Acceleration of Orthodontic Tooth Movement Overview

Abstract

The achievable rate of orthodontic tooth movement (OTM) is a crucial predictor of treatment time, with most studies estimating 1 mm of movement every month. Accelerating OTM is important due to the annual increase in adult patients seeking orthodontic treatment, as they are not growing and have slower rates of tissue metabolism and regeneration. Various surgical and nonsurgical techniques have been used to accelerate tooth movement by interfering with biological pathways affecting bone cell activity. Approaches to OTM acceleration can be invasive, minimal, and micro- or non-invasive, and can be achieved through pharmacological agents, physical devices, vibration, low-intensity pulsed ultrasound, direct electric current, and photobiomodulation.

1. Introduction

The achievable rate of orthodontic tooth movement (OTM) is a fundamental predictor of orthodontic treatment time. Much study has been undertaken to identify the rate of tooth movement, with most studies estimating 1 mm of tooth movement every month [1, 2, 3].

1.1 Attempts to accelerate OTM

The OTM process is ultimately limited by the local and systemic biological responses of the tooth and its supporting structure in relation to the general heath. Therefore, customization of brackets and wires have greatly improved treatment efficiency but cannot rely only on this approach to shorten the treatment duration [4].

1.2 Importance of acceleration of OTM

According to the published survey, the annual increase in the number of adult patients seeking orthodontic treatment was significant [5]. Adult patients can benefit the most from accelerated orthodontic treatment because they are not growing and have much slower rates of local tissue metabolism and regeneration than adolescents [6]. Furthermore, adult patients are more susceptible to periodontal complications and other time-dependent side effects (e.g., oral hygiene issues, root resorption). As a result, there is an additional practical advantage to accelerating treatment in adults [7].

1.3 Rational of OTM acceleration

Because alveolar bone modeling/remodeling is a critical component of orthodontic tooth movement, several surgical and nonsurgical techniques have been used to accelerate tooth movement by interfering with biological pathways affecting the activity of bone cells (osteoclasts, osteoblasts, and osteocytes) [7, 8].

2. Approaches to OTM acceleration

It can be broadly classified into 2 main approaches, Surgical and Non Surgical [9].

2.1 Surgical approaches

2.1.1 Invasive surgical approach

Corticotomy

2.1.2 Minimal invasive surgical approaches

1. Corticision

2. Peizosicion,

3. Interseptal alveolar surgery

4. Full-thickness mucoperiosteal flap elevation alone. (New minimal invasive surgical technique)

2.1.3 Micro invasive surgical approaches

Aleveocentesis

2.2 Non-surgical approach (not invasive)

1. Pharmacological agents [9]

   1. Vitamin D

   2. Prostaglandin E1 and 2

   3. Parathyroid hormone

   4. Thyroxin hormone

   5. Relaxin

   6. Cytokines

2. Physical devices

   1. Vibration (Acceledent)

   2. Low-intensity pulsed ultrasound (Aevo system)

   3. Direct electric current

   4. Photobiomodulation:

      • Biolux

      • Orthopulse

      • Low-level laser therapy

2.3 Surgical approaches

Surgical techniques to accelerate orthodontic treatment have been tested for over 100 years in clinical practice.

Regional acceleratory phenomenon (RAP)

This is a method for increasing bone modeling/remodeling rates while decreasing bone density. The RAP is a series of tissue reactions that occur during the repair of injured bone. It was described as a “complex reaction of mammalian tissues to various noxious stimuli.” Noxious stimuli included crushing traumas, fractures, and bone surgeries. It occurs regionally and involves both hard and soft tissues, and is characterized by an acceleration and dominance of most ongoing normal vital tissue processes [9, 10].

The RAP mechanisms include accelerated bone turnover and modeling, cellular metabolism, and hard and soft tissue growth. The RAP also produces a brief decrease in regional bone density in bone. This decrease in regional bone density may result in quicker tooth movement during orthodontic therapy [10].

2.3.1 Invasive surgical approaches

2.3.1.1 Corticotomy

2.3.1.1.1 Definition

It is a surgical approach in which the medullar bone is left unaltered and only applies cuts in the cortical bone. In contrast, an osteotomy involves making a surgical incision that penetrates the cortical and medullar bone. Kole attempted it for the first time in orthodontics in 1959 [11].

