key: cord-1024441-kjk9wvry
authors: Amer, Mohamed E.; ElKadi, Abbadi; Nadim, Mohamed; Sedky, Youssef
title: Effect of low-level laser therapy on condylar growth in children treated with functional appliance: a preliminary study
date: 2022-05-20
journal: Lasers Dent Sci
DOI: 10.1007/s41547-022-00158-x
sha: dbf791f99752a773856d70b0680626e1e251830d
doc_id: 1024441
cord_uid: kjk9wvry

PURPOSE: This study aimed to evaluate the skeletal and dentoalveolar changes achieved by combining low-level laser irradiation applied on the condyle area with twin-block therapy in growing class II malocclusion patients. METHODS: Fourteen patients (9 males, 5 females; mean age, 11.4 ± 2 years) with skeletal class II mandibular deficiency were recruited. They were divided into two groups (G 1: twin-block + low-level laser therapy, G 2: twin-block only). A semiconductor diode laser with a wavelength of 940 nm was applied on the condyle area (100 mW, 2.5 J, 3.9 J/cm(2)). The laser was applied twice a week in the first month and once a week in the second and third months, totalizing 16 sessions. Skeletal, dental, and soft-tissue cephalometric parameters were measured and compared at different treatment points. RESULTS: Mandibular length (Co-Gn) was significantly increased by 3.6 mm in the experiment group (3.16 SD) and 4.3 mm (4.4 SD) in the control group, with no significant difference between groups at every time point (P-value 0.949 at T2). Similarly, a statistically significant positive effect of treatment was found in both groups on ramus height (Co-Go), upper lip to E-Line, SNA angle, ANB angle, and U1/SN angle with no significant difference between groups. CONCLUSION: Based on the results of this preliminary study, low-level laser irradiation with the used parameters seems to have no synergetic impact on the skeletal and dental outcomes of twin-block therapy over 9 months. However, more studies are needed to investigate the effect of low-level laser therapy on condylar growth during functional orthodontic treatment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s41547-022-00158-x.

Class II malocclusion was found to be the second most prevalent malocclusion in mixed and permanent dentitions [1] . The most consistent etiological factor in class II malocclusion is mandibular deficiency. Growing children with underdeveloped mandibles can have severe psychological and social impacts. It also can lead to life-threatening complications due to severe airway constriction, as seen in nonpositional obstructive sleep apnea [2] .

A therapy able to enhance mandibular growth is indicated in these patients. A variety of functional appliances aimed to stimulate mandibular growth by forward posturing the mandible is available to correct this skeletal and occlusal disharmony. The mandibular condyles have a significant role in the development and growth of the mandible. Accordingly, deficient growth of the condyles may result in mandibular retrognathia. One of the significant roles of functional appliances during the mandibular advancement process is to increase condylar cellular activity. Such activity is characterized by increasing the thickness of cartilage on the posterior aspect of the condyle, leading to an increase in total mandibular length [3] .

Lasers have gained popularity in most dentistry fields for many years and have recently been widely used in orthodontic practice. Dental lasers can be categorized as soft and hard tissue lasers according to their applicability to tissues. Soft lasers can be used in a nonsurgical mode for biostimulation, rapid wound healing, and pain relief. At the same time, soft lasers can be termed low-level laser therapy (LLLT) [4] .

The LLLT, currently called photobiomodulation therapy (PBMT) due to its photochemical effect, in which light is absorbed, promotes a chemical change known as photobiostimulation, which influences cellular activities, including the release of several growth factors responsible for the formation of epithelial cells, fibroblasts, collagen, and vascular proliferation [5] .

Based on the stimulatory effects of the low-level laser therapy and the role of the mandibular condyle in the growth of the mandible, it has been hypothesized that applying lowlevel laser on condyle will stimulate mandibular growth and increase mandibular length subsequently.

This trial was a two parallel-group randomized, blinded controlled trial with a (1:1) allocation ratio. Ethical approval was obtained from the Research Ethics Committee, Faculty of Dentistry, Suez Canal University, Ismailia, Egypt (number 111/2018). The study flow chart is shown in (Fig. 1 ).

