Characterizing orthodontic tooth movement in real time using dental monitoring scans: A pilot study.

OBJECTIVES: This pilot study aimed to quantify the magnitude and type of tooth movement occurring in short time intervals within the regular monthly orthodontic visits for patients with fixed appliances and undergoing maxillary canine retraction. Additionally, this pilot study aimed to provide a descriptive evaluation for the accuracy and reliability of the Dental Monitoring (DM)-captured scans to those of an iTero digital scans in an extraction space closure model. SETTINGS AND SAMPLE POPULATION: 3D intraoral photographic scans (DM) for 12 patients with maxillary first premolar extractions in a single-centre academic institution. MATERIALS AND METHODS: Twelve patients treated with fixed appliances and undergoing space closure for maxillary premolar extraction(s) were included. Nickel-titanium (200 g) closing coil springs were used for canine retraction. At initiation of space closure (T1), iTero scans were acquired, and patients were instructed to take DM scans every 4-5 days until their next visit in 4-5 weeks (T2). At T2, a final iTero scan in addition to a DM scan was taken. The number of patients who did the scans regularly as instructed declined as time elapsed. Stereolithography (STL) files generated from the DM scans were superimposed with the STL files from the iTero scans using GOM Inspect software to determine the accuracy of the DM 3D models. To assess rate, type and direction of tooth movement, each of the 3D image STL files generated from the DM scans, taken every 4-5 days by each patient, was superimposed on the previously captured scan. The rate of tooth movement for the maxillary molars and canines was calculated in the 3 planes of space (X, Y, Z) at each time point, until the end of the experiment. RESULTS: Preliminary results indicated that the maxillary canines appeared to be displaced the greatest amount in the first 4-5 days with initial distolateral movement. As time elapsed, the rate of tooth movement decreased, and the tooth started moving distolingually. CONCLUSIONS: Dental monitoring software provides a high-tech platform to monitor tooth movement in a 'real-time' approach. Accuracy of the photographic scans in relationship to the intraoral scans appears promising. There seems to be some evidence that the greatest amount of movement occurs initially in the first few days after activation, dropping thereafter to become a slower constant rate of tooth movement.

Assessment of the occlusal outcomes in patients treated with orthognathic surgery and clear aligners.

OBJECTIVE: This retrospective two-centre study aimed to evaluate the occlusal outcomes in patients undergoing orthognathic surgery with clear aligners. METHODS: A retrospective chart review and occlusal outcomes for 15 patients (10 females and five males) with different types of dentofacial deformities in the anteroposterior, vertical and transverse dimensions, who underwent orthognathic surgery in conjunction with clear aligners were evaluated. Weighed Peer Assessment Rating (PAR) index scores of the pre-treatment and post-treatment digital models were used to assess initial complexity, final occlusal outcomes and degree of improvement with surgery and clear aligners. RESULTS: The mean post-treatment PAR score was 3.5 ± 2.54, which was a statistically significant improvement from the pre-treatment PAR score of 27.63 ± 12.09, an 87% improvement was achieved. All subcategories of the PAR index showed statistically significant improvement except for midline assessment component. CONCLUSIONS: Occlusal outcomes with aligners showed great improvement as indicated with the PAR index scores. Orthognathic surgical cases can be treated efficiently with aligners and future studies should compare occlusal outcomes between orthognathic surgical patients treated with clear aligners and those treated with fixed appliances.

Survival and failure rate of lower lingual bonded retainers: A retrospective cohort evaluation.

OBJECTIVE: The objectives of the study were to evaluate the survival rates for lower lingual retainers (LLRs) and to establish a correlation between patients' treatment-related factors (age, sex, malocclusion, appliance used for treatment, teeth bonded, retention protocols) to the survival of LLRs. MATERIALS AND METHODS: A total of 765 subjects [474 females and 291 males: mean age = 24.29 ± 10.67 years] between 2013 and 2022 were included. A customized data collection form was utilized to gather the data from the electronic health record (EHR) of subjects. Patient-related factors, crowding or spacing, deep bite or open bite and duration of treatment were extracted from patients' files. Kaplan-Meier estimator was used for the survival function, whereas Cox proportional hazards regression models were used to associate risk factors with retainer survival. RESULTS: 328 (42.9%) subjects had their LLRs failed, and the survival period was on average 17.37 ± 22.85 months. On the other hand, the follow-up period for the retainers that did not fail was on average 47.19 ± 23.66 months. 192 (28.3%) subjects had segment failure (retainer detached from 3 teeth or less), while 51 (7.5%) subjects had failures in more than 3 teeth (complete). None of the evaluated clinical variables were significantly associated with LLRs failure except for the bite category (P = .013) and the appliance used for treatment (P < .001). CONCLUSION: Success rate for LLRs was 57.1% over 47.19 months, failure rate was 42.9% over 17.37 months. The presence of deep bite and treatment with aligners were significantly associated with increased failure rate.