2.3.1.1.2 Rational

It is believed that the continuity and thickness of the denser layer of cortical bone offers the most resistance to rapid tooth movement. Early, it was attributed the accelerated OTM by selective corticotomy to moving “blocks of bone” and this interpretation of the rapid tooth movement prevailed until 2001; it was discovered that the rapid tooth movement was due to transient localized demineralization-remineralization process (RAP) and was not the result of bony block movement as was suggested earlier [12].

The Accelerated Osteogenic Orthodontics (AOO) approach, and more recently the Periodontally AOO (PAOO) surgical treatment, combines the improved corticotomy-aided orthodontic technique with alveolar augmentation employing particulate bone transplant surgery. In the majority of cases, this has resulted in orthodontic treatment times that are 1/3 the length of those of traditional orthodontics [13].

2.3.1.1.3 Technique

The conventional corticotomy procedure involves elevation of full-thickness mucoperiosteal flaps, buccally and/or lingually, followed by placing the corticotomy cuts using either a micromotor under irrigation or piezosurgical instruments [14]. This can be followed by placement of a graft material, wherever required, to augment thickness of bone [15, 16].

2.3.1.1.4 Advantages

• It has been proven successfully by many authors to accelerate tooth movement by 60–75% of total treatment time [17, 18].

• Bone augmentation can be done, thereby preventing periodontal defects, which might arise as a result of thin alveolar bone [15, 16].

• Corticotomy procedure causes minimal changes in the periodontal attachment apparatus [19].

2.3.1.1.5 Disadvantages

1. High chances of damage to adjacent vital structures as well periodontium or root injury [17].

2. Post-operative pain, swelling, chances of infection, and vascular necrosis.

3. A lack of patient acceptance.

2.3.1.2 Corticision

2.3.1.2.1 Definition

It is one of the minimally invasive options for creating a surgical injury to the bone that does not require flap reflection [20].

2.3.1.2.2 Rational

This surgical injury is thought to be sufficient to cause the RAP effect and cause the teeth to move quickly following orthodontic therapy [20].

2.3.1.2.3 Technique

To get through the gingiva and cortical bone without raising flaps into the alveolar bone, a strengthened scalpel and a mallet are utilized.

2.3.1.2.4 Advantages

1. Corticision has been shown to be clinically useful in OTM acceleration [20].

2. Avoiding the obvious drawbacks of traditional corticotomy procedures, such as injury to surrounding critical structures [20].

2.3.1.2.5 Disadvantages

The inability to graft soft or hard tissues to address bone deficiencies throughout the surgery.

2.3.1.3 Piezocision

2.3.1.3.1 Definition

It is one of the minimally invasive options for creating a surgical damage to the bone that does not require flap reflection [20]. Piezosurgery, rather than burs, was utilized in 2007 in conjunction with standard flap elevations to generate an environment favorable to fast tooth movement [21].

2.3.1.3.2 Rational

This surgical damage is thought to be sufficient to cause the RAP effect and cause the teeth to move quickly. Piezocision is a potential technology for tooth acceleration. The micro-incisions are localized to the buccal cortex and initiate the RAP without engaging the palatal or lingual cortex, making it a minimally invasive method. Micrometric and selective incisions are produced by a piezoelectric device [21].

2.3.1.3.3 Technique

It begins with a primary incision on the buccal gingiva, followed by incisions on the buccal cortex with a piezosurgical knife [22].

2.3.1.3.4 Advantages

1. Safe and precise osteotomies with no osteonecrosis damage [9, 23].

2. There is no periodontal damage.

3. It can be used in conjunction with Invisalign, resulting in a more cosmetic appearance and shorter treatment time.

4. Enables hard or soft tissue transplantation through selective tunneling to treat gingival recessions or bone shortages in patients.

5. Increased patient acceptability.

2.3.1.3.5 Disadvantages

1. The risk of root injury if done incorrectly [9, 23].

2. Requires a specialized instrument (Piezocision kit).

3. Specifically during orthodontic treatment [20].

2.3.1.4 Interseptal alveolar surgery

2.3.1.4.1 Definition

Interseptal alveolar surgery, also known as distraction osteogenesis, is classified into two types: PDL distraction and dentoalveolar bone distraction; rapid canine distraction is an example of both [24].

2.3.1.4.2 Rational

Distraction osteogenesis arose from early studies on limb lengthening. It was initially employed to treat craniofacial skeletal dysplasia, but the procedure was later expanded to include rapid OTM. In this application, compact bone is replaced by woven bone, which makes OTM easier and faster due to the lower resistance of the bone [25].

2.3.1.4.3 Technique

The interseptal bone distal to the canine is surgically undermined at the same time as the first premolars are extracted in rapid canine distraction. This reduced resistance at the pressure point [25].

