Evaluating the efficacy of platelet-rich plasma on orthodontic tooth movement rate: A systematic review and meta-analysis.

BACKGROUND: The main objective of this study was to evaluate the effect of autologous platelet-rich plasma (PRP) on acceleration of the orthodontic tooth movement and assess the evidence based on the available literature. METHODS: The trial was registered and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic databases including PubMed, Cochrane, Scopus, Central Register of Controlled Trials, and Google Scholar were searched for randomized controlled studies of PRP on the rate of tooth movement. The search was restricted to articles published in English between January 2000 to 31 December 2023. The search was completed by two reviewers independently and the risk of bias was evaluated using the Cochrane Risk of Bias tool (RoB 2.0) and meta-analysis was performed. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was done to determine the certainty of evidence. RESULTS: Thirteen studies were included in the systematic review and 10 were included in the quantitative analysis. A random-effects model for meta-analysis of seven studies evaluating the rate of canine retraction revealed a statistically significant increase in the rate of orthodontic tooth movement of 0.38 mm/month in 1 month (121 patients; 95% confidence interval [CI] 0.27-0.49; I2 = 35%; P < 0.001) which decreased to 0.09mm/month in the fourth month (80 patients; 95% CI 0.02-0.17; I2 = 0%; P < 0.02). Three studies that considered en masse retraction revealed a mean difference of 0.36mm over 3 months (40 patients; 95% CI -0.23 to 0.94; I2 = 74%; P < 0.23). CONCLUSIONS: The study suggests that PRP application can accelerate tooth movement, but its effects decreased over 4 months. The results should be interpreted cautiously due to the study's inherent limitations.

Exploring biological mechanisms in orthodontic tooth movement: Bridging the gap between basic research experiments and clinical applications - A comprehensive review.

OBJECTIVES: The molecular mechanisms behind orthodontic tooth movements (OTM) were investigated by clarifying the role of chemical messengers released by cells. METHODS: Using the Cochrane library, Google scholar, and PubMed databases, a literature search was conducted, and studies published from 1984 to 2024 were considered. RESULTS: Both bone growth and remodeling may occur when a tooth is subjected to mechanical stress. These chemicals have a significant effect on the stimulation and regulation of osteoblasts, osteoclasts, and osteocytes during alveolar bone remodeling. This regulation can take place in pathological conditions, such as periodontal diseases, or during OTM alone. This comprehensive review outlines key molecular mechanisms underlying OTM and explores various clinical assumptions associated with specific molecules and their functional domains during this process. Furthermore, clinical applications of certain molecules such as relaxin, prostaglandin E (PGE), and interleukin-1ß (IL-1ß) in accelerating OTM have been reported. Our findings underscore the existing gap between OTM clinical applications and basic research investigations. CONCLUSION: A comprehensive understanding of orthodontic treatment is enriched by insights into biological systems. We reported the activation of osteoblasts, osteoclast precursor cells, osteoclasts, and osteocytes in response to mechanical stress, leading to targeted cellular and molecular interventions and facilitating rapid and regulated alveolar bone remodeling during tooth movement. Despite the shortcomings of clinical studies in accelerating OTM, this review highlights the crucial role of biological agents in this process and advocates for prioritizing high-quality human studies in future research to gain further insights from clinical trials.

SDF-1 involvement in orthodontic tooth movement after tooth extraction.

