DIFFERENT MODALITIES FOR ACCELERATING ORTHODONTIC TOOTH MOVEMENT: A REVIEW OF STUDIES.

of mesialization of the 1st molar 1.6 times after administration of a of 0.25 ΜG g b.w. into the subperiosteal

It is hence necessary to affect the surroundings of the tooth that ensure its stable position in the neutral zone − the alveolar bone. Tooth movement takes place with the simultaneous cooperation of osteoclasts in the pressure zone (which leads to resorption) and osteoblasts in the pulling zone (the apposition process). An imperative role is also played by periodontal ligaments, which, while acting as a force absorber, also play the part of specific receptors associated with the sympathetic system. Methods of accelerating tooth movement are based on stimulating biological tissue response, i.e., enhanced metabolism and accelerated bone remodeling. On the basis of the level of invasiveness, the methods encountered in the scientific literature can be divided into conservative methods and those based on surgical intervention. 11 Recently, numerous methods have been proposed to enhance the rate of orthodontic tooth movement so that faster and better treatment options can be provided to the patients. The aim of this article is to enumerate and discuss different methods to accelerate orthodontic tooth movement and also to discuss advantages and shortcomings of each method. Methods to accelerate orthodontic tooth movement can be discussed under the following categories:

Conservative Methods:-
The application of pharmacological agents At the cellular level, the predominance of osteoclast activity over osteoblasts is responsible for bone resorption. It occurs as a result of the intensification of the inflammatory process in the periodontal and connective tissue of the gum. Mature osteoclasts can be stimulated by pro-inflammatory signals coming from perio-pathogens, fibroblasts, macrophages or Th lymphocytes. Another pathway of bone resorption is based on the mechanism of osteoblast and cell-precursor differentiation towards osteoclasts. This is an effect of the nuclear factor kappa B receptor (RANK) system and the receptor activator of nuclear factor kappa-Β ligand (RANKL) competing with osteoprotegerin (OPG). 1

Growth Hormone
Growth hormone (GH), also called somatotropin, is secreted by the anterior lobe of the pituitary gland. It has a stimulating effect on bone growth and remodeling, and a deficiency results in pituitary dwarfism. The action of GH is based directly on increases in the proliferation and differentiation of osteoblasts, as well as on induction of protein synthesis and mineralization. Ribeiro et al. assessed the modifying effect of growth hormone on the pace of tooth movement during experimental orthodontic treatment in rats. In their study, individuals from the experimental group were administered daily subcutaneous doses of growth hormone of ≈ 0.033 mg/kg, analogous to the dose used in humans. A day after the 1st dose was administered, a nickel-titanium spring was fixed between the incisor and the right 1st molar, exerting a force of 30 g. Growth hormone accelerated bone resorption (in the experimental group the highest number of osteoclasts was recorded as early as on the 3rd day, which was twice as high as in the control group on day 7), but it also delayed angiogenesis. This suggested that the activation of a device should be less frequent after GH administration. There are even recommendations to begin orthodontic therapy 12-24 months after GH administration, because only then will somatotropin stimulate the process of bone formation. As GH reduces the synchronization between resorption and bone apposition, this is not a method of high potential clinical relevancy. 5 Parathormone Parathormone (PTH) is a compound secreted by the parathyroid gland which binds to receptors on osteoblasts, activating them and leading to the expression of insulin-like growth factor 1 (IGF-1; somatomedin). This results in the proliferation of osteoblasts and, with the participation of the RANK ligand, osteo-clastactivation. Depending on the frequency of administration, PTH may stimulate bone formation (intermittent therapy) or its resorption (exposure longer than 1-2 years). Two 12-day studies in rats confirmed that intermittent administration of PTH accelerated the mesialization of the 1st molar 1.6 times after administration of a dose of 0.25 ΜG/100 g b.w. into the subperiosteal area and 1.4 times as a result of subcutaneous administration of 4 μg/100 g m.c. However, another study by the same authors does not confirm the efficacy of intermittent therapy. Long-term research on the superiority of this method over other protocols is needed, as well as clinical trials. Nevertheless, it is important to consider chronic PTH intake when planning orthodontic treatment, e.g., in cases of severe osteoporosis. 1,11,18 Vitamin D Another agent that may affect tooth movement is vitamin D. 1,25-dihydroxycholecalciferol is the most active metabolite of this vitamin. It mainly has an anabolic effect on the bone tissue (to a small extent also catabolic). Similarly to PTH, subperiosteal administration of vitamin D enhances the activity and proliferation of osteoblasts. These properties prompted researchers to design animal experiments attempting to modify the course of orthodontic treatment. Collins et al. used calcitriol dissolved in DMSO (dimethylsulfoxide) − a compound that readily penetrates cell membranes, as well as has a high solubility coefficient for vitamin D) − administered daily into the periosteum. After 3 weeks, the retraction range of the canines was 60% higher compared to the control group. 7,8 Other researchers came to similar conclusions, this time testing the action of this vitamin on rats. They noticed an increased number of both osteoclasts and osteoblasts. Kawakami and Takano-Yamamoto emphasized the continuation of intensified remodeling during the retention period as well. In turn, Kale et al. observed that distalization of the maxillary incisors increased by 23%. In a few clinical trials, acceleration of orthodontic tooth movement was also demonstrated. After a daily oral dose of 0.25 μg of vitamin D, the mean difference in the retraction movement between the experimental group and the control group (who underwent orthodontic therapy without supplementation) was 1 mm/60 days. However, the use of a very low dose of the supplement in the study appears to be questionable (10 IU vs the daily recommendations of 1000-2000 IU). 19