Based on the study of Mills et al. [6] , the aid of IBM™ SPSS™ Sample Power™ Version 3.0.1 sample size calculation was achieved. With a total sample size of 14 (7 for each group), the study had the power of 73.6% to yield a statistically significant result. This computation assumes that the mean difference is 1.60 (corresponding to means of 1.90 versus 0.30). The common within-group standard deviation is 1.06 (based on SD estimates of 1.20 and 0.90) for a significance level of 5%.

Participants were recruited from the outpatient clinic, Faculty of Dentistry, Suez Canal University, from 5\2019 to 3\2020. The intervention was carried out by one operator (Mohamed E. Amer). The inclusion criteria were (1) subjects ranging in age between 9.5 to 14 years old, (2) skeletal class II cases where ANB angle is greater than 5° with a mandibular deficiency that the SNB angle is less than 76°, (3) growing patients with cervical vertebrae maturation stage at CS3 or CS4, and (4) subjects should be free from any systemic disease. Patients who had previous orthodontic and/or craniofacial surgical interventions were excluded. 

Twenty patients were included in this study to compensate for dropouts during the study. Patients were equally distributed into laser and non-laser groups (10 patients in each group). Randomization has been done using an excel sheet 1 through the Excel RAND function to assign every patient number in laser group or non-laser group through the following steps. Microsoft Excel sheet was created and used for the randomization process. Then, in the 1st column, numbers from 1 to 20 were written, representing the 20 patients included in this study. In the 2nd column, the laser and non-laser groups were equally assigned for ten numbers each: first ten samples as laser and the next ten as non-laser. In the 3rd column, a randomization formula had been added, which is between 0 and 1. A function called "RAND" had been inserted in the 1st row of the 3rd column. Accordingly, Excel has added a random number to the cell. Random numbers had been added to the entire column. After that, a filter was added to column 2 and column 3 as we wanted to randomize column two. Then, column 3 content has been sorted smallest to largest from the filter function to randomize it. Finally, all the contents in column 2 were randomized, and all patient numbers were randomized to either laser or non-laser groups.

During recruitment of patients, every patient was allocated in a group according to his number in the Excel sheet without concern to the dropouts. After recruiting 20 patients, every group strictly consisted of 7 patients according to the sample size calculation. More than three dropouts in each group were compensated by assigning a patient directly to the incomplete group.

Due to the nature of the intervention, it was impossible to blind the operator during the study because the intervention included applying low-level laser therapy on the condyle by the operator. For this reason, to minimize bias, all cephalometric tracings and measurements were completed by two investigators (M. Salah and A. Kadry), who were blinded to any patient information or group allocation. Moreover, the statistician was also blinded to group allocation.

Lateral cephalograms were obtained for every patient before the beginning of treatment (T0), after 3 months of beginning treatment (T1), and after 9 months from the beginning of treatment (T2). All cephalometric films were taken by the same machine (Sirona ORTHOPHOS XG 5 DS/Ceph). All the cephalometric radiographs were taken in natural head position. The patients were instructed to stand upright and look straight ahead to a point at eye level on a mirror in front of them [7] . Cephalometric tracing was done on the digital cephalogram with Dolphin imaging software version 11.5.04.36 premium.

Cervical vertebrae maturation was assessed to ensure that patients were still at CS3 or CS4 stage. The assessment was done following Baccetti et al. guidelines [8] .

Landmarks used for cephalometric tracing are shown in Table 1 and Fig. 2 . The linear and angular measurements are shown in Table 2 

An alginate impression was taken for every patient on the upper and lower arches. Then, a protrusive construction bite was obtained by softened pink wax. The patients were asked to protrude their mandible and close their mouth trying to get the anterior teeth in edge-to-edge relation. This technique allowed an overjet correction up to 10 mm with a single advancement.

Maxillary and mandibular labial frenums were used as a guide to assure that skeletal midlines were adequately aligned and no mandibular shift during protrusive movement. The patients were instructed to practice opening wide and moving the mandible straight and forward to ensure that the lines on the incisors stay adequately aligned. They were trained on these movements until assured they could do it on wax.

The protrusive construction bite registered the relation between upper and lower arches, and they were mounted on a simple hinge articulator.