2.3.1.4.4 Advantage

It is more convenient for the patient if it is done during the extraction procedure [15].

2.3.1.4.5 Disadvantages

The RAP can be located solely in the cortex [25].

2.3.1.5 Full-thickness mucoperiosteal flaps

2.3.1.5.1 Definition

It is a novel method in which a full-thickness mucoperiosteal flap (FTMPF) is elevated from the coronal side, primarily in the premolar region, in situations where the first premolar is suggested to be extracted, followed by canine retraction.

2.3.1.5.2 Rational

In 1994, a study [26] reported that RAP is caused by an increase in FTMPF in the mandible of rats. Rats with raised flaps lost alveolar bone as early as 10 days, and this loss was more widespread in animals with both the buccal and lingual flaps raised. Maximum resorption occurred 3 weeks after surgery, and bone volume appeared to rebound to nearly normal levels 120 days later. A later study [27] published in 2001 found that local modeling/remodeling of bone is greater when the flap is approached from the coronal rather than the apical side [26].

Another animal study published in 2017 found that FTMPF elevation increased the rate of tooth displacement by 24–31%. The enhanced tooth motions caused by flap-only surgery were significantly less than those seen with corticotomy treatments [28]. However, due to differences in bone composition, density, quality, and turnover rates, rats are not appropriate models for humans. Furthermore, conducting flap surgery on rats produces a painful response that is likely to be larger than that produced by people [26].

In 2020, a human split mouth design clinical trial was conducted to assess the accelerated effect of FTMPF increase alone on canine retraction. Just before maxillary first premolar extraction, the flap was lifted with palatal tunnel flap from the mesial interdental papilla of the maxillary canine to the mesial interdental papilla of the second maxillary premolar. According to study, the FTMPF might reduce the time necessary for complete canine retraction by 25% [29].

Elevation of an FTMPF raises the rate of OTM by reducing the volume and apparent density of medullary bone by around 9% [28]. The reductions in bone volume fraction and density were minor, comparable to those previously linked to RAP [30, 31]. The RAP involves the injured region, and the shift between involved and uninvolved bone sections is gradual. Regional bone vascularization is derived from two sources: medullary bone and periosteum. Corticotomy studies, on the other hand, have neglected to account for putative RAP effects caused by the raised periosteal flap during the corticotomy process [32].

2.3.1.5.3 Advantages

Elevation of an FTMPF from a coronal approach increases OTM rates clinically. Because flap elevation can result in alveolar bone loss [29, 33, 34, 35], doing a standalone flap surgery for a 25–31% rise in the incidence of OTM requires cautious evaluation. If surgery is being undertaken for another reason, the higher rate of OTM owing to flap elevation should be considered. For example, if orthodontic treatment is to begin soon after premolar extraction, the clinician may choose to elevate a flap at the moment of extraction. This is predicated on the lack of a substantial difference in long-term bone healing after extractions with or without a flap [35, 36].

2.3.1.5.4 Disadvantage

There are still insufficient reports on the long-term effects of this procedure on the level of attached gingival tissue and crestal bone.

2.3.2 Micro-osteoperforations (alveocentesis)

2.3.2.1 Definition

In 2011, a new microinvasive technology was unveiled. It was created and patented to be used as a simple in-office technique to induce alveolar bone modeling/remodeling. This procedure was known as alveocentesis, which literally means “punching bone.” The PROPEL system [24, 25, 37] was developed to commercialize this innovative method.

2.3.2.2 Rational

It increases cytokine activity, which speeds up alveolar bone modeling/remodeling to achieve RAP. It was stated that the PROPEL system’s micro-osteoperforations cause RAP via cytokine action, allowing for faster OTM [28]. Performing micro-osteoperforations (MOPs) on alveolar bone during OTM may encourage the development of inflammatory markers, which in turn may boost osteoclast activity and the pace of OTM, according to animal studies. It causes a 2.3-fold acceleration in canine retraction [9]. Its acceleration impact, however, is still being studied [37].

2.3.2.3 Technique

Micro-osteoperforations decrease the invasiveness of surgical bone irritation. Propel Orthodontics’ gadget is used to generate micro-osteoperforations (MOPs) on alveolar bone [24].

2.3.2.4 Advantages

1. MOPs are an efficient, comfortable, and risk-free method of accelerating OTM.

2. Patients reported just minor discomfort at the location of the MOPs. On days 14 and 28, there was little to no pain [9].