Thyroxine
Thyroxine administration is a recommended form of hypothyroidism treatment. It increases bone remodeling and stimulates resorption, which contributes to a decrease in bone density. This is probably due to the increased concentration of interleukin 1 (IL-1), which stimulates the formation of osteoclasts and the resorption process. Animal studies confirm accelerated tooth movement after administration of this substance. Seifi et al. observed 0.45 mm of movement after 21 days in their experimental group, compared to 0.23 mm in the control group. Additionally, they detected cumulative effects of concomitant administration of thyroxine and prostaglandine E2 (0.74 mm of movement). However, Shirazi et al. noticed much less root resorption after thyroxine-assisted orthodontic treatment. Despite the lack of clinical trials, the presence of metabolic diseases related to the thyroid gland should be taken into consideration when planning orthodontic treatment. In cases of hypothyroidism it is recommended to activate the device less frequently,Where as for patients with hyperthyroidism, a longer retention period is recommended .3

Beta 2-Adrenergic Agonist
There is a very specific periodontal microenvironment between the tooth and the bone that requires further description. It consists of collagen fibers, cells and tissue fluid acting as a force absorber. The ligaments are strongly innervated: they contribute to the transmission of pain, modification of the immune response and bone remodeling. During orthodontic treatment mechanical force acting on the tooth is transmitted to these ligaments. Periodontal cells stimulate the biological response (e.g., by increasing the amount of Y-neuropeptide-containing fiber, substance P or calcitonin gene-related peptide). This is confirmed by the impossibility of moving ankylotic teeth, which are deprived of periodontal fibers due to direct connection with the bone. Periodontal ligaments are formed from the cranial neural crest differentiating in embryonic stem cells. Due to their origins, they express Β2-adrenergic receptors and, through the RANK receptor system, stimulate osteoblasts to undergo osteoclastogenesis. The available studies involving Β2-adrenergic agonists are based on direct evidence (stimulation of receptors with agonists, e.g., isoproterenol) or indirect observations (similar inhibition of the sympathetic system after using propranolol). Takeda et al., using isoproterenol, induced an osteoclastogenic response in mice. According to Kondo et al., by inhibiting the sympathetic system with the butaxamine, bone loss was limited and tooth movement slowed down. Kondo et al. also made intraperitoneal injections of propranolol, isoproterenol or (in the control group) saline solution, and blockages or stimulations confirmed their thesis. More invasive tests on rats were performed by Cao et al. After performing ganglionectomies of the upper cervical ganglion, they noted a decrease in osteoclast differentiation and limited tooth movement. Yamashiro et al., in an animal model of experimental tooth movement, noted a lack of significant changes in bone remodeling after transection of the lower alveolar nerve. In conclusion, despite the presence of many experiments related to Β2-adrenomimetics, one cannot overlook the fact that there are no clinical trials that provide significant scientific evidence. 4,6,10

Physical Stimuli
Studies on the acceleration of teeth movement describing stimuli which increase the metabolism of tissues were investigated. The mechanisms of the most of them are not fully understood, but there is considerable evidence of their beneficial effects.

