Effect of Low-Level Laser Therapy on Relapse of Rotated Teeth: A Systematic Review of Human and Animal Study

Abstract

Objective and background: Low-level laser therapy (LLLT) has been used to reduce the relapse of orthodontically rotated teeth. However, controversial conclusions have been drawn by different authors. This review aimed to evaluate the efficacy of LLLT on relapse of corrected tooth rotations systematically by overall search of available studies and scientific assessment. Methods: A comprehensive electronic search was performed through PubMed, MEDLINE, EMBASE, Web of Science, CENTRAL, PRL, and WHO ICTRP up to November 2015 with no language limitation. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Risk of bias assessment was undertaken according to Cochrane Handbook for Systematic Reviews of Interventions. Two review authors conducted the work of search, selection, and quality assessment independently in duplicate. Results: Out of 112 studies, two animal experiments and one human study were included. Degree and percentage of relapse of rotated teeth were compared between control and LLLT group. Conclusions: According to the results of our systematic review, the effect of LLLT on relapse of corrected tooth rotations is related to energy density. Namely, low energy density seems to promote relapse, while high energy density might alleviate the relapse. Since available investigations are limited, more well-designed randomized controlled trials involving humans are needed to get more clinically significant conclusions.

Introduction

One important goal of orthodontic treatment is to stabilize the teeth in their new position and reduce their relapse tendency. During orthodontic treatment, the periodontal tissues around the teeth, including gingiva, periodontal membrane, and alveolar bone develop a series of changes under the stimulation of force, so that the teeth can move. These supporting tissues may remain unadapted even though the teeth have been retained in the new place for ages, which may contribute to the relapse and the failure of orthodontic treatment. This occurs especially in cases where the respective teeth have been rotated.

Many studies have researched different methods to reduce the relapse of orthodontically rotated teeth, including gingival injection of relaxin,¹ circumferential supracrestal fiberotomy (CSF),^2

–7 laser-aided CSF,^8,9 gingivectomy,¹⁰ overcorrection, prolonging the use of retention appliances for a considerable period of time,¹¹ reproximation,^5,6 and early correction during the eruption of tooth.¹² These methods could truly decrease the risk of relapse, but they have some drawbacks; for example, they might cause some pain and discomfort to the patients, or surgical procedures used to reduce the relapse might have negative effects on periodontal tissues.

Compared to the aforementioned methods, low-level laser therapy (LLLT) has not reported negative systematic effects on human beings yet. Since its first introduction into clinical medicine in 1968,¹³ there are lots of published data on the use of LLLT because of its noninvasive manner and biostimulatory effect on tissues without increasing the temperature of treated region above the normal body temperature. This technology is also widely used in stomatology, such as enhancement of the stability of orthodontic mini-implants,¹⁴ reducing pain and inconvenience for patients with orthodontic adjustment^15,16 or recurrent aphthous stomatitis,¹⁷ prevention of dental caries,¹⁸ improvement of enamel surface microhardness around orthodontic brackets,¹⁹ relieving dentine hypersensitivity,²⁰ accelerating tooth movement during orthodontic treatment,²¹ and so on.

Researches have been conducted to confirm the effectiveness of LLLT on the relapse of rotational teeth, including animal models and human subjects. Therefore, a systematic review of available knowledge is in need to comprehensively evaluate the influence of LLLT on the relapse of orthodontically rotated tooth.

Materials and Methods

This systematic review was carried out and reported in accordance with Cochrane Handbook for Systematic Review of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently conducted search and the work of extracting data, and assessed the risk of bias and eligibilities of the retrieved articles. Any disagreement was resolved by discussing with a third reviewer.

Search strategy

The following databases were searched: PubMed, MEDLINE (via OVID), EMBASE, Web of Science, website of Cochrane Central Register of Controlled Trials (CENTRAL), and ProQuest Research Library (PRL). Ongoing clinical trials were searched in World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). Terms used in the search included “laser therapy, low-level/laser therapy/laser irradiation/laser,” “orthodontics/orthodontic,” “relapse.” Specifically, the electronic searching was conducted up to November 2015 with no language restriction. Table 1 shows strategies used in the data search process. This process was conducted independently and in duplicate by two reviewer authors.

Table 1.