3. Propel is unusual in that it may be targeted to specific teeth or quadrants rather than being applied to the entire dentition at once, which may result in anchorage concerns [37].

4. It also provides a less expensive option to implants for adults with disfigured dentitions, which frequently require orthodontic closure of the edentulous region [24].

2.3.2.5 Disadvantages

Although the rate of tooth movement increased following MOP, at least one study found more apical root resorption. As a result, the use of MOP might be advised after evaluating the benefits and drawbacks of this intervention for each patient [37].

2.4 Non surgical approaches

2.4.1 Pharmacological agents

2.4.1.1 Vitamin D

As more osteoblasts are seen on the side where vitamin D3 was injected [9], research has shown that vitamin D3 may be more helpful in bone turnover (remodeling) than in speeding up tooth movement. Increases in the levels of the enzyme lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) are the negative effects of vitamin D injection in the PDL [38, 39]. On the other hand, a recent prospective split mouth clinical trial discovered that experimental teeth that received local vitamin D3 injections moved noticeably more slowly than corresponding control teeth [9].

2.4.1.2 Prostaglandins

Human experiments using chemically created PGE2 revealed that the rate of canine retraction was 1.6 times quicker than the control side. A generalized increase in the inflammatory state and root resorption are the adverse effects of prostaglandin [40, 41].

2.4.1.3 Parathyroid hormone

Parathyroid hormone (PTH) has been demonstrated to speed up OTM in rats, where implantation in the dorsocervical area and daily infusions of 1 to 10 μg/100 g of body weight/day caused molars to migrate 2 to 3 times more quickly mesially. According to several research, local PTH injections cause local bone resorption; for this reason, local PTH injections are preferable to systemic PTH injections [42, 43].

2.4.1.4 Thyroid hormone

Thyroxine hormone plays a crucial role in normal growth and development of vertebrate bones [44]. Previous studies showed that thyroxine hormone administration in rats had increased the speed of OTM by stimulating the osteoclastic activity due to prostaglandin increase. Moreover, the risk of root resorption was decreased too [44, 45, 46, 47, 48, 49].

2.4.1.5 Relaxin

PDL reorganization and mechanical strength are decreased by relaxin. As a result, it could help lower the rate of relapse. Experiments on rats suggest significant effect of relaxin on OTM acceleration; however, similar studies on humans suggest exactly the opposite [14, 42].

2.4.1.6 Cytokines

Cytokines such as interleukins IL-1, IL-2, IL-3, IL-6, IL-8, and tumor necrosis factor alpha (TNF) were found to play a major role in bone modeling/remodeling by stimulation of osteoclast function through its receptor on osteoclasts [50].

RANKL is another cytokines involved in the acceleration of OTM, which is an osteoblast a membrane-bound protein that binds to the RANK receptor on osteoclasts, resulting in osteoclast activation [51, 52, 53].

On the other hand, RANKL can also bind to OPG, which is also secreted by osteoblast. This results in decreased osteoclast activation since if the RANKL binds to OPG, there is less RANKL to bind to RANK. The process of bone modeling/remodeling is a function of the RANKL/RANK/OPG system [54, 55].

The RANKL/ OPG ratio in the gingival clavicular fluid (GCF) is decreased by age, which explains the difference in OTM rate between adult and young patients [54].

The hypothesis about the influence of the OPG/RANK/RANKL pathway on the external root resorption process is also consistent with findings in which a dramatic increase in apical external root resorption concurrent with orthodontic forces was observed when there was an imbalance in OPG/RANKL. This could be explained due to levels of receptor activator of RANKL and macrophage colony-stimulating factor (M-CSF), the odontoblasts or progenitors derived from apical dental papilla transform into resorbing odontoclasts that cause external apical root resorption [55].

2.4.2 Physical devices

2.4.2.1 Vibration

Recently, a product by the name AcceleDent has been introduced, which makes use of the vibrations/micro-impulses to accelerate OTM.

AcceleDent [15].

• Easy usage.

• Hands-free gadget with a mouthpiece that is put over the braces already in place.

• It is a portable/chargeable device.

2.4.2.2 Low-intensity pulsed ultrasound (Aevo system)

Existing low-intensity pulsed ultrasound (LIPUS) therapies have been proven to accelerate the repair of long bone fractures. This proven history inspired the development of the Aevo system [15, 56].

2.4.2.3 Direct electric current

This method was only tested on animals, where local responses on bone activity were produced by supplying direct current to the anode at pressure sites and the cathode at tension sites (by 7 V). Clinical testing was challenging due to the devices’ size and the source of energy. There have been several attempts to create bio-catalytic fuel cells that use glucose and enzymes as fuel to produce energy intraorally [4, 38].