The effectiveness of adjuncts or alternatives to the use of orthodontic retainers in preserving posttreatment outcomes: A systematic review.

INTRODUCTION: The objective of this study was to systematically evaluate the efficacy of adjuncts or alternatives to mechanical retention in preserving postorthodontic treatment outcomes. METHODS: Electronic databases, unpublished literature, and ongoing trials were searched until July 22, 2022 (PROSPERO CRD42021291165). Randomized and nonrandomized controlled trials investigating the efficacy of adjuncts and alternatives to conventional orthodontic retainers were included. Stability, periodontal effects, cost-effectiveness, and patient-reported outcomes were to be evaluated. The Cochrane Risk of Bias Tool and Risk of Bias In Nonrandomized Studies of Interventions (ROBINS-I) were used for risk of bias assessment. The certainty of the evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation system. Exploratory sensitivity analysis was undertaken to calculate the weighted treatment effects of the intervention. RESULTS: A total of 5128 records were screened. Seven trials fulfilled the inclusion criteria, of which 5 were randomized controlled trials. Five trials were judged to be at high risk of bias, with 2 studies of unclear risk of bias. Heterogeneity between the limited number of included studies precluded the conduct of meta-analysis. Circumferential supracrestal fibrotomy resulted in less increase in the mandibular Little's Irregularity Index (mean difference, -2.30 mm; 95% confidence interval, -2.86 to -1.74). The overall level of evidence was of very low quality. CONCLUSIONS: Adjuncts and alternatives to mechanical retention have promise, but based on the existing evidence, the reliance on mechanical retention cannot be reduced. There is weak evidence supporting circumferential supracrestal fibrotomy to improve stability outcomes. Further high-quality prospective research focusing on the predictability and acceptability of these approaches is needed.

Insight on the influence of technology-enhanced learning in orthodontics' education: A systematic review.

OBJECTIVES: Technology-enhanced learning (TEL) provides a pliable and current way to present orthodontic curriculum material to students. This review aimed to assess the effectiveness of TEL compared with traditional learning methods in the field of orthodontics. MATERIALS AND METHODS: The search comprised randomised controlled trials (RCTs) related to orthodontics' interactive learning from the following databases: PubMed, Scopus, CENTRAL, Psyclnfo, ERIC, Web of Science, Dissertations and Theses Global. Two authors performed the screening, data extraction and assessed risk of bias using the Cochrane tool (Rob 2) blindly and in duplicate. Kirkpatrick's 4-level evaluation model was used to evaluate educational outcomes. RESULTS: A total of 3131 records were identified of which 11 RCT were included. On level 1 (Reaction), students had a positive attitude towards TEL. On level 2 (Learning), included studies did not report any significant knowledge improvement when TEL was compared with traditional learning strategies. One study assessed level 3 (Behaviour), where students felt that flipped classroom learning created feelings of greater confidence. On level 4 (Results), most studies suggested that TEL tools are as equally effective in imparting information as traditional tools and recommended that both methods should be considered in teaching students. CONCLUSION: Technology-enhanced learning techniques might have the potential to enhance educational outcomes in orthodontic education and students seem to enjoy the implementation of technology in the learning process. These educational tools should be used as an adjunct to the traditional didactic classroom, and not as a replacement, due to the challenges encountered with their application.

Variability associated with mandibular ramus area thickness and depth in subjects with different growth patterns, gender, and growth status.