Search Strategies for Different Databases

Database	Search strategies
PubMed	(laser therapy, low-level [mesh] OR laser therapy OR laser irradiation OR laser) AND (Orthodontics [mesh] OR orthodontic) AND relapse
MEDLINE (via OVID)	(laser therapy, low-level OR laser therapy OR laser irradiation OR laser) AND (Orthodontics OR orthodontic) AND relapse
EMBASE	(laser therapy, low-level OR laser therapy OR laser irradiation OR laser) AND (Orthodontics OR orthodontic) AND relapse
Web of Science	(laser therapy, low-level OR laser therapy OR laser irradiation OR laser) AND (Orthodontics OR orthodontic) AND relapse
CENTRAL	(laser therapy, low-level OR laser therapy OR laser irradiation OR laser) AND (Orthodontics OR orthodontic) AND relapse
PRL	(laser therapy, low-level OR laser therapy OR laser irradiation OR laser) AND (Orthodontics OR orthodontic) AND relapse
WHO ICTRP	orthodontics

Inclusion criteria

Types of studies

We included studies that estimated the efficacy of LLLT on the relapse of orthodontically rotated tooth. The study design should be randomized controlled trials (RCTs), quasi-RCTs, or controlled clinical trials (CCTs).

Types of experimental subjects

Subjects included in this review could be animals or human beings. For the former, experimenters should comply with the principles of animal rights defined by authorities. For the latter, the studies should have been approved by the appropriate research ethics committee. Moreover, the participants should have no systematic diseases, should have exhibited good oral hygiene, and should have agreed to attend this research.

Exclusion criteria

Types of studies

Reviews, case reports, cohort studies, descriptive studies, letters, opinion articles, and abstracts are excluded.

Types of experimental subjects

Patients with gingival or periodontal problems and those who consumed medicine that interrupted bone metabolism are excluded.

Study inclusion

Two reviewers independently conducted the search, reviewed the titles and abstracts, and went over the full text when information given by the abstracts was insufficient to judge whether the articles met the inclusion criteria or not. Also, they discussed with a third reviewer when there was a disagreement.

Assessment of risk of bias

Risk of bias assessment was undertaken according to Cochrane Handbook for Systematic Reviews of Interventions. The features of interest in the standard “Risk of bias” table of Cochrane review were as follows: sequence generation (selection bias), allocation sequence concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), selective outcome (reporting bias), and other potential sources of bias. Each entry of these features addressed a specific feature of the included studies. The judgment for each entry involves assessing the risk of bias as “low risk,” as “high risk,” or as “unclear risk,” with the last category indicating either lack of information or uncertainty over the potential for bias.

Data extraction

Basic data of the included studies were extracted and recorded independently and in duplicate by two review authors, including study design, participant information, methods used to rotate the teeth, interventions for each group, time for rotation and follow-up, retention or not, means to measure tooth movement, and the final conclusions. Meanwhile, the parameters of LLLT were recorded in the same way, including type of laser, wavelength, energy density, power output, energy during each irradiation session, spot area, spot size, and frequency of laser treatment. Further, the degree of initial rotation and relapse, and percentage of relapse were also extracted. Last, information relating to feasible adverse effects caused by LLLT on experimental subjects and histologic examination was also extracted.

Results

Search results

A total of 112 studies were collected following the search strategies mentioned earlier. After screening the titles, abstracts, and full texts when necessary, three articles met the inclusion and exclusion criteria and were brought into the systematic review. The procedures of electronic searching are presented in Fig. 1.

FIG. 1.

Systematic search and selection strategy (flow chart).

Characteristics of included studies

Three studies were included in this systematic review: two animal experiments, conducted on mandibular lateral incisors in beagles, and one human study that included 23 rotated maxillary incisors. Table 2 elucidates the general characteristics of the recruited studies. Meanwhile, details of laser parameters used in every study are summarized in Table 3.

Table 2.

General Information of Recruited Studies

Study ID	Study design	Participants/age or weight (animal study)	n (I/C)	Method to rotate teeth	Intervention and control group	Time for rotation	Follow-up	Tooth movement measurement	Outcome
Kim et al.⁹	Animal study, beagles	12–18 months/10–13 kg	6/6	Rotate the mandibular lateral incisors with rotational couple forces caused by elastic chains, each of which exerted forces of around 50 gm	I: LLLT after removing the orthodontic appliance C: orthodontic couple force application only	4 weeks, change elastics once a week	No retention, 1 month for the teeth to relapse	Measurement of dental casts with computer image analyzer	LLLT will increase the relapse tendency
				Labial surface: canines used as anchorage
				Lingual surface: experimental lateral incisors used as reciprocal anchorage
Jahanbin et al.⁸	RCT, human maxillary incisors	12 patients/ 16–32 years	12/11	Orthodontic therapy to treat the rotational maxillary incisors, no specified methods mentioned	I: laser irradiation on maxillary central incisors during relapse for LLLT group	Not mentioned	No retention, 1 month for the teeth to relapse	Measurement of dental casts with computer image analyzer	LLLT can alleviate relapse
					C: no intervention for control group
Salehi et al.²²	Animal study, beagles: split-mouth design	12–18 months/18–24 kg	8/8	Rotate the mandibular lateral incisors with rotational couple forces caused by elastic chain (50 g)	Laser irradiation on mandibular left lateral incisors during orthodontic force application, no irradiation on the right side (with orthodontic couple force application only)	4 weeks, change elastics once a week	No retention, 3 months for the teeth to relapse	Measurement of dental casts with computer image analyzer	LLLT can alleviate relapse
				Labial surface: canines used as anchorage
				Lingual surface: central incisors used as anchorage