2.4.2.4 Photobiomodulation

Photobiomodulation (PBM), attempts to use low-energy lasers or light-emitting diodes (LED) to modify cellular biology by increased mitochondrial metabolism due to exposure to light in the red to near-infrared (NIR) range (600–1000 nm). It could be useful in wound healing and the promotion of angiogenesis in skin, bone, muscle, and nervous tissues [39, 57, 58].

2.4.2.4.1 The biolux LED device

The LED device is a hard plastic case with sponge insulation, which is provided to lessen impact damage. Each device is composed of a facemask with LED arrays, a power supply, and a handheld controller unit. Each face mask unit is positioned to ensure a firm and reproducible position on the face with the LED arrays parallel to the occlusal plane of the patient. The LED array was positioned to target the root of the tooth undergoing OTM [9].

2.4.2.4.2 OrthoPulse system

An intraoral device and a portable controller make up OrthoPulseTM. The CPU, screen, and controls for the menu-driven software are all housed in the controller. A flexible circuit with LED arrays integrated in medical-grade silicone makes up the mouthpiece. The alveolus receives light through the buccal alveolar soft tissue. It emits near-infrared light with a constant peak wavelength of 850 nm. In order to produce a mean energy density of around 9.3 J/cm² at the surface of the LED array, patients underwent an average of 3.8 minutes of buccal-only therapy per arch every day. This was done using an average power density of 42 mW/cm². The amount of heat produced as a consequence of producing light was measured and kept within the limits established by the safety requirements for electro-medical devices [59].

2.4.2.4.3 Low-level laser therapy

Photobiomodulation by low-level laser therapy is one of the most promising approaches today. “Light Amplification by Stimulated Emission of Radiation” is what the term “laser” stands for, and it was first used about 60 years ago. American scientist Maiman created the first functional laser in 1960 using a synthetic ruby crystal comprised of aluminum oxide and chromium oxide [56, 60, 61].

2.4.2.4.3.1 Dental laser

2.4.2.4.3.1.1 Laser main components

• Energy source [61]

• Active medium

• Set of two or more mirrors that form a resonator.

2.4.2.4.3.1.2 Laser characteristics

• Monochromatic: single wavelength [37]

• Coherence: Singled phase leads to increase light intensity

• Collimation: The rays are parallel to each other.

2.4.2.4.3.1.3 Laser production

Laser light is produced by the stimulation of the active medium with an external agent such as a flash lamp strobe device, an electrical current, or coil [61]. The wavelength is determined primarily by the active medium, which can be a gas, crystal, or solid-state conductor [37]. Lasers used in dental practice vary between wavelengths of 488 nm and 10,600 nm [62].

2.4.2.4.3.1.4 Dental laser classification

Dental lasers is classified according to [63]:

• Emission type: Spontaneous/stimulated

• Output power: High-powered, mid-powered, or low-powered

• Active medium: Liquid state (e.g., He-Ne laser), gas state (e.g., Argon, CO₂ laser), solid state (e.g., Nd: YAG, Er: YAG), or semiconductor (e.g., Ga-Al-As diode laser)

• Target tissue: Hard or soft tissue

2.4.2.4.3.1.5 Factors controlling the tissue effect of dental laser

In dental office, there are high-powered lasers and low-powered lasers [64].

• High-powered: The light energy of the laser is converted into heat energy (photothermal reaction), resulting in photoablation and consequent breakdown of the tissue. This photomechanical interaction which then gives rise to rupture of the tissue;

• Low-level laser is used for photochemical effects on the tissues. Low-level laser therapy (LLLT) employs red and infrared light to promote the biological cellular activity and reduces inflammatory response and associated pain.

Laser effects of the on-target tissues depend on:

• The wavelength [65].

• Output power.

• Exposure duration and repetition rate.

• Continuous or pulsed irradiation.

• The amount of energy delivered to the tissue (laser beam size).

• Physical properties of irradiated tissue.

2.4.2.4.3.1.6 Types of dental lasers

Currently available lasers include the following [66].

• Argon laser

• He-ne, Nd: Yag

• Surface absorption-type CO₂

• Er: Yag laser

• Diode lasers

2.4.2.4.3.1.6.1 Argon laser

The argon laser, the active medium of which is argon gas, produces light at two wavelengths. The 488 nm blue light is commonly used to initiate the polymerization of restorative composite materials. It is often used for hemorrhage control in gingival surgery, dental detection cracks, and decay by transillumination technique [62, 67].