Electromagnetic Fields
Electromagnetic fields have a proven effect on cell membrane permeability. They can be divided into static magnetic fields (SMF) and pulsed electromagnetic fields (PEMF). Both types have been used in general medicine for many years. A SMF can contribute to the healing process after an osteotomy, can stimulate bone remodeling, or prevent bone volume decrease after surgical intervention or implantation. In the field of orthodontics, it has been used for many years as an element supporting active therapy or even as an independent procedure. It may be of certain clinical benefit during space closure, intrusion, forced extrusion of impacted teeth, and palatal expansion. An analysis of the few available animal studies concludes that in order to accelerate tooth movement, a field with a flux density of 460 mT should be used. Sakata et al. came to this conclusion analyzing the previous experiment of Tengku et al., who, while using the intensity of 10 mT, did not observe clinically satisfactory results. 9 A PEMF, by stimulating osteoblasts to proliferate and differentiate, as well as increasing the production of alkaline phosphatase and regulating calcium metabolism, can improve the treatment of bone fractures, osteonecrosis and osteoporosis, among other things. According to Bassett's research, therapeutic application of magnetic fields results in the creation of cellular tension similar to that which is induced during mechanical deformation of the bone (e.g., during the movement of the teeth). Studies on a rat model have shown that the support of active orthodontic elements operating with a force of about 20 g, both using a PEMF of 1.8 mT (or 1.5 mT) and a Nd-Fe-B magnet (neodymium), increases the distance a tooth can be moved. Stark and Sinclair and Showkatbakhsh et al. also confirmed the accelerating action of PEMF. In both cases, they observed positive effects. However, the authors pointed out that due to differences in size and physiology, predicted results on the human body should be extrapolated with caution. Information regarding the lag phase in orthodontic tooth movement (the phase of clearing hyalinized fibers from the pressure zone) is also important. It can be hypothesized that electromagnetic field therapy can shorten the lag phase (due, among other things, to earlier formation and removal of hyalinized tissue). 7,9 Vibrations Rubin et al. have proven that vibrations increase the remodeling rate and the overall reconstruction of the long bones -a phenomenon used in the prevention of osteoporosis. In addition, by comparing the effects of cyclic and static forces in experiments on animal models (cranial sutures and the periosteum of the long bones), an improvement in bone formation and an increase in orthodontic tooth movement was observed. Initial clinical trials have shown promising results. Dubravko et al. used the AcceleDent device (Ortho Accel Technologies, Bellaire, USA) to generate a vibration of 0.25 N and a frequency of 30 Hz. It was possible to accelerate the distalization of canines with skeletal anchorage by 48.1% compared to the control group (1.16 mm vs 0.79 mm/month). Other reports have also confirmed the accelerating effect of vibrations. This time, the source of the stimuli was electric toothbrush massage for 15 min a day (a frequency of 125 Hz). Within 3 months, a 2.85 mm distal axial movement of the canines was obtained (37.7% greater than in the control group). Those authors additionally investigated the concentration of IL-1β in fluid collected from the gingival pocket, which, as a factor stimulating the expression of RANKL, can be a good indicator of the effectiveness of orthodontic movement. On the pressure side, the concentration of the cytokine in the study group was on average more than 6 times higher than in the fluid collected from the control group. Contrary to expectations, acceleration was not confirmed by studies in mice in which orthodontic forces were applied to the 1st molars and low frequency vibrations (5, 10 and 20 Hz) were used. Furthermore, the latest randomized clinical trials call into question the chances of significantly shortening the time of orthodontic treatment by administering vibrations. 2,7.19