C, control group; I, LLLT group; LLLT, low-level laser therapy; n, number of subjects; RCT, randomized controlled trials.

Table 3.

Details of Laser Parameter

Study ID	Type of laser	Wave-length (nm)	Energy density (J/cm²)	Power output (mW)	Duration of each treatment session for one tooth(s)	Spot area	Spot size	Frequency of laser treatment
Kim et al.⁹	Gallium-aluminum-arsenide diode laser pulsed wave	808	4.63–6.47	763	240	8 regions around the tooth, including the coronal and apical thirds of the mesiobuccal, distobuccal, mesiolingual, and distolingual sides of the roots: laser held 2–3 mm away from the gingiva	0.4 mm in diameter	Every 3 days for 4 weeks
Jahanbin et al.⁸	Gallium-aluminum-arsenide diode laser continuous wavelength	810	35.7	200	200	4 points around the tooth, including mesiobuccal, distobuccal, mesiolingual, and distolingual areas: laser probe positioned in contact with gingival tissue in the coronal third of the root	0.28cm²	Twice a week for 4 weeks
Salehi et al.²²	Gallium-aluminum-arsenide diode laser continuous wavelength	810	31.8	200	10	2 points at the buccal side of the root of the mandibular left lateral incisor: between the cervical third and the middle third, and between the middle third and the apical third	2 mm in diameter	Days 0, 1, 2, 3, 4, 7, 14, 21, and 28 during rotation

Methodological and quality assessment

Randomization was performed among all included RCTs. One animal experiment²² used split-mouth design and took the left side as the experimental group. And no withdraws happened in the CCT.⁸ Risk of bias assessment according to the Cochrane Handbook for Systematic Reviews of Interventions for each study is presented in Table 4.

Table 4.

Quality Assessment of the Included Studies

Studies	Random sequence generation	Allocation concealment	Blinding of participants and personnel	Blinding of outcome assessment	Incomplete outcome data	Selective reporting	Other bias
Kim et al.⁹	?	+	?	+	+	+	+
Jahanbin et al.⁸	+	−	?	+	+	+	+
Salehi et al.²²	?	+	?	+	+	+	+

+, low risk of bias; −, high risk of bias; ?, unclear risk of bias.

The effect of LLLT on relapse of orthodontically rotated teeth

Three included studies reported degree of relapse for orthodontically rotated teeth. All studies took alginate impressions, photographed original, rotational, and relapse casts, imported these images into a computer image analyzer, and measured the angles formed between the defined reference line and the incisal edge line of the experimental incisors. The percentage of relapse was the degree of relapse, divided by the total rotational movement of each tooth and multiplied by 100.

Human study

Jahanbin et al.⁸ recruited 12 rotated incisors in six patients and 11 rotated incisors in six patients for the LLLT group and control group, respectively. Continuous wavelength mode (810-nm wavelength) with an energy density of 35.7 J/cm² was applied during relapse for the LLLT group. Statistical analysis revealed that LLLT with high energy density was effective in alleviating relapse after 1 month compared to the control group.

Animal study

Twenty-eight mandibular lateral incisors in beagles were involved in the researches performed by Kim et al.⁹ and Salehi et al.²² Kim used pulsed wave with a 4.63–6.47-J/cm² energy density and 808-nm wavelength to irradiate incisors after removing the orthodontic appliance in the LLLT group and came to the conclusion that LLLT seemed to increase the relapse tendency of orthodontically rotated teeth over a short observation time of 4 weeks. Salehi et al. irradiated the experimental teeth with continuous wavelength of 810 nm and 31.8 J/cm² during the orthodontic movements in the LLLT group. The data analysis demonstrated that LLLT did reduce the relapse of rotational teeth, but the decreasing tendency was weakened over time since the difference between the LLLT group and control group was smaller after 3 months of observation compared to 1 month.

