This split-mouth trial aimed to investigate the effect of low-level laser therapy (LLLT) on the amount of maxillary canine distalization when applied every 4 weeks over 12 weeks.
Twenty-two adolescents and young adults (15 female, 7 male; aged 13-25 years; n = 22) requiring bilateral maxillary first premolar extractions were recruited. After extractions and leveling-alignment, canines were retracted using closed-coil nickel-titanium springs delivering 150 g of force. LLLT was applied to 8 intraoral points on the buccal and palatal sides around the canine root for 10 seconds per point, on day 0, 28, and 56 with the control side receiving sham application. Alginate impressions were taken every 4 weeks on day 0, 28, 56, and 84. The amount of tooth movement, anchorage loss, and canine rotation were measured digitally. Randomization was generated using www.randomisation.com and allocation concealment through sequentially numbered, opaque, sealed envelopes. Participants, operator, and statistic assessor were blinded. Linear regression modeling accounting for clustering within each patient was used to identify differences between LLLT and control sides.
Twenty-one patients completed the study. The total amount of tooth movement was similar in the LLLT (2.55 ± 0.73 mm) and control group (2.30 ± 0.86 mm), whereas 0.25 mm (95% confidence interval, –0.21, 0.71 mm) of difference was insignificant ( P = 0.27). No significant differences were found for anchorage loss ( P = 0.22) or canine rotation ( P = 0.25). No harms were reported.
Application of LLLT every 4 weeks did not result in differences in the amount of tooth movement, anchorage loss, and canine rotation during extraction space closure.
Canine distalization was compared between LLLT and control sides.
The amount of tooth movement was similar in the LLLT and control sides.
No differences were found in anchorage loss and canine rotation between the 2 sides.
LLLT did not influence the amount of orthodontic tooth movement when applied every 4 weeks.
There are increasing demands from the patient and clinician perspective to reduce the length of orthodontic treatment time. Methods of accelerating orthodontic tooth movement (OTM) have been investigated not only to satisfy patient and clinician demands, but to decrease the risk of iatrogenic side effects such as root resorption, pain, discomfort, dental caries and to improve compliance.
The rate at which a tooth moves following application of orthodontic force is largely limited by the biological processes involved with alveolar bone and periodontal ligament (PDL) remodeling. Externally applied orthodontic force stimulates both pathological (minor reversible injury) and physiological reactions in the periodontal tissues via creation of areas of pressure and tension within the PDL. This effect alters the PDL blood flow, stimulating the synthesis and release of key molecules, which recruit and activate osteoclasts and osteoblasts to remodel the PDL, thus resulting in OTM. , The response of the periodontium to OTM varies with biomechanical signals as well as host factors such as occlusion, metabolism, age, and variation in bone form and density. One group of signaling molecules is receptor activator of nuclear factor-kappa B ligand (RANKL), a protein found on osteoblast membranes, and its receptor activator nuclear factor-kappa B (RANK), located on osteoclast precursors. Communication between RANKL and RANK leads to osteoclast formation and activation. Osteoprotegerin (OPG) is also released by osteoblasts and fibroblasts within the PDL and controls osteoclastogenesis by inhibiting the RANK/RANKL binding. ,
Procedures to accelerate OTM can involve biological, mechanical, and surgical interventions aimed at enhancing these biological processes. A recent survey of orthodontists, patients, and parents found that less-invasive techniques were more accepted compared to surgical techniques or the use of intraoral drugs. Low-level laser therapy (LLLT) is a noninvasive and nonsurgical technique involving the exposure of cells or tissue to low levels of red and near infrared light (600-1000 nm) to alter cellular function and metabolism. Cytochromophores in mitochondria absorb the laser energy forming adenosine triphosphate (ATP), which, through transcription and protein synthesis results in increased cellular proliferation and cellular activity of target cells. During OTM, LLLT increases PDL turnover by stimulating osteoclast and osteoblast proliferation and enhancing vascularization and organization of collagen fibers. Increased osteoclast and osteoblast proliferation occurs as LLLT augments the RANK/RANKL and OPG pathways. Using a laser probe (808 nm, 100 mW) on a rat model, Suzuki et al observed an increase of osteoclastogenesis and RANKL expression on the compression side and increased bone formation via increased OPG expression on the tension side.
The first human study investigating the effect of LLLT on OTM during canine retraction was by Cruz et al using an aluminum gallium arsenide (GaAlAs) diode (780 nm, 20 mW) applied 4 times a month (on day 0, 3, 7, 14, and 21) for 2 months. The authors observed a statistically significant increase in the rate of tooth movement in the laser group by 34%. Since this study, several studies have found an increased rate of space closure during OTM using lasers in the 720-810 nm range. One study found no effect of LLLT on canine retraction although their protocol and parameters differed with higher energy doses of 18.4 joules (J) per session delivered. Currently, there is low to moderate evidence that LLLT can increase the rate of OTM by up to 30%. Despite these findings, the optimum wavelength, dosage, or power is undetermined. , Studies using a laser with an 810-nm wavelength have shown that there is a potential for increased rates of OTM , , ; however, the protocols of laser application (for example multiple days in a month, the first 3 days of each month or fortnightly application) may not be clinically feasible.