Photobiomodulation
This technique can be characterized by a very limited invasiveness. It involves the exposure of tissues to the effects of red light of a therapeutic wavelength (600-1200 nm). These wavelengths reduce absorption of the light by hemoglobin and water and allow it to reach the deeper soft tissue and the alveolar bone. The resulting stimulation may have potentially positive effects on the production of adenosine triphosphate (ATP). ] On the other hand, increasing the activity of cells leads to increased bone metabolism in situ, which creates favorable conditions for the movement of teeth. Therapy with light can be divided into 2 basic types: low-intensity lasers (LIL), producing coherent light, and light-emitting diodes (LED), which are sources of incoherent light. There are no publications regarding the superiority of one above the other. What is more, most authors agree that the cellular response depends primarily on the wavelength and the dose of light, not on its source. Only Fujita et al. noted more favorable results in LIL therapy, and Vinck et al. found that an LED source creates more favorable conditions for cell growth in green light. Numerous studies on this subject can be found in the literature, on both animal and clinical models. Most of them indicate a significant increase in the speed of tooth movement. Inthese studies gallium-aluminum-arsenide (Ga-Al-As) lasers were used, and the length of light wave was on average 820 nm. The challenge was to determine the optimal 1401 energy dose. Goulart et al. achieved acceleration as a result of a combined dose of 5.25 J/CM2, but noted that increasing it to 35 J/cm2 could have the opposite effect. This thesis was confirmed by several researchers, including some studies applying irradiations of 100 mW.61-70 Animal studies have adopted a methodology focusing on determining remodeling efficiency, the RANK/RANKL system, and the expression of fibronectin and type I collagen. 6,8 In addition to standard tooth movements, Saito and Shimizu were able to accelerate bone regeneration after suture opening during expansion of the palate in rats. Youssef et al., after 6 months of research on a group of 15 adults, achieved an almost 2-fold acceleration of canine retraction. Nahas et al. investigated the effects of the Ortho-Pulse device (Biolux Research Ltd., Vancouver, Canada) in patients with Little's irregularity index in the range of 2-10 mm. Satisfactory results were obtained in the research group after an average of 68.3 days (compared with 87.8 days in the control group), which shortened the treatment time by 22%. Acceleration has also been reported in a few randomized clinical trials. Nevertheless, Marquezan et al., during an experiment on an animal model, despite an increased number of osteoclasts on the pressure zone side, did not notice an increased dental shift macroscopically. Chung et al. came to a similar conclusion after observing 11 patients for 3 months. To sum up, due to the differences in the protocols of the experiments conducted, further research is needed, focusing, among other things, on harmonizing the radiation dose. 9,12

Clear Aligners and Self-Ligating Brackets
In the literature, only a few studies can be found analyzing the acceleration of the movement of teeth using clear aligners and self-ligating brackets. It should also be noted that research based on histological evidence is lacking. Conclusions can be drawn based only on the differences in therapy duration and cases assessed using various indices, such as the peer assessment rating (PAR) or the objective grading system (OGS). Gu et al. found the Invisalign system (Align Technology Inc., San Jose, USA) to be advantageous in correcting minor orthodontic defects; the duration of treatment with the same effects was 30% (5.7 months) shorter compared to fixed braces. Buschang et al. reached similar conclusions: in a study of 150 patients with incisor crowding under 5 mm (the study group), they noted that the duration of therapy was reduced by 5.5 months. 16 However, despite shorter treatment and less frequent visits, they point out that aligner therapy is much more expensive and requires more experience. On the other hand, Hennessy et al. did not notice a difference between the length of the treatment of mandible incisor crowding with the Invisalign system and with a fixed labial appliance. In summary, the use of clear thermoplastic aligners, despite their presence and growing popularity in orthodontic clinics, requires further research in terms of accelerating the movement of teeth. Self-ligating brackets are also worth mentioning. The 1st brackets of this type were created by Stolzenberg over 70 years ago.
The aim was to reduce the friction between the arch and the bracket, which is increased by ligatures (both elastic and metallic). According to some researchers, reducing it improved the effectiveness of the "sliding mechanism" used during tooth rotation, correction of angulation and closing spaces. It does not affect bone remodeling, but only changes the distribution of forces that the orthodontist uses during treatment. In addition, despite manufacturers' assurances of shorter treatment times, numerous studies have reported the opposite, detecting no significant differences between the duration of active therapy with the use of conventional and self-ligating devices. 17