Adverse effect

Only one study⁹ included observed the adverse effect of LLLT on periodontal tissues, in which laser-aided CSF was also conducted on other experimental teeth. Compared to laser-aided CSF group, whose pocket depth increased by 0.67 mm averagely after 1 month of relapse in contrast with the initial level, the LLLT group showed no increase of pocket depth. Although there did exist gingival swelling during rotation of the teeth due to wearing the orthodontic appliance, gingivitis subsided and the gingival height returned to its original level at the end of experiment.

Histologic examination

The study conducted by Kim et al.⁹ used hematoxylin–eosin and Masson's trichrome staining to examine the tissue blocks, which were sectioned perpendicular to the long axis of the experimental teeth. Under light microscopy, the changes and thickness of the fiber bundles, as well as the phase of the blood vessels from LLLT group, were similar to those of control group.

Discussion

Rotation was quite different from the mesiodistal dental movement, and the mechanism for relapse of corrected tooth rotations to its pretreatment position has been surveyed since 1959 by Reitan,¹² who concluded that relapse of rotated tooth was caused primarily by a contraction of displaced supra-alveolar fibers. Further conclusions were drawn by Boese,¹⁰ who divided the phases of orthodontic rotational relapse into the following two parts. (A) In the first 8 weeks, following orthodontic rotation of a tooth, relapse was mainly caused by stretched principal fibers, which could be terminated by the remodeling of alveolar bone, providing new attachments for the principal fibers. (B) After the first 8 weeks, the relapse was caused by the supra-alveolar fibers. The proliferative response of oxytalan and collagen fibers in the supra-alveolar tissue caused by orthodontic tooth rotation and the stable attachments of the trans-septal fibers seemed responsible for this part of relapse. Edwards had similar findings.² This result was corroborated by an in vitro study,²³ in which transcription of collagen type I was increased and collagenase was decreased under centrifugal force. However, Redlich found disorganized, split, and ripped collagen fibers and revealed an increase in elastic fibers after orthodontic rotation and retention.²⁴ So they assumed that the relapse might not be due to “stretched” collagen fibers, but rather originated in the changing elastic properties of the whole gingival tissue. From the aforementioned discussion, we can deduce that the relapse of rotated teeth is related to the change of collagen and elastic fibers in periodontal and gingival tissues during rotation and retention. Moreover, the mechanism of CSF in reducing the relapse of rotational teeth can be ascribed to rearrangement of collagen and elastic fibers. However, the problem that plays a more important role in the relapse of rotational tooth, collagen or elastic fibers, needs to be explored further.

Collagen and elastic fibers in gingiva and periodontal ligament (PDL) are mainly secreted by fibroblasts. Several studies in vitro have indicated that LLLT can increase fibroblast cell proliferation in gingiva^25
–27 and PDL,²⁸ low energy density applied in these studies. The alteration of fibroblast proliferation on circumstance of laser irradiation may change the amount of fibers in periodontal tissues, and relapse of rotational teeth further. Since these changes were observed in vitro, the influence of LLLT on the amount of fibroblasts in vivo needs deeper studies.

As to the effect of LLLT at the molecular level, relevant research has discovered that LLLT can change the protein expression in cells, not only by upregulating but also by downregulating the content of different proteins.²⁵ A statistically significant increase in gene expression of collagen and vascular endothelial growth factor was also found in fibroblasts under laser irradiation.^29
–31 The induction of collagen synthesis by laser irradiation may be related to activation of TGF-β/Smad signaling pathway,³⁰ which plays an important role in the formation of extracellular matrix.

The photobiological effect of LLLT is on the basis of its influence on cells, especially the excitation of the respiratory chain in the mitochondria in cells. Evidence shows that mitochondria are sensitive to monochromatic to near-IR radiation.³² When irradiated in vitro at a wavelength of 660 nm and a fluence of 5 J/cm², enzyme in fibroblast mitochondria was influenced, in particular, cytochrome c oxidase,³³ which plays a role as possible photoacceptor. This leads to a cascade of reactions, including changes of mitochondrial morphology from a filamentous to a granular appearance, more extensive distribution,³⁴ increased mitochondria activity and ATP synthesis,³³ inducing reactive oxygen species (ROS) generation,³⁵ and the mitochondrial membrane potential is strengthened.³⁶ These changes may promote phosphorylation of Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) expressions³⁷ and activate the redox-sensitive NF-κB signaling pathways.³⁸ All these primary changes may cause a series of secondary effects, such as alteration of metabolic activity, upregulating or downregulating gene and protein expression,³⁹ which might contribute to the biostimulatory effects of action of LLLT.