The general design of the twin block involved the following:

• Adams clasps on first permanent molars or premolars in both arches (0.7 mm stainless steel) • Ball-ended clasps on the mandibular incisors (0.7 mm stainless steel) • A midline screw placed in the upper block to expand the upper arch • Upper and lower acrylic blocks with inclined planes at 70° to the occlusal plane and at least 5 to 6 mm thick.

• Passive upper labial bow extending from the canine-tocanine tooth (0.7 mm stainless steel).

The twin-block appliance was checked for comfort fit on the delivery appointment, and minor clasps adjustments were made. All the patients were instructed to wear the appliance full time except for eating and brushing. They were also instructed to turn the upper midline expansion screw once a week (0.2 mm) until the necessary transverse expansion was achieved [9] • Laser application protocol

For the laser group, the following protocol was used.

• Laser radiation was done by a semiconductor diode laser near-infrared 940 nm (EPIC X™ by BIOLASE®, USA). The deep tissue handpiece by BIOLASE® was used for laser delivery with a laser beam diameter of 9 mm with an irradiation area of 0.635 cm 2 . • The following laser parameters and settings were used: power (100 mW), irradiation time (25 s), energy (2.5 J), energy density (3.937 J/cm 2 ), in contact mode [10] .

• The points of laser application were marked on the skin according to the method suggested by Laskin [11] . A line was drawn from lateral canthus of the eye to the tragus of the ear, and the point was placed 2 mm below this line and 10 mm forward of the midtragus. • The laser application was done with the twin block in mouth and the patient was asked to close his mouth while upper and lower inclined planes are in touch. • The laser was applied twice a week in the first month and once a week in the second and third months, totalizing 16 sessions [12] . • The device tip was protected with plastic wrap according to the biosafety standards. During the laser application, both the operator and the patient were wearing filter glasses (Fig. 5 ).

Intra-and inter-observer reliability was measured using Cronbach's alpha reliability and intra-class correlation coefficients (ICC). Cronbach's alpha reliability coefficient Cephalometric measurements showed a parametric distribution. Multiple comparisons were achieved with Bonferroni adjustment for linear and angular measurements. Change in cephalometric measurements showed a nonparametric distribution. So, the Mann-Whitney test was used to compare between different groups. The significance level was set at P < 0.05.

Statistical analysis was performed with IBM® SPSS® (SPSS Inc., IBM Corporation, Armonk, NY, USA) Statistics Version 26 for Windows. Angle formed by the intersection of the long axis of the lower central incisor and mandibular plane from gonion to menton Gonial angle

The included angle between articulare, gonion, and menton Y-axis angle Angle formed by the intersection of sella-gnathion line with the Frankfort horizontal plane Frankfurt/mandibular plane angle Angle formed by the intersection of Frankfurt horizontal plane and mandibular plane from gonion to menton 

There was an insignificant difference in cephalometric measurements at the beginning of treatment (T0) between both groups except for the Y-axis angle (FH/S-Gn), which increased significantly in the laser group compared to the non-laser group ( Table 3) .

Different follow-up periods in the laser-treated group showed a significant increase in mandibular length (Co-Gn) and gonial angle (Ar-Go-Me) at T2 compared to the baseline measurement (T0). Also, there was a significant decrease in ANB and U1/SN angles at T2 compared to the baseline measurement (T0) (p > 0.05) ( Table 4 ).

Different follow-up periods in the non-laser-treated group showed a significant increase in mandibular length (Co-Gn) and ramus height (Ar-Go) at T2 compared to the baseline measurement (T0). Also, there was a significant decrease in ANB angle at T2 compared to the baseline measurement (T0) (p > 0.05) ( Table 5 ) (Figs. 3 and 4) .

Insignificant difference between the change from T0 to T1 in laser and non-laser groups for all the cephalometric measurements (p >0.05) except for Frankfurt/mandibular plane angle (Go-Me) angle (Table 6 ).

Insignificant difference between the change from T0 to T2 in laser and non-laser groups for all the cephalometric measurements (p >0.05) ( Table 7) . 