Surgical Methods
The surgical technique has been documented in many case reports. It is a clinically effective technique used for adult patients, where duration of orthodontic treatment may be critical. Periodontal ligament (PDL) and alveolar bone remodeling are the important parameters in tooth movement and bone turnover is known to increase after bone grafting, fracture, and osteotomy. Several surgical approaches that have been tried in order to accelerate tooth movement are Corticotomy and Piezocision technique. The idea of surgical acceleration came into being after the introductionof Regional Acceleratory Phenomena (RAP) by Frost in 1983. RAP is a local response to noxious stimulus, by which tissue forms faster than the normal regional regeneration process. This phenomenon causes healing to occur 2-10 times faster than normal physiologic healing by enhancing the various healing stages. 9

Corticotomy
It was first tried in orthodontics by Kole. Conventional corticotomy is one of the surgical procedures that is commonly used, in which only the cortical bone is cut and perforated but not the medullary bone. This will reduce the resistance of the cortical bone and accelerate tooth movement. It was suggested that bony blocks were created as a result of the corticotomy, hence causing faster tooth movement. The conventional corticotomy procedure involves elevation of full 1402 thickness muco periosteal flaps, bucally, followed by placing the corticotomy cuts using either micro motor under irrigation, or piezo surgical instruments. This can be followed by placement of a graft material, wherever required, to augment thickness of bone. 4 Until 2001, the "bony block" concept prevailed as a misconception. However, Wilcko et al reported that tooth movement was not the result of bony block, but rather a process of transient remineralization/demineralization which is a concept of reversible osteopenia in the bony alveolar housing consistent with wound healing pattern of RAP. He also introduced the term "bone matrix transportation and developed patent techniques which were called Accelerated Osteogenic Orthodontics (AOO) and Periodontal Accelerated Osteogenic Orthodontics.
Modification of RAP was done by adding bio-absorbable grafting material over the injured bone to enhance healing.

Advantages
1. Corticotomy procedure causes minimal changes in the periodontal attachment apparatus. 2. It has been proven successfully by many authors to accelerate tooth movement. 3. Bone can be augmented; thereby preventing periodontal defects. 7

1403
Small harmful stimuli (such as Shallow bone incisions) activate the RANK/RANKL system. In "weakened" bone tissue, 10-50 times faster remodeling is expected. This effect lasts for about 4 months (though it can last up to 6-24 months), with peak efficiency reached 1 or 2 months after surgery. Due to the nature of the surgery, which involves a high risk of infection, antibiotic protection is vital. Only local anesthesia is required. The field of the procedure depends on the defect: vertical incisions are made between the roots of the teeth, horizontally, 2-3 mm above the apices, in order not to damage the bundles.
The advantage of the method lies in the creation of a more stable anchorage, not involving teeth/arches in the procedure. The brackets of the fixed appliance are bonded before the surgery. The cuts, after earlier retraction of the mucoperiosteal flap, can be made with traditional rotational tools or a piezoelectric knife. Dibart et al. recommend the use of the latter, due to limited traumatization of tissues, greater precision of execution, and more extensive bone demineralization, which induces prolonged RAP. To avoid interfering with the bone remodeling process, non-steroidal anti-inflammatory drugs (NSAIDs) should not be administered. Initially (in the first 3-7 days) the pain can severely affect the patient's well-being. Tooth brushing should be neglected for a week. An alternative is to rinse the mouth with an antiseptic solution (e.g., chlorhexidine). After this period, the 1st activation of the braces can be performed. It is important that during the demineralization of the bones, the patient appears regularly for frequent visits. 1,2,12,16