Hu³⁷ irradiated melanoma cell line A2058 cells with He-Ne laser (632.8 nm), with dosages of 0.5, 1, 2 J/cm², and found that cytochrome c oxidase activity increased by about 70%, 140%, 170% after irradiation, respectively, compared with the control group. Further, LLLT in a greater scope of energy density was applied by Sharma et al.,⁴⁰ who irradiated primary mouse cortical neurons from mice with influence of 0.03, 0.3, 3, 10, or 30 J/cm² of 810-nm laser and found an increase in calcium, ATP, and mitochondrial membrane potential at lower fluences and a decrease at higher fluences. However, the production of ROS showed a different pattern—triphasic dose–response pattern,⁴¹ which displayed an increase at low fluences, followed by a decrease and a second larger increase at 30 J/cm². Wu et al.⁴² applied a much higher energy density 120 J/cm² in vitro to irradiate human lung adenocarcinoma cells and African green monkey SV40-transformed kidney fibroblast cells, which showed activation of caspase-3, accompanied by an immediate increase of ROS and decrease of mitochondrial membrane potential after irradiation. A mass of ROS generation may contribute to mitochondrial pore transition.⁴³ These changes indicated the activation of the mitochondrial/caspase-3 pathway, which can initiate and regulate cell apoptosis. Low energy density also can cause the increase of ROS in mitochondria after irradiation, but the amount of ROS does not reach the concentration that can trigger mitochondrial pore transition. On this occasion, an involvement of ROS might not cause cell apoptosis but enhances cell migration, proliferation, and adhension.^44,45 So, this might be the reason why low energy density can promote tissue metabolism, while high energy density suppresses the activity of irradiated tissues. This phenomenon suggests that the effect of LLLT has a biphasic dose response.⁴⁶ Many researches illustrated this biphasic dose response with the Arndt Schulz model,^41,45 but we preferred that the inverted U-shaped model⁴⁷ might be more accurate to describe this relationship between energy density applied and the biological effect, as shown in Fig. 2. Point A means proper energy density that can arouse the maximal stimulatory effect, while point B implies the critical point above which LLLT will cause inhibitory effect rather than stimulatory effect. We can get a better understanding of this biphasic dose–response effect of LLLT by making connection with the triphasic dose response of ROS produced by mitochondria after irradiation. Treated by LLLT with low energy density, an increase of ROS might contribute to the stimulatory effect of LLLT. With the energy density rising, production of ROS begins to descend, and so, the stimulatory effect caused by ROS decreases, which coincides with the segment from A to B in Fig. 2. As the energy density increases further, a large amount of ROS is generated, activating the mitochondrial/caspase-3 pathway and causing an inhibitory effect on irradiated cells and tissues. This corresponds to the segment after B in Fig. 2.

FIG. 2.

Biphasic dose response of LLLT described by the inverted U-shaped model. Point A means proper energy density that can arouse the maximal stimulatory effect, while point B implies critical point above which LLLT will cause inhibitory effect rather than stimulatory effect. LLLT, low-level laser therapy.

Studies have confirmed that the influence of laser irradiation is not only related to energy density^26,30,38,48 but also connected with wavelength,⁴⁹ cell type,³⁸ and treatment time.^26,28 So, under different kinds of situations (wavelength, cell type, etc.), the values of point A and point B in Fig. 2 vary a lot. Murayama⁵⁰ irradiated the glioblastoma cell with a diode laser at a wavelength of 808 nm and concluded that a relatively low energy density less than 5 J/cm² had a stimulatory effect on proliferation of normal cells, while energy density higher than 5 J/cm² had an inhibitory effect. This argument was not compatible with Zhang,⁵¹ who irradiated the Hela cells with a wavelength of 608 nm and summarized that laser irradiation lower than 25 J/cm² promoted cell viability while high dose impaired. As to point B regarding the effect of LLLT on relapse of rotational teeth in beagles, available data were insufficient to determine. Kim et al.⁹ applied a diode laser with 4.63–6.47 J/cm² energy density and under this condition, LLLT increased the relapse tendency and had a stimulatory effect. On the contrary, Salehi et al.²² irradiated the rotational teeth with laser of 31.8 J/cm²-energy density, which alleviates the relapse of rotational teeth and had an inhibitory effect. We can presume that point B might lie between these two values. More researches are in need to ascertain point A and point B in humans for different kinds of tissues so that we can apply suitable energy density for various purposes.