INTRODUCTION: The purpose of this study was to quantitatively evaluate the ramus bone parameters (ramus thickness and ramus depth) for miniscrew placement. An additional aim was to compare and contrast the ramus bone parameters in growing and nongrowing male and female subjects with hyperdivergent, normodivergent, hypodivergent facial types. METHODS: Cone-beam computed tomography scans of 690 subjects were evaluated. They were classified in terms of growth status, gender, and facial type. Ramus thickness was measured as the distance from the outer (buccal) to the inner (lingual) aspects of the mandibular ramus. Ramus depth was measured as the distance from the anterior border of the ramus to the inferior alveolar nerve canal. The measurements for ramus thickness and ramus depth were performed at 3 different levels bilaterally: (1) occlusal plane (OP), (2) 5 mm above the occlusal plane (5OP), and (3) 10 mm above the occlusal plane (10OP). RESULTS: Males showed a significantly higher ramus thickness than females (P <0.05). Ramus thickness decreased significantly (P <0.05) as we moved superior from the level of OP to 5OP and 10OP in all 3 facial types in both females (growing and nongrowing) and males (growing and nongrowing). Growing females and growing males had significantly higher ramus thickness than nongrowing females and nongrowing males, respectively. Ramus depth increased as we moved higher from the OP to 10OP. Hyperdivergent facial type showed a significantly reduced ramus depth compared with hypodivergent and normodivergent facial type in growing and nongrowing males and females at all 3 locations, namely OP, 5OP, and 10OP (P <0.05). CONCLUSIONS: Because of adequate ramus depth and ramus thickness, 5OP was considered the optimal insertion site for the placement of miniscrews. Patients with a hyperdivergent facial type showed significantly reduced ramus depth than hypodivergent and normodivergent facial types. Ramus thickness in males was significantly higher than in females in all facial types.

Long-term effects of conventional and miniscrew-assisted rapid palatal expansion on root resorption.

INTRODUCTION: The purpose of this study was to use cone-beam computed tomography to compare immediate and long-term effects of conventional and miniscrew-assisted rapid palatal expansion (MARPE) appliances on root resorption in 2 treatment groups and a control group. METHODS: One hundred eighty cone-beam computed tomography images of 60 patients at 3 time points were assessed: initial, postexpansion, and debond. The patients were divided into 3 groups: control (n = 19), rapid palatal expansion (RPE) appliance (n = 21), and MARPE (n = 20). The period of initial to debond varied for the 3 groups: 2 years, 7 months for controls; 2 years, 9 months for RPE; and 2 years, 8 months for MARPE. The length of mesiobuccal, distobuccal, and palatal root of the maxillary first molar (1M); the buccal root of maxillary first premolar; and second premolar were measured. The inclination of the 1M, intercuspal width (ICW), interroot width (IRW), ICW/IRW ratio, maxillary skeletal width were measured in all 3 groups at different time points. RESULTS: Immediately after expansion, RPE and MARPE groups showed a significant increase in the molar inclination, ICW, ICW/IRW ratio, and maxillary skeletal width compared with controls at postexpansion. However, the long-term comparison did not show any significant difference for root resorption and expansion parameters between the 3 groups, except the ICW/IRW ratio, which was higher in MARPE than controls at debond. A significant negative association was observed between the length of the mesiobuccal root of 1M and molar inclination (ß = -0.025; 95% confidence interval, -0.050 to 0.0008; P <0.05). The expansion of ICW and IRW did not show a significant association with root resorption. CONCLUSIONS: The long-term outcomes showed no difference in the amount of root resorption between the RPE, MARPE, and control groups. Molar inclination showed a significant negative association with the length of the mesiobuccal root of the 1M.

Association between initial complexity, frequency of refinements, treatment duration, and outcome in Invisalign orthodontic treatment.

INTRODUCTION: This study explored possible associations between treatment duration, initial complexity, outcomes in Invisalign therapy, and the number of refinements. METHODS: Three-dimensional models (initial, final, and refinements) of 355 Invisalign patients (114 males and 241 females; 33.8 ± 17.1 years) were analyzed using the Peer Assessment Rating (PAR) index questionnaire tool in the Ortho Analyzer software (version 2.0; 3Shape, Copenhagen, Denmark) to calculate the weighted total and individual PAR index scores for each component of the PAR index. Data related to demographics, treatment duration, and the number of refinements were collected. RESULTS: Treatment duration increased as the number of refinements increased. Percent of improvement was higher in PAR ≥22 group than PAR <22 with an increase in the number of refinements: 83.3% vs 73.8% for 2 refinements; 94.7% vs 91.2% for 3 refinements; and 100% vs 85.7% for ≥4 refinements. Those who achieved great improvement or improvement and those who did not were significantly different in treatment duration (P <0.001 and P = 0.027), number of refinements (≥3 refinements; P <0.001), initial occlusal severity (PAR ≥22; P <0.01 and P = 0.031). Most subjects achieved improvement after the first refinement (64.5% for PAR <22 and 78.5% for PAR ≥22). Few had ≥4 refinements, and if they did, none achieved improvement with additional refinements. CONCLUSIONS: Initial complexity for an Invisalign case is associated with treatment duration, achieved outcomes, and the number of refinements. Treatment duration increased with an increased number of refinements. Great improvement or improvement for the first time dropped to 0 if additional refinements were carried out after 3. Therefore, performing additional refinements does not necessarily mean better occlusal outcomes.