Specific objectives or hypothesis
The primary aim of this study was to investigate the effect of 4-weekly applications of LLLT on the rate of tooth movement when 150 g of distalization forces are applied to maxillary canines over a 12-week period. Secondary outcomes were to determine if there were any differences in anchorage loss or canine rotation from 4-weekly applications of LLLT.
Material and methods
Trial design and any changes after trial commencement
This was a triple-blind randomized controlled clinical trial. The clinician, participants, and researcher performing the statistical analyses were all blinded to the side allocation. It had a 2-arm split-mouth design in which the right side of each patient was randomized to either an experimental LLLT group or sham control group. A split-mouth design was employed to control any potential patient-related confounders such as mouth side, masticatory preference, or individual tooth movement potential, because no contamination of LLLT between mouth sides were expected. There were no alterations after commencement of the trial.
Participants, eligibility criteria, and settings
Ethics approval was granted by Sydney Local Area Health District, Royal Prince Alfred Hospital Zone (ethics approval numbers X16-0276 and Human Research Ethics Committee/16/RPAH/347).
Twenty-two participants (15 females, 7 males) aged between 13 and 25 years (mean age 17.3 ± 2.5 years) were recruited from the orthodontic waiting list at Sydney Dental Hospital. The selected patients required bilateral extraction of maxillary first premolars and canine retraction with moderate anchorage as part of their orthodontic treatment. Eligible patients were (1) healthy with no medical conditions or medications affecting the development or structure of teeth, alveolar bone or rate of tooth movement; (2) in the permanent dentition with no craniofacial and dental anomalies or missing teeth; (3) without any previous dental or orthodontic treatment of the maxillary arch; (4) had no previous orthodontic treatment; (5) had no history of trauma, bruxism or parafunction; and (6) no past or present history of periodontal disease. The patient or guardian obtained verbal and written informed consent (if under 18 years old) and pretreatment records were obtained before commencement of treatment.
Maxillary first premolars were extracted uneventfully except 1 patient who required surgical removal of a premolar root. Patients were then bonded with self-ligating 0.022-in slot SPEED brackets (Hanson prescription; Strite Industries, Cambridge, Ontario, Canada). A standardized wire sequence of 0.014-in or 0.016-in nickel-titanium (NiTi; 3M Unitek, Monrovia, Calif) for 8 weeks, 0.018 × 0.018-in 3t Tritanium Memory wire (American Orthodontics, Sheboygan, Wis) for 8 weeks, and 0.019 × 0.025-in beta-titanium molybdenum (3M Unitek) for 8 weeks was used to achieve leveling and alignment. Anchorage was established using a Nance transpalatal arch from the second molars and reinforced with consolidation of the second premolars, first and second molars using a 0.010-in stainless steel (SS) ligature tie on either side. Canine retraction commenced on an 0.020-in SS wire using medium superelastic NiTi closed-coil springs (Orthomax, TOMY International, Burwood, Australia) attached to 5 mm powerarms (0.016 × 0.016-in SS; Dentarum, Ispringen, Germany) from the canine to the first molar ( Fig 1 ). The NiTi coils were set to deliver 150 g of force, determined using a calibrated spring gauge (Dentarum) and verified at each appointment. Occlusal stops (Transbond Plus Light Cure Band Adhesive; 3M Unitek) were placed on the first molars to prevent any occlusal interference during retraction. Any breakages were rectified within 24 hours, or the patient was excluded from the study.
A GaAlAs diode laser with a mean wavelength of 808 (standard deviation [SD], 5 nm), power of 0.20 W, and irradiance of 1.97 W/cm 2 in continuous wave mode was used (Thor Photomedicine, Buckinghamshire, United Kingdom). LLLT was delivered by applying the laser probe over 8 points per canine tooth (4 on the buccal side, and 4 on the palatal side; Fig 2 ). The laser output was set at 10 seconds per point in continuous mode, which provided 1.72 J of energy per point or a total of 13.87 J per visit. LLLT was applied at commencement of canine retraction on day 0 (T0), 28 (T1), and 56 (T2) immediately after spring activation. Protective goggles were worn, and patients were irradiated in an enclosed room as per laser specifications. The sham laser function did not deliver any energy output; however, it would perform identically to the test laser function, and therefore, the operator and patient were blinded as the wavelength used was not in the visible spectrum.