2.4.2.4.3.1.6.2 CO₂ laser

CO₂ gas serves as the laser’s active medium. It emits light with a wavelength of 10,600 nm, which the human eye cannot see. In comparison with other dental laser systems, this wavelength has the maximum absorbance in hydroxyapatite and a very high absorption in water. The CO₂ laser is frequently used for soft tissue surgery due to its benefits, which include quick soft tissue removal, excellent hemostasis, and minimal depth of penetration. The tooth structure surrounding the soft-tissue surgical site needs to be carefully preserved while employing a CO₂ laser. Hard tissue applications are not appropriate for these lasers [65].

2.4.2.4.3.1.6.3 Erbium lasers

Erbium lasers are now the most popular choice for dental purposes. Dentists employ erbium lasers of the Er: YAG and Er, Cr: YSGG types. The active material in the Er: YAG laser (2940 nm) is YAG, whereas the Er, Cr: YSGG laser (2790 nm) uses solid yttrium, scandium, and garnet. Both wavelengths have the largest water and hydroxyapatite absorption of any dental laser. Erbium lasers work well to remove hard tissues because water and hydroxyapatite are abundant in both bone and teeth [67, 68, 69, 70, 71].

2.4.2.4.3.1.6.4 Diode laser

At high power, diode lasers can be used to perform incision and hemostasis of soft tissue. Laser therapy can aid in repairing the mucosa, controlling pain, and accelerating wound healing through bactericidal and detoxifying effects [71]. Whereas, at low power, they can be used for periodontal therapy and treatment of dentinal hypersensitivity [53, 72].

Diode laser has a wide range of clinical applications due to [72, 73].

• High penetrant.

• Minimum water absorption.

• Inexpensive devices.

• Easy maintenance.

• Laser treatment beam available in seconds after system activation, compared to minutes for other systems.

• Diode lasers consume minimal power compared to other systems.

• Small laser system takes up minimal office space and offers portability due to its lightweight design.

2.4.2.4.3.1.7 Laser safety and harmful effects

According to the standards of American National Standards Institute and Occupational Safety, lasers are classified into classes based on potential danger [74, 75]:

Class I: Low-powered lasers; safe to view.

Class IIa: Low-powered visible lasers. Damage only if one looks directly along the beam for longer than 1.00 s.

Class II: Low-powered visible lasers. Damage only if one looks directly along the beam for longer than 0.25 s.

Class IIIa: Medium-powered lasers that are not dangerous when viewed for less than 0.25 s.

Class IIIb: Medium-powered lasers are hazardous when seen straight along the beam for even a brief period of time.

Class IV: These powerful, hazardous lasers have the potential to harm the skin and eyes. Even the transmitted or reflected rays might be harmful. It is essential to implement the necessary safety precautions. The majority of lasers used in medicine and dentistry are within this group.

2.4.2.4.3.1.8 Risks of LLLT

LLLT is a class IIIb hazardous substance that can harm the retina. These lasers can be harmful to unprotected eyes for any amount of time if viewed directly or via reflecting light. Therefore, eye protection should be worn by the patient, the practitioner, and anybody else in the restricted area. The wavelength for which protection is provided should be written on all protective eyewear, including glasses and goggles [74].

There have been no reports that LLLT could cause [75]:

• Root resorption.

• Alveolar bone resorption.

• Any adverse effects on oral mucosa, gingiva, and periodontal ligament.

• Loss of dental pulp vitality.

2.4.2.4.3.2 Advantages of using LLLT in OTM acceleration

1. Non-invasive technique.

2. Helps in decreasing wire size-upgrading pain.

3. Provide fair safety to irradiated tooth and periodontium.

4. Easy to perform.

5. It also has a dose-dependent effect on alveolar bone modeling/remodeling and proliferation in vivo.

Many studies have been shown, a significant bio-stimulatory effect observed as accelerated OTM [29, 76, 77, 78, 79, 80, 81]. A systematic review suggests LLLT effectiveness, but caution should be exercised due to small sample sizes, heterogeneity, and potential bias risks [75].

2.4.2.4.3.3 Indication for LLLT usage in OTM acceleration

LLLT is recommended for patients willing to attend multiple times with short laser intervals [7, 79].

2.4.2.4.3.4 Contraindications for LLLT usage in OTM acceleration

• Cancerous and pre-cancerous lesion in the oral cavity [7].