The stromal cell-derived factor 1 (SDF-1)/chemokine receptor type 4 (CXCR4) axis plays a key role in alveolar bone metabolism during orthodontic tooth movement (OTM). Herein, the effects of the SDF-1/CXCR4 axis on the regional acceleratory phenomenon (RAP) in OTM velocity and on changes in the surrounding periodontium after adjacent tooth extraction in rats were investigated. Six-week-old male Wistar/ST rats underwent left maxillary first molar (M1) extraction and mesial OTM of the left maxillary second molar (M2) with a 10-g force closed-coil spring. Phosphate-buffered saline, immunoglobulin G (IgG) isotype control antibody, or anti-SDF-1 neutralizing monoclonal antibody were injected at the M1 and M2 interproximal areas (10 µg/0.1 mL) for the first three days. Analyses were performed after 1, 3, and 7 days (n = 7). The results demonstrated a significant increase in SDF-1 expression from day 1, which was effectively blocked via anti-SDF-1 neutralizing monoclonal antibody injection. On day 3, the M2 OTM distance and the number of positively stained osteoclasts significantly reduced alongside a reduction in inflammatory markers in the experimental group. Our results demonstrated that serial local injection of the anti-SDF-1 neutralizing monoclonal antibody reduces M2 OTM, osteoclast accumulation, and localized inflammatory responses in an OTM model with tooth extraction-induced RAP.

The tooth movement efficiency of different orthodontic thermoplastics for clear aligners: study protocol for a randomized controlled clinical trial.

INTRODUCTION: With regard to the esthetics and comfort of orthodontic treatment, the requirement for removable clear aligners (CAs) is increasing. Unlike conventional fixed orthodontic appliances, CAs were made of thermoplastic film by thermoforming on the personalized dental models. The construction of orthodontic thermoplastic is a critical factor for orthodontic tooth movement (OTM). Polyethylene terephthalate glycol-modified (PETG) and thermoplastic polyurethane (TPU) are the most commonly orthodontic thermoplastics; however, the evidence of the differences between different orthodontic thermoplastic are limited to vitro environment and the evidence in vivo environment is not available. Therefore, this trial aims to provide reliable evidence for orthodontists' personalized treatment plans whether the two most commonly used orthodontic thermoplastics of PETG and TPU have differences in the efficiency of OTM. METHODS AND ANALYSIS: This randomized controlled clinical study will recruit 44 orthodontic patients for orthodontic treatment. All the subjects will be randomized into two groups (PETG and TPU, n = 22 for each group). In the first stage (M0 to M1), clear aligners will be made of two orthodontic thermoplastics and move the maxillary first or second premolars 2 mm. In the second stage, patients will take the standard orthodontic treatments. The primary outcome will be the efficiency of clear aligners made of different materials on the digital models. The secondary outcome will be the efficiency of clear aligners made of different materials on the cone-beam computed tomography (CBCT). The efficiency will be calculated through the superimposition of the digital models and CBCT. DISCUSSION: The results from this trial will serve as evidence for orthodontists and manufacturers and clarify whether the difference in orthodontic thermoplastics significantly impacts the efficiency of OTM. TRIAL REGISTRATION NUMBER: ChiCTR2300070980. Registered on 27 April 2023. https://www.chictr.org.cn/showproj.html?proj=186253.

Parameter identification for the simulation of the periodontal ligament during the initial phase of orthodontic tooth movement.

The paper is concerned with simulation of the periodontal ligament response to force in the initial phase of orthodontic tooth movement. This is based on two previous investigations, a in vitro experiment with specimens of porcine mandibular premolars and a in vivo experiment on human upper first incisors. For the curve fit of the in vitro experiment a model function, assuming viscoelasticity, was introduced. The viscoelastic model function was augmented by a ramp rise time term, to account for observed dependence of the response on actuator velocity, and a previous load history term, to account for the effect of the previous tests on the current test. The correlation coefficient of a curve fit for all tests grouped together was R2=0.98. Next, a curve fit of the in vivo experiment was done. Good correlation was found for a simplified model function, without viscoelastic term (R2=0.96). For both tests, in vitro and in vivo, the ramp rise time term improved correlation. A finite element model of the specimen of the in vitro experiment was created. For the PDL a hyperelastic constitutive model for compressible material was used and model parameters were identified. The present work indicates that the macroscopic response of the periodontal ligament to an external load can be simulated with a poro-visco-hyperelastic model. The simulation showed that poroelastic behaviour will gradually cease when viscoelastic relaxation progresses. This followed also from dimensionless analysis. As a consequence, for slow loading, or if initial response to fast loading is not of interest, a visco-hyperelastic model may suffice. To identify parameters of the finite element model several optimisation problems were solved. A model function, which can be regarded as a reduced order model, allowed a full factorial experiment (analysis) at low cost, to identify initial parameters. The thus found parameters were further refined with an optimum interpolation meta-model. That is, for limited number of parameter combinations the response was simulated with the finite element model and a refined parameter study was conducted by means of optimal interpolation. The thus found optimal parameters were verified by simulation with the finite element model. Optimal interpolation is computationally cheap, which allowed full factorial experiments at low cost.

