Tooth Movement, Orofacial Pain, and Leptin, Interleukin-1b, and Tumor Necrosis Factor-A Levels in Obese Adolescents
Tooth Movement, Orofacial Pain, and Leptin, Interleukin-1b, and Tumor Necrosis Factor-A Levels in Obese Adolescents
Tooth Movement, Orofacial Pain, and Leptin, Interleukin-1b, and Tumor Necrosis Factor-A Levels in Obese Adolescents
INTRODUCTION
a
Postgraduate Student, Department of Pediatric Dentistry,
Orthodontics and Public Health, Bauru School of Dentistry, Obesity and its associated comorbidities are in-
University of São Paulo, Bauru, São Paulo, Brazil. creasingly prevalent among adolescents. Childhood
b
Postgraduate Student, Department of Prosthodontics and
Periodontology, Bauru School of Dentistry, University of São and adolescent obesity are associated with health
Paulo, Bauru, São Paulo, Brazil. consequences later in life, including adult overweight/
c
Professor, Department of Orthodontics, Bauru School of obesity1 and cardiovascular, musculoskeletal, and
Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
d
Associate Professor, Department of Pediatric Dentistry, endocrine diseases.2
Orthodontics and Public Health, Bauru School of Dentistry, Patients with obesity suffer from chronic inflamma-
University of São Paulo, Bauru, São Paulo, Brazil. tion accompanied by elevated inflammatory cytokines,
Corresponding author: Silvia Helena de Carvalho Sales
suggesting that these individuals display a dysfunc-
Peres, Department of Pediatric Dentistry, Orthodontics and
Public Health, Bauru Dental School, University of São Paulo, tional immune response. Elevated inflammatory cyto-
Alameda Octávio Pinheiro Brisolla, 9-75, Bauru, SP 17012-901, kines interleukin (IL)–1b, IL-6, and tumor necrosis
Brazil. factor (TNF)–a are primarily produced by an increased
(e-mail: shcperes@usp.br)
number of macrophages in obese adipose tissue, and
Accepted: May 2021. Submitted: January 2021.
Published Online: August 2, 2021
their altered circulating levels have been reported in
Ó 2022 by The EH Angle Education and Research Foundation, patients with obesity, contributing to local as well as
Inc. systemic chronic inflammation.3
Encountering obese patients who undergo ortho- treated with antibiotics in the past 6 months, smoker,
dontic treatment is becoming more common, as the and pregnant or breast-feeding.
incidence of individuals who are obese and overweight
is increasing worldwide.4 The effect of oral habits on Anthropometric Evaluation
cranial and maxillofacial growth and development is
Measurements of body mass and body composition
dependent on the nature, onset, and duration of the
were performed using Inbody 230 Multifrequency
habits. Orofacial pain may negatively affect adoles-
Tetrapolar Bioimpedanciometer (Biospace, Rio de
cents. Widespread pain may indicate changes related
to central sensitization, partially explaining the rela- Janeiro, Brazil), with 100 g of precision and a
tionship between obesity and comorbidities with painful maximum capacity of 250 kg.9 Height was measured
conditions.5 using a stadiometer attached to the wall with an
contact points must be moved to achieve alignment12 reading of the plates by MagPix equipment (Luminex
and was used in this study indirectly to measure the Corporation, Austin, Tex), following the protocol
amount of tooth movement in the groups. Similar indicated by the manufacturer.
intergroup changes in the index would indicate similar Mann-Whitney and t-tests were used for intergroup
amounts of tooth movement. comparisons, and a generalized estimating equation
and cluster analyses were used for interphase com-
VAS for Orofacial Pain parisons (P , .05).
Pain sensitivity was evaluated after 1 hour, 24 hours,
and 1 week of fixed appliance bonding (T1, T2, T3) using RESULTS
a VAS in which the patient scored the intensity of pain
The obese group (G1) showed significantly higher
experienced from 0 to 10.13 The volunteers were
values for weight, BMI, waist-to-hip ratio, fat mass, and
instructed not to use any analgesic medications within
percentage body fat as compared with the controls
1 week of fixed appliance bonding.
(G2; Table 1). The participants were stratified accord-
GCF Collection ing to their periodontal status. G1 had a significantly
smaller percentage of 0- to 3-mm probing depths and a
GCF was collected with sterile absorbent paper significantly greater percentage of 4- to 5-mm probing
cones. For collection, supragingival plaque removal depths and bleeding sites than G2 did (Table 2).
was performed, followed by isolation with cotton rolls Crowding was similar in the groups, both initially and
and drying with an air syringe for 5 seconds. After
after 1 week of treatment (Table 3). There were
preparation, absorbent paper cones (#30, Tanari, AM,
significant decreases in crowding after 1 week of
Brazil) were inserted into the gingival sulcus at a 1 mm
treatment in both groups.
depth for 30 seconds, distal to the six mandibular
anterior teeth (central and lateral incisors, and canine). Pain intensity was greater at all time points for the
If the paper ends were contaminated with blood or obese group; however, the difference between groups
saliva, they were discarded. was significant only at T2 (Table 4).
Immediately after collection, the paper cones were The obese group had significantly higher concentra-
transferred to Eppendorf tubes containing 200 lL of tions of IL-1b cytokine than the control group did. The
buffered saline (phosphate-buffered saline) with 0.1% concentration varied significantly with time (Table 5).