• Patient with coagulation disorders due to its effect on blood flow.

• Patients with epilepsy because they may have a seizure during irradiation.

• Patients with hyper- or hypothyroid conditions, irradiation over the thyroid gland should be avoided to prevent undesirable effects [7].

2.4.2.4.3.4.1 Mode of action of LLLT on OTM

To our knowledge, the effects of LLLT on OTM with the evaluation of inflammatory cytokines involved during bone modeling/remodeling have not been well investigated until now. Assessment of biomarkers of bone modeling/remodeling during laser irradiation could provide an understanding of the mechanism of accelerated tooth movement with this novel approach [81].

2.4.2.4.3.4.1.1 Tissue response to LLLT

The effect of LLLT is photochemical not thermal which is divided into Primary and Secondary responses:

2.4.2.4.3.4.1.1.1 Primary response

1. Absorption of photons of LLL by a photoacceptor molecule, also called a chromophore [64, 82, 83, 84].

2. A key photoacceptor of light is Cytochrome C Oxidase [85, 86].

   • It is an integral membrane protein of mitochondria.

   • Contains four redox active metal centers.

   • Molecular light excitation accelerates the rate of electron transfer that increases the capacity of mitochondria to generate ATP [83, 86].

   • Increased ATP results in increased energy available for that cell’s metabolic processes.

3. Increase of nitric oxide (NO) which leads to [85]

   • Alteration of cell activity

   • Increase cell membrane permeability to calcium and other ions.

2.4.2.4.3.4.1.1.2 Secondary responses

LLLT affects:

• RNA and DNA synthesis [82, 83, 84, 85]

• Cell proliferation

• Release of growth factors

• Increase in collagen synthesis by fibroblast

• Change in nerve conduction

• Release of the neurotransmitter.

2.4.2.4.3.4.1.2 Cellular effect of LLLT

Several studies in the literature have shown that LLLT increases fibroblast proliferation and the quantity of osteoid tissue [87, 88, 89]. The first effect is stimulation of cellular proliferation, especially nodule-forming cells of osteoblast lineage [87]. The second effect is stimulation of cellular differentiation, especially to committed precursors, resulting in an increase in the number of differentiated osteoblastic cells and an increase in bone formation [87, 89].

The effects of the LLLT particularly on bone modeling-modeling/remodeling regarding OTM occur through its effect on the following: [90].

1. Osteoclast activity

2. PDL regulations

3. Osteoblast activity

4. Blood vessels

2.4.2.4.3.4.1.2.1 LLLT and osteoclast activity

The LLLT effect on osteoclasts is not clear. Dozens of cytokines, hormones, and peptides have been proven to play a role in bone turnover. A review of the literature yields a number of reports indicating how some of the factors involved in osteoclast regulation may be affected by LLLT [91].

LLLT facilitates the differentiation and activation of osteoclasts are via:

• RANK expression

Activation and maintenance of osteoclastic activity is under control of binding of RANKL with RANK [76]. When RANKL docks with RANK, preosteoclasts differentiate and become osteoclasts. Studies have observed a greater number of RANK and RANKL positive cells in laser-treated groups than in the nonirradiated groups [76].

However, another study [92] has shown that LLLT indirectly inhibited osteoclast differentiation by down regulating the RANKL/OPG mRNA ratio in osteoblasts and promoting proliferation and differentiation of osteoblasts, thus contributing to bone modeling/remodeling.

• 2-Macrophage colony-stimulating factor (M-CSF) and its receptor system (colony-stimulating factor-1 receptor; c-fms) which is essential for osteoclastogenesis to stimulate osteoclast precursor cells and mature osteoclasts [93].

• OPG regulation

RANKL binds to the decoy receptor osteoprotegerin (OPG), decreasing the amount of RANKL available for binding to RANK. Thus, OPG decreases the differentiation and activation of osteoclasts. It was found that the level of OPG expression between the laser and control group did not vary. However, a significant increase of the cytokine with LLLT application was reported. Recently, it has become clear that LLLT increases tooth movement by activating the RANK/RANKL/OPG system, which reflects the differentiation level of osteoclasts and is required for bone remodeling [76, 94].

• Transforming growth factor beta 1(TGF-β1) expression

TGF-β1 is integral in the differentiation and in maintaining the function of osteoclasts. It was found that sufficient expression of (TGF-β1) upregulates RANKL levels in the absence of osteoblasts, while excessive amounts of TGF-β1 in the presence of osteoblasts decrease RANKL upregulation [53, 93].