Cytokine levels in gingival crevicular fluid samples of patients wearing clear aligners.

OBJECTIVE: The aim of this study was to assess & compare the changes in cytokine levels in GCF samples of patients wearing clear aligners. METHODS: GCF samples of 10 patients undergoing orthodontic treatment, for correction of lower anterior crowding with clear aligners, were collected on day 0, 1, 3, 7 and 21 using periopaper strips. The upper arch was taken as the control site. The samples collected were further analyzed using commercially available ELISA based kits. RESULTS: The mean levels of IL-1ß at day 0, 1, 3, 7 and 21 were compared between experimental and control sites using unpaired t-test and it was found that the levels of IL-1ß were significantly elevated on experimental site in comparison to control site. CONCLUSION: It was concluded from the study that elevation in levels of IL-1ß as a biomarker of orthodontic tooth movement reaches its peak after 24 h of force application. The clear aligners, as an alternative to conventional fixed orthodontic treatment, were found to be efficient in correcting mild to moderate lower arch crowding.

Stress Distribution and Collagen Remodeling of Periodontal Ligament During Orthodontic Tooth Movement.

Periodontal ligament (PDL), as a mechanical connection between the alveolar bone and tooth, plays a pivotal role in force-induced orthodontic tooth movement (OTM). However, how mechanical force controls remodeling of PDL collagenous extracellular matrix (ECM) is largely unknown. Here, we aimed to evaluate the stress distribution and ECM fiber remodeling of PDL during the process of OTM. An experimental tooth movement model was built by ligating a coil spring between the left maxillary first molar and the central incisors. After activating the coil spring for 7 days, the distance of tooth movement was 0.324 ± 0.021 mm. The 3D finite element modeling showed that the PDL stress obviously concentrated at cervical margin of five roots and apical area of the mesial root, and the compression region was distributed at whole apical root and cervical margin of the medial side (normal stress < -0.05 MPa). After force induction, the ECM fibers were disordered and immature collagen III fibers significantly increased, especially in the apical region, which corresponds to the stress concentration and compression area. Furthermore, the osteoclasts and interleukin-1ß expression were dramatically increased in the apical region of the force group. Taken together, orthodontic loading could change the stress distribution of PDL and induce a disordered arrangement and remodeling of ECM fibers. These findings provide orthodontists both mechanical and biological evidences that root resorption is prone to occur in the apical area during the process of OTM.

Cystathionine gamma lyase aggravates orthodontic root resorption in mice.

BACKGROUND: This study aimed to determine the contribution of cystathionine gamma lyase (CSE) to physiological and orthodontic root resorption in mice. METHODS: Mice genetically deficient in the CSE (CSE-/-), the dominant hydrogen sulfide (H2S)-generating enzyme in osteoclast were used in this study. Physiological and orthodontic root resorption was assessed with micro computed tomography (micro-CT) and scanning electron microscopy (SEM) in the mice at the age of 8-, 26-, and 52-week and in 8-week old mice following 1-, 2-, and 3-week orthodontic treatment, respectively. Hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP) staining were used for further determination of root resorption and the number of osteoclasts. The receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) level in surrounding alveolar bone of the maxillary first molar after 2-week orthodontic treatment was measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: Root resorption lacunae (RRL) gradually and significantly increased with age in wild type (WT) and CSE-/- mice. The CSE-/- showed less RRL compared with the WT group. At each time point of orthodontic treatment, the CSE-/- group had less RRL and osteoclasts than the WT group. The orthodontically induced RANKL/OPG mRNA expression in the periodontal tissue in the CSE-/- group was lower than that in the WT group. CONCLUSIONS: CSE contributes significantly to physiological and orthodontic root resorption.