Tween 20 solution (USB Corp, Cleveland, Ohio) and 1 TNF-a cytokine varied significantly with time.
lL of protease inhibitor cocktail (Sigma-Aldrich, St
Louis, Mo). The tubes were shaken for 30 minutes and Table 2. Periodontal Parameters by Groupa
centrifuged at 10,000 rpm for 5 minutes and then G1 (n ¼ 30) G2 (n ¼ 30)
stored at 808C for further laboratory analysis. Obese Eutrophic P
PD, mm 2.13 6 0.34 2.07 6 0.25 .39
Laboratory Stage PD 0–3 mm, % sites 97.44 6 4.35 98.05 6 3.45 .00*
PD 4–5 mm, % sites 0.53 6 1.00 0.21 6 0.52 .00*
Evaluation of IL-1b, TNF-a, and leptin in the GCF % Calculus, teeth 7.97 6 8.64 5.90 6 6.78 .48
was performed using Luminex xMAP for multiple % BOP, sites 11.27 6 5.92 6.50 6 3.76 .00*
assays, using the appropriate kit (Cat. No. HADK2- a
BOP indicates bleeding on probing; PD, probing depth.
MAG-61K, Millipore Corporation, Billerica, Mass), with * Statistically significant at P , .05.
Table 3. Little’s Irregularity Index: Initial (T0) and After 1 wk of Orthodontic Treatment (T3)
T0 T3 Group Time Group 3 Time
Dental crowding, mm
G1 4.90a (4.01–5.79) 3.50b (2.67–4.33) .43 .00* .72
G2 4.50a (3.75–5.25) 3.03b (2.38–3.68)
a,b
Indicates statistically significant differences
* Statistically significant at P , .05.
Table 5. Comparisons of Leptin, IL-1b, and TNF-a Cytokine Concentrations Over Time, Within and Between Groups
T0 T1 T2 T3 Group Time Group 3 Time
Leptin, pg/mL
G1 14.9 (10.6–19.2) 14.8 (11.5–18.0) 12.0 (11.4–12.5) 13.0 (11.5–14.4) .08 .30 .41
G2 11.9 (11.3–12.4) 11.8 (11.4–12.0) 11.5 (11.3–11.7) 11.7 (11.4–12.0)
IL-1b, pg/mL
G1 10.3 (5.0–15.6) 12.8 (6.9–18.7) 20.1 (12.4–27.7) 17.9 (7.5–28.2) .01* .00* .61
G2 4.47 (2.9–6.0) 3.4 (1.7–5.0) 11.5 (3.9–19.0) 12.2 (5.6–18.8)
TNF-a, pg/mL
G1 0.47 (0.29–0.65) 0.90 (0.73–1.07) 0.80 (0.55–1.05) 0.40 (0.15–0.65) .28 .00* .34
G2 0.37 (0.19–0.54) 0.63 (0.44–0.83) 0.60 (0.33–0.87) 0.50 (0.26–0.74)
There were decreases in leptin concentrations in supports the role of inflammation in initial tooth
relation to baseline at T1 and T2, with a slight increase movement.30 On the other hand, leptin levels de-
at T3 in both groups. A decrease IN leptin concentration creased in the first week. The hypothesis would be
in the GCF after 1 hour and 24 hours after bonding of that this was caused by leptin’s inhibition of bone
fixed appliances suggested that leptin may be one of resorption, which is desirable at the beginning of tooth
the mediators responsible for tooth movement.26 movement.
The decrease in leptin levels at the beginning of Despite the limitations of this investigation, the
tooth movement might possibly be explained by the results contribute to the scientific literature, since there
fact that leptin inhibits genesis and action of osteo- are few studies associating excess weight, pain, and
clasts.27 This decrease in GCF leptin concentration orthodontic tooth movement. The relationship between
might be consequent to tissue resorption in the obesity and orthodontic treatment, especially in relation
compressed and tension sites or even secondary to to tooth movement, remains unexplained because of
possible cell necrosis in the periodontal ligament the scarcity of studies in this area. Therefore, clinical
during orthodontic treatment.28 protocols should not yet be changed, and tooth
The correlation between salivary leptin and the slow resorption should not be considered to be associated
tooth movement rate in obese individuals was present- with obesity, as scientific data are insufficient.
ed previously.29 However, the current results demon-
strated that the tooth movement was similar in both CONCLUSIONS
groups (Table 3). The obese group had the highest
concentration of IL-1b cytokine 24 hours after bonding, Obese adolescents displayed higher orofacial pain
while this occurred at 7 days in the control group. after 24 hours of orthodontic treatment and higher
According to a systematic review,7 the IL-1b cytokine concentrations of IL-1b proinflammatory cytokine
level peaked after 24 hours. On the other hand, before and during tooth movement than nonobese
another study reported that the peak was reached in adolescents did.
7 days.30 However, IL-1b is one of the chemical There was no difference in tooth movement between
inflammatory mediators that induces secretion of obese and nonobese patients during the first week of
substances that cause pain.31 This fact can be orthodontic treatment.
confirmed by the intergroup difference in the levels of
cytokine and pain since obese individuals in the ACKNOWLEDGMENTS
present study reported peak pain after 24 hours,
coinciding with the peak concentration of IL-1b. This work was supported by the São Paulo Research
Foundation (FAPESP grant 2018/25934-0) and the
In both groups, there was an increase in the
Coordination of Superior Level Staff Improvement (CAPES
concentration of TNF-a cytokine at T1 and T2 in relation
financial code 001).
to baseline, with a decline at T3. This behavior followed
the pattern described in a systematic review,8 in which
DISCLOSURE
all evaluated studies showed an increase in the first 24
hours after bonding of fixed appliances, with a decline The authors declare no conflict of interest.
after 1 week. As was found in the current study, the
application of orthodontic forces caused an immediate REFERENCES
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