Outcomes (primary and secondary) and any changes after trial commencement
Alginate impressions (Dentalfarm Australia Proprietary, Sydney, Australia) and clinical measurements using digital calipers were taken on day T0, T1, T2, and T3 (day 84). Impressions were poured up on the same day and the study models from each time point were scanned by a 3D laser scanner (Trios 3; 3Shape A/S, Copenhagen, Denmark) onto 3Shape Orthoanalyzer software (version 22.214.171.124; 3Shape A/S) and analyzed by 1 operator (D.M.).
Tooth movement was determined by measuring the distance between the distal contact point of the canine to the mesial contact point of the second premolar and comparing these distances over the following points: T0-T1, T1-T2, T2-T3, and T0-T3 ( Fig 3 ).
Canine rotation was recorded by measuring the angle between the line created from the mesial and distal contact points of the canine to the midsagittal plane. Anchorage loss was measured by the distance of the second premolar cusp tip to the most medial point of the third palatal rugae. Both secondary outcomes were taken with reference to the occlusal plane, which was set from the most occlusal tip of the second molars to the most incisal tip of the central incisors ( Fig 3 ).
Sample size calculation
Sample size was set according to previously published split-mouth studies investigating a similar research topic and calculating that a sample of 20 patients is required for obtaining a clinically meaningful difference between LLLT and control side of 1 mm with a SD of 0.99 mm with alpha = 0.05 and a power of 80%. ,
Interim analysis and stopping guidelines
Randomization (random number generation, allocation concealment, implementation)
Allocation concealment took place through an enclosed internal laser switch where the laser and sham settings were set by a person (A.K.P.) with details unknown to the operator (D.M.). The switch casing is enclosed so that the switch settings are concealed from the operator. A description of the switch settings was previously published. The internal switch settings of laser and sham were allocated to a letter, A or B, and details placed in sequentially numbered opaque sealed envelopes, which was revealed after data analysis. At the beginning of the retraction period, the right canine tooth from each patient was randomly allocated to letter A or B using randomization software ( www.randomisation.com ) with a 1:1 allocation ratio. The left side of the patient then received the alternate setting.
The laser output wavelength (810 nm) is not visible to the human eye and does not produce heat; therefore, both the patient and the operator were blinded throughout the study. Laser operator also performed the measurements and was blinded to whether A and B corresponded to laser or sham sides of applications. Statistical analysis was performed with the assessor blinded to whether sides A and B corresponded either to LLLT or control sides, and the details were disclosed after supplying the results of the analysis.
Descriptive statistics were calculated, including means and SD for continuous variables and absolute and relative frequencies for categorical variables. Because the right and left side of a patient’s mouth is correlated, multilevel mixed-effects linear regression modeling of change from baseline values for each outcome with robust standard errors was used to account for clustering, and its results were expressed as unstandardized regression coefficients (b) and 95% confidence intervals (CI). Correlations for all absolute values for each outcome were calculated to inform future sample size calculations and meta-analyses. All analyses were run in Stata SE (version 14.0; StataCorp, College Station, TX), and the investigators openly provided the dataset.
All treatment interventions and measurements were taken by a single operator (D.M.). Repeated measurements of 30 randomly selected digital models were taken 30 days after initial measurements to determine the overall standard error of measurement and the coefficient of variation. To examine measurement reliability and agreement, digital casts at different time points were randomly selected and remeasured after 4 weeks. The concordance correlation coefficient and Bland-Altman method were used to test intraexaminer reliability and agreement.
Patient flow through the study is illustrated in the CONSORT diagram ( Fig 4 ). Twenty-one patients completed the study, which included 7 males (33%), 14 females (66%) with a mean age of 17.4 years (SD, 2.6 years; range, 13-23 years). One patient was excluded because of an appliance breakage between T2 and T3 in which the operator was only notified 4 days after the breakage. Patient recruitment started in June 2017 and ended in April 2018. The LLLT and control groups were similar at T0 in extraction spaces (6.54 ± 1.33 mm and 6.09 ± 0.90 mm, respectively), canine rotation (38.96 ± 8.81° and 35.44 ± 7.10°, respectively), and anchorage unit position (6.41 ± 3.50 mm and 6.60 ± 3.01 mm, respectively). Calculations indicated within-person correlations at T3 of 0.55 for contact point measurement, 0.07 for canine rotation, and 0.84 for anchorage loss.
Numbers analyzed for primary outcome and subgroup analysis
The mean amounts of tooth movement at each timepoint are shown in Table I , while the amounts of canine rotation and anchorage loss are given in Tables II and III . Multiple mixed-effects linear regression analysis indicated no significant difference in treatment effects (change from T0) for contact point measurement ( P = 0.36), canine rotation ( P = 0.05), or anchorage loss ( P = 0.20; Table IV ). Furthermore, no significant variation of treatment effects with time was seen, as no statistically significant interaction of treatment with time was found in all cases ( P > 0.05). Significant increases in space closure ( Fig 5 ) and canine rotation ( Fig 6 ) were seen at T2 and T3 compared with T1.