Expression pattern of YAP and TAZ during orthodontic tooth movement in rats.

Orthodontic tooth movement (OTM) is a periodontal tissue remodeling and regeneration process that is caused by bio-mechanical stimulation. This mechanical-chemical transduction process involves a variety of biological factors and signaling pathways. It has been shown that the Hippo-YAP/TAZ signaling pathway plays a pivotal role in the mechanical-chemical signal transduction process. Moreover, YAP and TAZ proteins interact with RUNX family proteins via different mechanisms. To explore the regulation of the Hippo signaling pathway during periodontal tissue remodeling, we examined the upper first molar OTM model in rats. We examined YAP, TAZ and RUNX2 expression at 12 hours, 24 hours, 2 days (2d), 4 days, 7 days (7d) and 14 days (14d) after force application. Haemotoxylin and eosin staining, immunohistochemical staining and western blot analysis were used to examine the expression level and localization of these proteins. We found that YAP, TAZ and RUNX2 expression started increasing at 2d, YAP and TAZ expression was proportional to the orthodontic force applied until peaking at 7d, and at 14d the expression started to decrease. YAP and TAZ were observed in osteocytes, bone matrix and periodontal ligament cells during OTM. Furthermore, using double labeling immunofluorescence staining, we found that the increase in TAZ expression was associated with RUNX2 expression, however, YAP and RUNX2 showed different expression patterns. These results suggest that the Hippo-YAP/TAZ signaling pathway participates in periodontal tissue remodeling through various mechanisms; TAZ may adjust bone tissue remodeling through RUNX2 during OTM, while YAP may regulate periodontal cell proliferation and differentiation.

A review of biomarkers in peri-miniscrew implant crevicular fluid (PMICF).

BACKGROUND: The temporary anchorage devices (TADs) which include miniscrew implants (MSIs) have evolved as useful armamentarium in the management of severe malocclusions and assist in complex tooth movements. Although a multitude of factors is responsible for the primary and secondary stability of miniscrew implants, contemporary research highlights the importance of biological interface of MSI with bone and soft tissue in augmenting the success of implants. The inflammation and remodeling associated with MSI insertion or loading are reflected through biomarkers in peri-miniscrew implant crevicular fluid (PMICF) which is analogous to the gingival crevicular fluid. Analysis of biomarkers in PMICF provides indicators of inflammation at the implant site, osteoclast differentiation and activation, bone resorption activity and bone turnover. The PMICF for assessment of these biomarkers can be collected non-invasively via paper strips, periopaper or micro capillary pipettes and analysed by enzyme-linked immunosorbent assay (ELISA) or immunoassays. The markers and mediators of inflammation have been previously studied in relation to orthodontic tooth movement include interleukins (IL-1ß, IL-2, IL-6 and IL-8), growth factors and other proteins like tumour necrosis factor (TNF-α), receptor activator of nuclear factor kappa-B ligand (RANKL), chondroitin sulphate (CS) and osteoprotegerin (OPG). Studies have indicated that successful and failed MSIs have different concentrations of biomarkers in PMICF. However, there is a lack of comprehensive information on this aspect of MSIs. Therefore, a detailed review was conducted on the subject. RESULTS: A literature search revealed six relevant studies: two on IL-1ß; one on IL-2, IL-6 and IL-8; one on TNF-α; one on CS; and one on RANKL/OPG ratio. One study showed an increase in IL-1ß levels upon MSI loading, peak in 24 hours (h), followed by a decrease in 21 days to reach baseline in 300 days. A 6.87% decrease in IL-2 levels was seen before loading and a 5.97% increase post-loading. IL-8 showed a 6.31% increase after loading and IL-6 increased by 3.08% before MSI loading and 15.06% after loading. RANKL/OPG ratio increased in loaded compared to unloaded MSIs. CONCLUSIONS: Cytokines (mainly ILs and TNF-α) and RANKL/OPG ratio showed alteration in PMICF levels upon loading of MSIs as direct or indirect anchorage.