It was found through experimental studies that appliances used to position the mandible anteriorly stimulate significant mandibular growth. This increase is achieved mainly by condylar remodeling [13] and extra elongation in total mandibular length [14] . Twin-block appliance is one of the most commonly used functional appliances clinically because of its excellent results [6, [14] [15] [16] [17] . Low-level laser therapy (LLLT) was found to produce stimulatory effects on fibroblastic and chondral proliferation [5] . Evaluation of the effect of low-level laser therapy on condylar growth has been a point of interest for researchers and clinicians in the last few years. Several experimental studies [18] [19] [20] [21] [22] [23] have shown that low-level laser irradiation can be used for further improvement of mandibular retrognathism. The current study aimed to evaluate the effect of low-level laser therapy on condylar growth in skeletal class II mandibular deficiency patients treated with twin-block appliances.

Choosing the most appropriate wavelength is crucial when using a laser. Laser penetration of the tissues depends mainly on the wavelength. Infrared laser has a low absorption coefficient in hemoglobin and water and a high penetration depth in the irradiated tissue. A wavelength between 780 and 940 nm presents the deepest penetration, reaching the cortical, alveolar bone tissues and, in our case, able to reach the mandibular condyle. On the other hand, red laser (620 and 670 nm) has weaker penetration, mainly due to the high absorption tendency by the biological tissue; it is therefore indicated for superficial lesions, such as tissue repair (healing and local drainage) [24] . A semiconductor diode laser nearinfrared with a wavelength 940 nm was used in the current study. This wavelength was also used in previous experimental studies [25, 26] and clinical studies [10, 27, 28] Low-level laser therapy effects depend on the total amount of irradiation, frequency, and duration of application. There is a dose-related response; at relatively low doses of laser radiation, there can be photobiostimulation which could be helpful in healing enhancement. On the other hand, at higher levels of laser radiation, photobioinhibition occurs, optimal for pain relief [29] . Laakso et al. [30] recommended that the therapeutic window of laser doses may exist between energy densities of 0.5 J/ cm 2 and 4 J/cm 2 . They recommended that doses above these may result in bio-inhibition.

Moreover, Kubasova et al. [31] stated that the saturation of cells towards the biostimulative effects induced by polarized light occurring is at 4 J/cm 2 . Cells cannot absorb any more energy above this level. According to these findings, the energy density used in the study was 3.9 J/cm 2 which was calculated from the given parameters: energy density = energy (J) 2.5 J/area (cm 2 ) 0.635 cm 2 . These parameters were used by Sedky et al. [10] . Furthermore, they found a positive effect of low-level laser therapy on RANKL level and bone remodeling during orthodontic tooth movement.

It has reported that the optimum treatment timing for twin-block therapy of class II malocclusion appears to be during or slightly after the onset of the pubertal peak of mandibular growth (between CS3 and CS4) [14, 32] . In the current study, we recruited growing patients aged 9.5 to 14 years old with cervical vertebrae maturation stage at CS3 or CS4. Skeletal age assessment was performed via evaluation of the cervical vertebral maturation method, following the technique of Baccetti et al. [8] . The advantage of this version is that the skeletal maturity can be evaluated on a lateral cephalogram. The cervical vertebrae maturation method analyzes only the second, third, and fourth cervical vertebrae and comprises six maturational stages (CS1 to CS6).

The most common method to analyze mandibular length in the clinic is the lateral cephalogram. Linear measurements of mandibular length have been observed to have high reproducibility between different measurement times. They are not dependent on whether the patient is positioned in habitual occlusion or centric relation. Skeletal effects of functional treatment seen at the mandibular level consist mainly of increasing mandibular length and ramus height [32] . However, other studies recommended that linear measurements are susceptible to magnification bias [17] . Accordingly, linear and angular cephalometric measurements were used to analyze and compare the treatment groups of the current study.

In the current study, an improvement in mandibular retrognathism was achieved in all the patients. These results were presented clinically by improving the facial profile and statistically by skeletal and dentoalveolar changes. A significant change in the ANB angle and overjet (< 0.001) was seen in all cases, explaining the tremendous change in the facial profile in all treated subjects. Although most studies that examined the effect of twin-block therapy found the same results, the difference between these studies explained how this took place. Several studies attributed these changes to skeletal or dentoalveolar changes or combinations.