Salehi et al.²² observed that after 3 months of follow-up, the percentage of relapse was still lower than in the control group, but the degree of relapse failed to show the same results. This phenomenon suggested that the effect of LLLT on relapse of rotational tooth might change as time went by. Maybe this was also related to the fact that the maximum of relapse happened in the early time after rotation.⁴ So early application of LLLT after rotation is advised to decrease its relapse.

This systematic review included two animal experiments and one human study. Only one study described methods of randomization. One animal experiment used split-mouth design, namely both experimental and control sides were in the same participant and the assignment would not change. Although the allocation was not concealed, it would not result in bias. Thus, we gave“+” in allocation concealment. All studies recruited randomly selected dental models and calculated tooth rotation for the second time,^8,22 and the correlation coefficients were 0.997 and 0.97, which implied good reliability and reproducibility of these measurements. Double determination measurements were performed by two investigators independently,⁹ and so, we judged “Blinding of outcome assessment” to be “+.” Other bias in this article specialized in baseline imbalance between the LLLT and control group. Since there was no statistical significance of initial angle of rotation between the groups, we judged them to be “+” in “other bias.” In total, the quality of these three studies was high.

However, the foremost limitation in this review was that there were only three available studies, and only one was conducted on human beings. Although the arrangement of the supporting structures in man and the dog is fairly similar, the periodontal fiber bundles are coarser and the bone tissue is frequently denser in the dog than in human.¹² This confinement demonstrated disadvantage for this systematic review. In addition, there were some inconsistencies in the utilization of LLLT: Kim et al.⁹ and Jahanbin et al.⁸ irradiated teeth after rotation, while Salehi et al.²² applied irradiation during rotation. This dissimilarity may cause inconformity in the results. Further, in clinical practice, patients are ordered to wear retainers after active orthodontic treatment. In these studies, however, no retainers were used, which might cause potentially different effects since Kim et al.⁴⁸ found that the influence of LLLT on relapse was disparate with or without retainers. In the future, more well-designed RCTs involving human are required to further study the effect of LLLT on the relapse of rotational teeth.

Conclusions

According to the results of our systematic review, it seems that the effect of LLLT on relapse of corrected tooth rotations is related to energy density. Taking this one step further, low energy density seems to promote relapse, while high energy density might alleviate the relapse, which implies that LLLT has a biphasic dose–response effect. Also, early application of LLLT was suggested. Since available investigations are limited, the conclusion should be interpreted with caution, and more well-designed RCTs involving human are needed to get more clinically significant conclusions.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

References

Stewart

, Sherick

, Kramer

, Breining

. Use of relaxin in orthodontics. Ann N Y Acad Sci, 2005; 1041:379–387.

Edwards

. A surgical procedure to eliminate rotational relapse. Am J Orthod, 1970; 57:35–46.

Young

, Binderman

, Yaffe

, Beni

, Vardimon

. Fiberotomy enhances orthodontic tooth movement and diminishes relapse in a rat model. Orthod Craniofac Res, 2013; 16:161–168.

Brain

. The effect of surgical transsection of free gingival fibers on the regression of orthodontically rotated teeth in the dog. Am J Orthod, 1969; 55:50–70.

Boese

. Fiberotomy and reproximation without lower retention, nine years in retrospect: part I. Angle Orthod, 1980; 50:88–97.

Boese

. Fiberotomy and reproximation without lower retention, nine years in retrospect: part II. Angle Orthod, 1980; 50:169–178.

Taner

, Haydar

, Kavuklu

. Short-term effects of fiberotomy on relapse of anterior crowding. Am J Orthod Dentofacial Orthop, 2000; 118:617–623.

Jahanbin

, Ramazanzadeh

, Ahrari

, Forouzanfar

, Beidokhti

. Effectiveness of Er:YAG laser-aided fiberotomy and low-level laser therapy in alleviating relapse of rotated incisors. Am J Orthod Dentofacial Orthop, 2014; 146:565–572.

Kim

, Paek

, Park

, Kang

, Park

. Laser-aided circumferential supracrestal fiberotomy and low-level laser therapy effects on relapse of rotated teeth in beagles. Angle Orthod, 2010; 80:385–390.

10.

Boese

. Increased stability of orthodontically rotated teeth following gingivectomy in Macaca nemestrina . Am J Orthod, 1969; 56:273–290.