Local injection of carrageenan accelerates orthodontic tooth movement: A preliminary experimental animal study.

BACKGROUND: Orthodontic tooth movement (OTM) can be accelerated by increasing bone turnover. Carrageenan is a common food additive, which can induce inflammation. Hence, it might accelerate OTM. However, it has not been investigated to date. METHODS: This 2-phase preliminary animal experimental study was conducted on 28 Wistar rats. A pilot study on 5 mice was done to estimate the experimental dose of carrageenan. The first phase evaluated the effect of a 40µL carrageenan 1% injection on inflammation status in 7 rats versus 7 control rats, 6hours after the injection. The second phase examined the effect of the same dose of carrageenan on OTM speed during 21 days of incisor retraction in rat, in two groups: control (normal saline) and carrageenan (n=7×2). This sample size was pre-determined based on a priori power calculations. In phase II, osteoclastic activity was also evaluated, 21 days after the injection. The groups were compared statistically (α=0.05). RESULTS: Six hours after carrageenan injection, 1, 3, and 3 rats had inflammation scores of 3 to 1, respectively. Six hours after saline injection, 1 rat had a score of 1 and the remainder had no inflammation (P=0.0023, Mann-Whitney). Twenty-one days after saline and carrageenan injection, OTMs were 0.7±0.3 and 1.1±0.4mm, respectively, (P=0.053, Mann-Whitney). Twenty-one days after saline and carrageenan injection, mean osteoclast counts were, respectively, 4.87±1.849 and 7.143±1.727 per field (P=0.025, Mann-Whitney). CONCLUSION: Local injection of carrageenan can induce inflammation after 6hours. It can increase approximately 1.6-fold the speed of OTM, and increase the osteoclast count 1.5-fold after 21 days of space closure.

The change of FOXO1 expression during alveolar bone remodeling induced by orthodontic force / 医用生物力学

Objective To study the remodeling of alveolar bone and change in expression of forkhead box O1 (FOXO1) during orthodontic tooth movement (OTM) in rat, so as to preliminarily investigate the role of FOXO1 in alveolar bone remodeling induced by orthodontic force. Methods The rat OTM models were established and the left maxillary 1st molars were moved with force of 50 g. The rats were executed on the 1st, 3rd and 7th day of OTM, respectively. HE staining and immunohistochemical staining were used to observe the remodeling of alveolar bone in the inter-radicular region of the 1st molars and expression of FOXO1 at different time points during OTM. Results The 1st molars were constantly moved mesially under orthodontic force. There were more osteoclasts in the alveolar bone of OTM group than that in non-OTM group, and the osteoclasts on the 3rd day of OTM showed the highest activity. The number of active osteoblasts gradually increased in the inter-radicular region of alveolar bone under orthodontic force, with the enhanced osteoblast activity. Expression of FOXO1 in OTM group was elevated compared with non-OTM group. Most osteoblasts in alveolar bone during OTM were FOXO1 positive, and the expression of FOXO1 was gradually increased with the number of osteoblasts increasing. Conclusions Orthodontic force induces bone remodeling of alveolar bone in the inter-radicular region during OTM, and the change in FOXO1 expression may be related to alveolar bone remodeling during OTM.

Effects of icariin on orthodontic tooth movement in rats.