Regarding the skeletal effect of twin-block therapy on the mandible, we found an increase in the effective mandibular length (Co-Gn) and ramus height (Ar-Go) in both laser and non-laser groups in the current study. These are desirable outcomes of treatment with functional therapy, and these results are in accordance with Sharma et al. [33] , Saikoski et al. [34] , and the systematic review by Ehsani et al. [15] . After 9 months of twin-block therapy, the mean increase in the mandibular length (Co-Gn) was 3.7 mm in the laser group and 4.3 mm in the non-laser group.

Moreover, regarding the skeletal effect of twin-block therapy on the maxilla, controversial outcomes are reported for the restraining effect on the maxilla. In the current study, maxillary forward growth restriction could be explained by the twin-block's distal reciprocal force exerted on the maxilla (headgear effect). These results were also emphasized by Elfeky et al. [16] and Sharma et al. [33] . However, the current findings are incompatible with those of Saikoski et al. [34] .

Regarding the dentoalveolar effect of the twin-block therapy, there was a significant decrease in the inclination of the maxillary incisors in the current study. Again, this could be attributed to the headgear effect of the incorporated labial arch in the twin-block appliance. These resulted in palatal tipping of the maxillary incisors by 5.5° at the end of treatment. On the other hand, no significant effect was found on mandibular incisors' inclination. These dentoalveolar findings were in accordance with studies reported by Koretsi et al. [17] and Trenouth et al. [16] , who stated that removable functional appliances caused significant dentoalveolar changes (predominantly retroclination of the upper incisors). Nevertheless, Ehsani et al. [15] found consistent reports of proclination of lower incisors and retroclination of upper incisors with twin-block therapy in their systematic review.

So, from our results, the changes following twin-block therapy are a net result of skeletal and dentoalveolar changes. This finding is in accordance with Elfeky et al. [16] and Sharma et al. [33] . On the other hand, O'Brien et al. [35] stated that most of the correction was due to dentoalveolar change.

Consequently, the current results recommended no significant difference between laser and non-laser groups regarding mandibular growth in class II mandibular deficiency patients treated with the twin-block appliance. The current study results comply with Mohamed et al.'s (2020) [36] clinical study. They found that low-level laser therapy has no considerable effect on mandibular condylar volume and position following the twin-block functional orthopedic treatment of skeletal class II malocclusions. On the other hand, several experimental studies have shown that low-level laser irradiation can further improve mandibular retrognathism [18] [19] [20] [21] [22] [23] . This conflict in results between clinical and experimental studies recommends that low-level laser therapy could effectively stimulates mandibular growth but with different parameters than used in the current study.

The results reported in this study should be considered in the light of some limitations. The first limitation is the relatively small sample size. However, our approach was relatively new in the orthodontic practice, including applying low-level laser therapy on condyles of growing subjects. So, our ethical committee limited the recruitment of our sample in the low-level laser group. Moreover, the evaluation was on a short-term basis. However, it was hard for us to accomplish a longer term investigation due to the high dropout rate of the patients because of the Covid-19 pandemic crisis in the middle of our study.

In this study, randomization was performed as described in the material section to minimize the risk of selection bias, more importantly, to balance potential confounding factors between the two groups (laser vs. non-laser group). Notwithstanding this, patients in the laser group were characterized by a vertical growth pattern evidenced by the Y-axis angle measurements at baseline. The use of stratified randomization would have sabotaged this baseline imbalance. Because changes in the vertical dimension have often been shown to affect the response to the functional appliance therapy, this may have confounded the results by showing a significant difference between the two groups regarding the vertical dimension.

From the results of the current preliminary study, it could be concluded that:

1. Low-level laser irradiation with the used parameters seems to have no synergetic impact on the skeletal and dental outcomes of Twin-block therapy over 9 months. 2. Twin-block therapy is effective in growing patients with skeletal class II mandibular deficiency. 3. The changes following twin-block therapy result from skeletal and dentoalveolar changes.

However, more studies are needed to investigate the effect of different low-level laser therapy parameters on condylar growth during functional orthodontic treatment.

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