Piezocision
One of the recent techniques inaccelerating tooth movement is the Piezocision technique. Dibart was amongst the first to apply thePiezocision technique which starts with primary incisionplaced on the buccal gingiva, below the interdental papilla, as far as possible, in the attached gingiva using a No.15 scalpel. These incisions need to be deep enough so as to pass through the periosteum and contact the cortical bone. Next, using ultrasonic instrumentation (they used a BS1 insert Piezotome), perform the corticotomy cuts to a depth of 3 mm through the previously made incisions. At the areas requiring bone augmentation, tunneling is performed using an elevator inserted between the incisions, to create sufficient space to accept a graft material. No suturing is required except for the areas where the graft material needs to be stabilized. Piezocision technique does not cause any periodontal damage as reportedby Hassan. The study by Keser concluded that this technique can be used with Invisalign which leads to abetter aesthetic appearance and also the treatment time is shortened. Piezocision is a promising toothacceleration technique because of its various advantageson the periodontal, aesthetic, and orthodontic aspects.

Micro-Osteoperforations
This is another treatment modality based on the RAP. The goal is to further minimize soft tissue damage. Perforations are made in the bone through the mucous membrane, with the aim of accelerating orthodontic movement. Microosteoperforations can also be combined with standard corticotomy or the PAOO technique. The device used during the treatment was designed by Propel Orthodontics (Ossing, USA). It is intended for single use only. It perforates both the attached gingiva and the mucous membrane. Clinically, the use of micro-osteoperforations significantly increases the expression of cytokines, which leads to a 60% shorter treatment time compared to a control group, and 2.3 times faster 1404 retraction of canines. The procedure itself is described as effective, convenient, and less invasive than standard corticotomy. 2,5,7 Corticotomy and other attempts at surgical acceleration of tooth movement are documented in a large number of scientific publications. Despite the different levels of invasiveness, they have similar effectiveness, which was confirmed in a comparative study by Librizzi et al. It can be assumed that this is the effect of the same mechanism of action (inducing the RAP). Experiments conducted on an animal model show both a shorter therapy time and increased remodeling occurring within the cancellous bone. Similar results were obtained during the treatment of mild crowding (a study on 24 patients resulted in a 47% shorter treatment time), orthodontic extrusion of palatally impacted canines (

Combined Methods
Considering the different mechanisms of action of conservative and surgical methods, the question arises: Would the combination of both prove even more efficient? Referring to this hypothesis, Kim et al. conducted a study combining cortical bone incision (also referred to as corticision) and radiation. The experiment involved 12 dogs divided into 4 groups: a control group (only orthodontic force was used), a group undergoing photobiostimulation, a group undergoing surgical treatment, and a group in which both of these methods were implemented. In the groups involving the surgical procedure, incisions were made near the 2ND maxillary premolars (for the purpose of their mesialization after the extraction of the 1st premolars). A diode laser with a wavelength of 808 nm was used as the source of photobiostimulation. 7,8,9 Contrary to expectations, the group covered by both treatment methods showed less acceleration than the groups under going each treatment separately. Moreover, with in 8 weeks after the procedure, the dental movement in the group exposed to both methods was comparable to the control group (in which only orthodontic forces were used).
Considering the regenerative effect of light irradiation, it can be assumed that the laser significantly accelerated bone healing and thus led to the elimination of the RAP. The available literature also describes 2 cases in which corticotomy and Smiletech polyvinyl overlays (Ortodontica Italia, Rome, Italy) were used. Cassetta et al. described the therapy of 2 patients with moderate crowding (the 1st with class I, the 2ND with class II). The treatment was completed with a satisfactory effect after 2 months (in the class I patient) and after 8 months (in the class II patient). However, attention should be paid to the low power of scientific evidence (no control group; only a case report) and the possible bias of the conducted study. 6.17

Conclusions:-
The contemporary literature presents various methods of accelerating tooth movement during orthodontic treatment, but a significant number of them, especially those using pharmacological agents, are supported by rather limited scientific evidence due to the fact that randomized clinical trials are rarely encountered. The methods using physical stimuli, in spite of the larger number of published trials, can prove difficult to apply in everyday practice due to the use of expensive and specialized equipment and the need for regular and repeated administration of specific agents. Surgical methods are currently the most soundly evidenced, and could be described as methods of documented efficacy. Unfortunately, they are associated with significant (though constantly diminishing) invasiveness, exposing.