PURPOSE: Orthodontic tooth movement (OTM) is achieved through bone remodeling of the alveolar bone. Icariin, the active ingredient isolated from Herba Epimedii which is a traditional Chinese medicine (TCM) commonly used for osteoporosis treatment in China. The purpose of the study is to explore the effect of icariin on OTM in rats, and analyze the possible mechanism involved. METHODS: 48 rats were selected and divided into 2 groups: the control group and the experimental group. Rats in the experimental group were given 20 mg/kg/day icariin by intragastric administration, while the control group received the same volume solvent. All rats were placed a closed coil spring between their upper first molar and incisor, exerting a force of about 40 g to establish animal models of OTM. As the first molar moved mesially, a space between the first and second molar was created. The rats were sacrificed in batch on the 7th, 14th, 21st and 28th days after orthodontic treatment. The amount of tooth movement was measured, and histomorphometric analysis based on slices from periodontium adjacent to the maxillary first molars were used to observe new bone formation, bone resorption and quantify osteoclasts. KEY RESULTS: Icariin increased OTM (P<0.05) by 65.2%, 35.3%, 11.7% and 16.7% on day 7, 14, 21, 28 respectively compared with the control group. The number of osteoclasts in the icariin group showed a transient but sudden increase and then a persistent decrease. CONCLUSIONS: Icariin could accelerate OTM in rats through promoting bone remodeling of alveolar bone.

Impact of Bisphosphonate on Orthodontic tooth movement and osteoclastic count: An Animal Study.

Background : The aim of the current study is to examine the effect of systemically administered BP-Pamidronate, on Orthodontic Tooth Movement (OTM) along with osteoclastic quantification in New Zealand white rabbits. Materials & Methods : Twenty rabbits used in the study, were equally divided into 2 groups ; Group-1 as Control & Group-2 as Experimental. A sentalloy NITI closed coil spring (GAC International, USA) of 100 gram force, ligated between the lower first molar and the anterior most incisors of the rabbit has served as orthodontic force element. The BP- Pamidronate was administered at the dosage of 1.5 mg/kg body intra-peritonially, on the 1st, 7th and 14th day of the experiment. On the 21st day both group of animals were sacrificed, mandibles were dissected. The formed diastema between the 1st and 2nd molar was measured on the dissected mandibles using standard metric scale, which is considered as the OTM in the mesial direction. Next, the alveolar bone regions along with intact mesial surfaces were processed for histological investigation (osteoclastic count). Results : The student 't' test has been done to compare the mean values of molar tooth movement and osteoclastic count. Parameter :1 molar tooth movement has shown a significant difference between the control (3.750 ± 0.548 mm) and the experimental group (3.050 ± 0.556 mm) with calculated 'p' value (p-value <0.05) is significant at 0.0110 level. Parameter : 2 osteoclastic count has shown a significant difference between the control (13.335000 ± 0.735856 per square mm.) and the experimental group (11.426900 ± 1.49369 per square mm) calculated 'p' value (p-value <0.05) is significant at 0.003 level. Conclusion : The molar tooth movement and the osteoclastic count were significantly reduced in BP - Pamidronate administered animals than non-drug recipients. How to cite the article: Venkataramana V, Chidambaram S, Reddy BV, Goud EV, Arafath M, Krishnan S. Impact of Bisphosphonate on Orthodontic tooth movement and olsteoclastic count: An Animal Study. J Int Oral Health 2014;6(2):1-8.

Advances in cytomechanics in orthodontic tooth movement / 医用生物力学

In recent years, great development has been made in cytomechanics in orthodontic tooth movement（OTM）.The essential role of periodontal ligament in OTM has been widely accepted. The in vitro models have become an important way to reveal the biological mechanism in OTM,largely based on periodontal ligament cells(PDLCs), as well as other cells, including bone marrow mesenchymal stem cells, osteoblast, cementoblast and myoblast.The in vitro models have been renovated from the traditional ways stressing the 2D cultured cells by deformation of the bottom,gravity, hydrostatic pressure or centrifugation, to the establishment of various novel models loading mechanical stimulation on cells 3D cultured in bioscaffolds. The molecular expression involved in the osteoblastic differentiation and osteoclastogenesis induction in the bone remodeling cycle has drawn great attention, and will continue to be a focus of study. Furthermore, with the identification of periodontal ligament stem cells(PDLSCs), the cytomechanics involved in OTM and periodontitis, will undoubtedly be a promising new direction.