• Cyclooxygenase 2 (Cox-2) regulation

Cox-2 is the rate-controlling enzyme in the conversion of arachidonic acid to ProstaGlandins Enzyme (PGE), which is essential in osteoclast regulation. Several authors have shown that both Cox-2 and PGE-2 upregulate RANKL and inhibit OPG levels [95, 96, 97].

2.4.2.4.3.4.1.2.2 PDL regulation

During OTM mechanical forces induce biochemical changes in the microenvironment of the PDL that accelerates orthodontic tooth movement [98]. LLLT makes changes in the process of PDL organization by affecting the two main components of this process via:

• Increased fibronectin expression

Both osteoblasts and fibroblasts produce fibronectin. During PDL reorganization, fibroblast is crucial for adhesion, growth, cell migration, and differentiation. It is crucial for the healing of wounds. By facilitating phagocytic cell migration and boosting the presence of osteoclast-like cells, fibronectin may thus have numerous functions in PDL and bone turnover [99, 100, 101]. From day one, LLLT groups showed increased fibronectin expression and collagen type 1 turnover as compared to controls. This may be the case because fibronectin stimulates RANKL overexpression, which causes osteoclast differentiation [95, 102].

• Increased collagen type 1 turnover

The increased rate of collagen type 1 degradation and reorganization may also assist in minor increases in OTM rate as it is the main component of PDL [53, 98].

2.4.2.4.3.4.1.2.3 LLLT and osteoblastic activity

The biostimulatory effect of LLLT on osteoblasts was described via: [102, 103, 104, 105].

• An increase in bone matrix production.

• An increase in DNA replication and proliferation of the osteoblasts.

• Promotes osteoblast differentiation and osteogenesis.

• Augment the osteogenic potential of growth-induced cells.

• Stimulate the rate of growth and differentiation of the human osteoblast-like cells.

2.4.2.4.3.4.1.2.4 LLLT and tissue vascularity (blood vessels)

Vascularization is essential for the movement of orthodontic teeth. Key biological components go through the blood arteries to the locations of bone resorption and deposition regardless of the type of bone resorption, whether frontal or undermining. Other phagocytic cells pass via capillaries with developing osteoclasts and help in tissue modeling and remodeling in addition to bone modeling. In comparison with controls, histological sections after 7 days after healing on the laser experimental sides showed faster deposition of bone matrix as well as nascent vascularization [102, 103].

2.4.2.4.3.4.2 Clinical studies assess the effect of LLLT on OTM rate

Many studies adopted Ga-Al-As diode laser emitting a wavelength of 610–960 nm of infrared light application in extraction cases during canine retraction with retraction force at least 150 g. Most of studies demonstrated that the application of the laser accelerated the velocity of tooth movement. However other studies conducted results appeared to have no significant difference between the laser and the control group in the studies conducted [29, 79, 80, 88, 98, 102, 103, 106, 107, 108, 109, 110, 111].

Upon considering the results of previous investigations, the “18.4 J” of energy applied was found to be higher than the “2.0–8.0 J” range of energy levels and other studies had applied to demonstrate an enhanced tooth movement in human subjects. The studies generally found that LLLT can be effective at stimulating OTM and inducing an increase of up to 33% [111]. In other study, a double-fold increase in the rate of tooth movement was observed when using a 8.0 J Ga-Al-As diode laser was irradiated while reducing 70% of accompanying pain during tooth movement [102], while other study reported that LLLT has no effect on pain reduction [98]. The optimum dose of laser energy required to facilitate the tooth movement in human subject appeared to be different against the dose recommended in animal subjects [88].

A systematic review has been conducted on 2020 concluded that it is strongly advised to express and compare laser dosage in terms of total joules applied each month rather than the previously utilized J/cm². Furthermore, the earlier recommendation that lower energy densities (2.5, 5, and 8 J/cm²) are more effective than 20 and 25 J/cm2 is deceiving [112].

2.4.2.4.3.4.2.1 Cause of variable results upon LLLT effect

Thus, there were many contradictory results regarding the efficacy of LLLT, possibly due to a non-standardized LLLT application protocol with variability in wavelength and fluency of those investigations. The clinical studies used a wide range of wave lengths varying from 610 nm to 960 nm. It seemed interesting to identify the motives behind the choice of wavelength by the different authors. The studies’ findings are equivocal and cannot be generalized to the general population; hence, well-structured research is needed to reduce bias and get a better understanding of the LLLT influence on the acceleration of OTM [4, 66, 90, 94].