11.

Beertsen

. Remodelling of collagen fibers in the periodontal ligament and the supra-alveolar region. Angle Orthod, 1979; 49:218–224.

12.

Reitan

. Tissue rearrangement during retention of orthodontically rotated teeth. Angle Orthod, 1959; 29:105–113.

13.

Mester

, Szende

, Gärtner

. The effect of laser beams on the growth of hair in mice. Radiobiol Radiother (Berl), 1968; 9:621–626.

14.

Omasa

, Motoyoshi

, Arai

, Ejima

, Shimizu

. Low-level laser therapy enhances the stability of orthodontic mini-implants via bone formation related to BMP-2 expression in a rat model. Photomed Laser Surg, 2012; 30:255–261.

15.

Lim

, Lew

, Tay

. A clinical investigation of the efficacy laser therapy in reducing orthodontic postadjustment pain. Am J Orthod Dentofacial Orthop, 1995; 108:614–622.

16.

Artes-Ribas

, Arnabat-Dominguez

, Puigdollers

. Analgesic effect of a low-level laser therapy (830 nm) in early orthodontic treatment. Lasers Med Sci, 2013; 28:335–341.

17.

Albrektson

, Hedstrom

, Bergh

. Recurrent aphthous stomatitis and pain management with low-level laser therapy: a randomized controlled trial. Oral Surg Oral Med Oral Pathol Oral Radiol, 2014; 117:590–594.

18.

Fornaini

, Brulat

, Milia

, Rockl

, Rocca

. The use of sub-ablative Er:YAG laser irradiation in prevention of dental caries during orthodontic treatment. Laser Ther, 2014; 23:173–181.

19.

Miresmaeili

, Farhadian

, Rezaei-soufi

, Saharkhizan

, Veisi

. Effect of carbon dioxide laser irradiation on enamel surface microhardness around orthodontic brackets. Am J Orthod Dentofacial Orthop, 2014; 146:161–165.

20.

Yilmaz

, Cengiz

, Kurtulmus-Yilmaz

, Leblebicioglu

. Effectiveness of Er,Cr:YSGG laser on dentine hypersensitivity: a controlled clinical trial. J Clin Periodontol, 2011; 38:341–346.

21.

, He

, Chen

, et al. Efficacy of low-level laser therapy for accelerating tooth movement during orthodontic treatment: a systematic review and meta-analysis. Lasers Med Sci, 2015; 30:1609–1618.

22.

Salehi

, Heidari

, Tanideh

, Torkan

. Effect of low-level laser irradiation on the rate and short-term stability of rotational tooth movement in dogs. Am J Orthod Dentofacial Orthop, 2015; 147:578–586.

23.

Redlich

, Palmon

, Zaks

, Geremi

, Rayzman

, Shoshan

. The effect of centrifugal force on the transcription levels of collagen type I and collagenase in cultured canine gingival fibroblasts. Arch Oral Biol, 1998; 43:313–316.

24.

Redlich

, Rahamim

, Gaft

, Shoshan

. The response of supraalveolar gingival collagen to orthodontic rotation movement in dogs. Am J Orthod Dentofac Orthop, 1996; 110:247–255.

25.

Ogita

, Tsuchida

, Aoki

, et al. Increased cell proliferation and differential protein expression induced by low-level Er:YAG laser irradiation in human gingival fibroblasts: proteomic analysis. Lasers Med Sci, 2015; 30:1855–1866.

26.

Almeida-Lopes

, Rigau

, Zângaro

, Guidugli-Neto

, Jaeger

. Comparison of the low level laser therapy effects on cultured human gingival fibroblasts proliferation using different irradiance and same fluence. Lasers Surg Med, 2001; 29:179–184.

27.

Azevedo

, de Paula Eduardo

, Moreira

, de Paula Eduardo

, Marques

. Influence of different power densities of LILT on cultured human fibroblast growth: a pilot study. Lasers Med Sci, 2006; 21:86–89.

28.

Kreisler

, Christoffers

, Willershausen

, d'Hoedt

. Effect of low-level GaAlAs laser irradiation on the proliferation rate of human periodontal ligament fibroblasts: an in vitro study. J Clin Periodontol, 2003; 30:353–358.

29.

Martignago

, Oliveira

, Pires-Oliveira

, et al. Effect of low-level laser therapy on the gene expression of collagen and vascular endothelial growth factor in a culture of fibroblast cells in mice. Lasers Med Sci, 2015; 30:203–208.

30.

