Table S3) and mean pain at each time-point (Supplementary Table S4). However, these differences between males and females were not consistently significant (see interaction terms). Additionally, caution is warranted with the interpretation of this subgroup analysis, due to its post hoc nature and the fact that this analysis further diminishes the statistical power of this study. Agreement/reliability of the method Agreement between repeated VAS measurements was found to be very good with an average difference of −0.86, with 95 per cent limits of agreement of −6.14 to 4.42 mm, and no signs of systematic effects (Supplementary Figure S1a). The reliability of the method was likewise very good, with a concordance correlation coefficient of 0.995 and 95% CI of 0.994 to 0.996 (Supplementary Figure S1b). Discussion The commonality of obesity in Western society means that the implications of this condition are likely to affect increasing areas of modern health care and therefore, it is important that clinicians from all specialties understand potential issues associated with the care of obese patients. In the present study, we have investigated orthodontic pain during the first week following the placement of fixed orthodontic appliances in normal-weight and obese children. We found that maximum reported pain across the observation period was not significantly different between the two groups. However, mean maximum pain was higher in the obese group when compared to normal-weight patients at all individual time-points. This general trend for higher pain at each time point and the fact that obesity did not have a modifying effect on the progression of pain through the alignment phase (interaction P > 0.05) suggests that obese patients experienced generally higher pain levels than normal-weight patients. In addition, total analgesia taken by the obese group was also significantly higher than in the normal-weight cohort. These data suggest that obese patients may be more susceptible to orthodontic pain during the first week of treatment with fixed appliances and that orthodontists should take this into account during treatment of this patient group. We found a pattern of orofacial pain intensity during this first week following placement of fixed-appliances similar to that seen in previous investigations (12, 15, 16). This reinforces the consistency of pain response that is observed following placement of fixed orthodontic appliances and makes this a useful experimental model to investigate orofacial pain (12, 15, 16, 18). The prospective design (30) and comparability of the experimental groups at baseline can also be considered strengths of the present study. Moreover, obesity was defined according to widely accepted and reliable measures, which makes misclassification unlikely. Additionally, as the patients in the obese and normal-weight groups were similar apart from their BMI, no drop-outs were seen and VAS measurement blinding was implemented, the respective risk for selection, attrition, and detection bias is low. This is part of a larger prospective investigation of orthodontic treatment response in normal-weight and obese subjects, with a primary sample size calculation based upon rate of orthodontic tooth alignment (31). However, post hoc analysis indicated that this study had 96 per cent power to identify the specified effect on the outcome of maximum-pain experience. Although we did not investigate orthodontic pain in the longer-term, there is evidence to indicate that there is consistency in the pattern during subsequent archwire changes (12, 15, 16). The relationship between obesity and oral disease is complex, but associations with reduced tooth number and irregular dental visits (32), periodontal disease (33–35), and dental caries status (36) have all been described. Moreover, the presence of oral disease seems to have a greater negative impact on quality-of-life in the morbidly obese when compared to normal-weight subjects (37). Although the implications of obesity for orthodontic therapy are less clear, a number of potential associated factors have been discussed that may impact on treatment, which include psychosocial well-being, altered craniofacial growth, overall tissue turnover, and bone metabolism (38–41). The results of this investigation suggest that there are differences in the pain response between obese and normal-weight subjects during orthodontic treatment over the short-term with corresponding differences in the consumption of analgesics. This is in agreement with previous studies, which report that obesity can influence peripheral pain perception and be a contributory factor for increased pain thresholds (5–8). Possible explanations for this relationship include amongst others, peripheral factors such as skin thickness and innervation density, (42) a possible nociceptive modulation through leptin (43) or interaction of ghrelin with central opioid mechanisms, which seems to have an anti-nociceptive effect on endogenous opioids (44). In any case, prolonged orthodontic pain has been shown to have potential negative consequences on compliance (45) and treatment completion (46, 47). As oral analgesics are effective in reducing orthodontic pain (48) it would seem prudent for clinicians to ensure that obese patients are provided with the necessary information and measures to ensure appropriate pain relief following the placement of fixed-appliances. It is premature to suggest that obesity is a clear risk factor for more pain with fixed appliances but within the context of evidence linking obesity with poor compliance (49), it invites speculation that this condition might present different challenges for orthodontists. This is the first prospective study to investigate orthodontic pain in association with variation in body weight and provides evidence that informs clinical practice, both in orthodontics and other areas of medicine and dentistry. The results of this study are widely generalizable and applicable to the majority of obese and normal-weight children aged between 12 and 18 years. Conclusions Based on the results of this prospective cohort study on pain experience during alignment in obese and normal-weight children with moderate-to-severe mandibular incisor irregularity, the following can be concluded: The maximum-pain experienced during alignment in obese patients seems to be slightly higher than normal-weight patients, but this is not statistically significant; Obese patients experience statistically higher mean pain than normal-weight patients at each time-point during the first week after appliance placement; and This was accompanied by a corresponding statistically significant higher consumption of pain medication. Supplementary material Supplementary data are available at European Journal of Orthodontics online. Funding This work was supported by the Ministry of Higher Education and Scientific Research of Iraq through an educational scholarship to HS. Conflict of interest None to declare. 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Published: Oct 9, 2017

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