Dang

, Liu

, et al. The 800-nm diode laser irradiation induces skin collagen synthesis by stimulating TGF-β/Smad signaling pathway. Lasers Med Sci, 2011; 26:837–843.

31.

Gal

, Mokry

, Vidinsky

, et al. Effect of equal daily doses achieved by different power densities of low-level laser therapy at 635 nm on open skin wound healing in normal and corticosteroid-treated rats. Lasers Med Sci, 2009; 24:539–547.

32.

Karu

. Primary and secondary mechanisms of action of visible to near-IR radiation on cells. J Photochem Photobiol B, 1999; 49:1–17.

33.

Houreld

, Masha

, Abrahamse

. Low-intensity laser irradiation at 660 nm stimulates cytochrome c oxidase in stressed fibroblast cells. Lasers Surg Med, 2012; 44:429–434.

34.

Pires Oliveira

, de Oliveira

, Zangaro

, Soares

. Evaluation of low-level laser therapy of osteoblastic cells. Photomed Laser Surg, 2008; 26:401–404.

35.

Lavi

, Shainberg

, Friedmann

, et al. Low energy visible light induces reactive oxygen species generation and stimulates an increase of intracellular calcium concentration in cardiac cells. J Biol Chem, 2003; 278:40917–40922.

36.

Lane

. Cell biology: power games. Nature, 2006; 443:901–903.

37.

, Wang

, Yu

, Lan

, Chen

, Yu

. Helium-neon laser irradiation stimulates cell proliferation through photostimulatory effects in mitochondria. J Invest Dermatol, 2007; 127:2048–2057.

38.

Moore

, Ridgway

, Higbee

, Howard

, Lucroy

. Effect of wavelength on low-intensity laser irradiation-stimulated cell proliferation in vitro. Lasers Surg Med, 2005; 36:8–12.

39.

Rojas

, Gonzalez-Lima

. Neurological and psychological applications of transcranial lasers and LEDs. Biochem Pharmacol, 2013; 86:447–457.

40.

Sharma

, Kharkwal

, Sajo

, et al. Dose response effects of 810 nm laser light on mouse primary cortical neurons. Lasers Surg Med, 2011; 43:851–859.

41.

Huang

, Sharma

, Carroll

, Hamblin

. Biphasic dose response in low level light therapy—an update. Dose Response, 2011; 9:602–618.

42.

, Xing

, Wang

, Chen

. Mechanistic study of apoptosis induced by high-fluence low-power laser irradiation using fluorescence imaging techniques. J Biomed Opt, 2007; 12:064015.

43.

Belletti

, Uggeri

, Mergoni

, et al. Effects of 915 nm GaAs diode laser on mitochondria of human dermal fibroblasts: analysis with confocal microscopy. Lasers Med Sci, 2014; 30:375–381.

44.

Grossman

, Schneid

, Reuveni

, Halevy

, Lubart

. 780 nm low power diode laser irradiation stimulates proliferation of keratinocyte cultures: involvement of reactive oxygen species. Lasers Surg Med, 1998; 22:212–218.

45.

Huang

, Chen

, Carroll

, Hamblin

. Biphasic dose response in low level light therapy. Dose Response, 2009; 7:358–383.

46.

Albuquerque-Pontes

, Vieira Rde

, Tomazoni

, et al. Effect of pre-irradiation with different doses, wavelengths, and application intervals of low-level laser therapy on cytochrome c oxidase activity in intact skeletal muscle of rats. Lasers Med Sci, 2015; 30:59–66.

47.

Davis

, Svendsgaad

. U-shaped dose-response curves: their occurence and implications for risk assessment. J Toxicol Environ Health, 1990; 30:71–83.

48.

Kim

, Kang

, Park

, Kim

, Park

. Effects of low-intensity laser therapy on periodontal tissue remodeling during relapse and retention of orthodontically moved teeth. Lasers Med Sci, 2013; 28:325–333.

49.

Demidova-Rice

, Salomatina

, Yaroslavsky

, Herman

, Hamblin

. Low-level light stimulates excisional wound healing in mice. Lasers Surg Med, 2007; 39:706–715.

50.

Murayama

, Sadakane

, Yamanoha

, Kogure

. Low-power 808-nm laser irradiation inhibits cell proliferation of a human-derived glioblastoma cell line in vitro. Lasers Med Sci, 2011; 27:87–93.

51.

Zhang

, Xing

, Gao

. Low-power laser irradiation activates Src tyrosine kinase through reactive oxygen species-mediated signaling pathway. J Cell Physiol, 2008; 217:518–528.