The biological sex lens on early orthopaedic treatment duration and outcomes in Class III orthodontic patients: a systematic review.

BACKGROUND: Treatment outcomes for Class III orthopaedic treatment are highly unpredictable and dependent on the timing of interception, age, and biological sex. OBJECTIVE: This systematic review aimed to assess the effects of sex dimorphism on outcomes and duration of orthopaedic treatment for Class III malocclusion in young children. SEARCH METHODS: Unrestricted search in six electronic databases until May 2021 was conducted. Supplemented by search in resources for published, unpublished literature, and ongoing trials. SELECTION CRITERIA: Randomized and non-randomized controlled trials reporting the use of Class III growth modification appliances, with baseline and outcome data for both sexes, were included. DATA COLLECTION AND ANALYSIS: Study selection and data extraction were performed blindly and in duplicate by two reviewers. ROBINS-I, Cochrane Risk of Bias, and GRADE tools were used for certainty assessment. RESULTS: A total of 2429 records were screened. Four trials fulfilled the inclusion criteria, one was a randomized clinical trial (RCT) comparing facemask and facemask with mini-screw. Two clinical trials evaluated the effects of facemask appliance, one had a control group, another was prospective non-controlled. One compared the effects of the maxillary protraction bow appliance to a no treatment control. Two of the clinical trials were appraised as low and one was appraised as high risk of bias. The overall certainty of the available evidence was assessed as moderate. There was significant clinical heterogeneity in terms of methodology, type of intervention, and the measured outcomes, precluding a meta-analysis. CONCLUSIONS: Minimal variations in sagittal, vertical, and dentoalveolar post-treatment cephalometric changes were reported between sexes. The available evidence is unclear to support these variations. Long-term-powered RCTs assessing cephalometric outcomes between sexes until the end of growth spurt and without pooling are not available, therefore, much needed. REGISTRATION: PROSPERO database number CRD42020185797.

Biomechanics of conventional and miniscrew-assisted rapid palatal expansion.

Posterior Crossbite is a common condition resulting because of transverse maxillary deficiency. The growth of the craniofacial complex finishes first in the transverse dimension, followed by sagittal and vertical dimensions. Conventional rapid palatal expansion (RPE) appliances are commonly used to correct transverse maxillary deficiency. Although RPE is efficient in correcting posterior crossbite, it results in dental side effects such as buccal tipping of maxillary molars, root resorption, bone dehiscence, and relapse. Mini-implant-assisted RPE has been introduced to increase the skeletal effects of expansion especially in patients with increased maturation and greater interdigitation of midpalatal suture. This article will review the biomechanics of RPE and mini-implant-assisted RPE. Additionally, the different designs of MARPE and the long-term clinical effects of expansion appliances will also be discussed in detail.

Orthodontic Localization of Impacted Canines: Review of the Cutting-edge Evidence in Diagnosis and Treatment Planning Based on 3D CBCT Images.

A thorough clinical and radiographical assessment of an impacted maxillary canine's location forms the basis for proper diagnosis and successful treatment outcomes. Implementing a correct biomechanical approach for directing force application primarily relies on its precise localization. Poor biomechanical planning can resorb the roots of adjacent teeth and result in poor periodontal outcomes of the canine that has been disimpacted. Furthermore, treatment success and time strongly rely on an accurate assessment of the severity of impaction, which depends on its 3D spatial location. The evolution of cone-beam computed tomography (CBCT) radiographs provides more detailed information regarding the location of the impacted canines. In addition, the literature has shown that CBCT imaging has enhanced the quality of diagnosis and treatment planning by obtaining a more precise localization of impacted canines. This review article highlights current evidence regarding comprehensive evaluation of three-dimensional orientations of impacted canines on CBCT images for precise diagnosis and treatment planning.

An analysis of dental articles in predatory journals and associated online engagement.

OBJECTIVE: We aimed to assess the extent of social media sharing of presumed predatory (PP) dental journals and to compare level of engagement, type of accounts and characteristics of the articles published in presumed legitimate (PL) and PP journals. METHODS: Six hashtags were searched across three social media platforms (Instagram, Facebook and Twitter). Data extraction was performed and journals were classified into PP or PL in a multistep approach using MEDLINE, Beall's list and Directory of Open Access Journals (DOAJ). A checklist was created and used for studies not found in the aforementioned recognized databases. RESULTS: A total of 1742 posts were identified, with the majority (94%) found on Instagram. Of the identified journals, 15.6% were PP. Over one-third of articles from PP journals (35.42%) were indexed on PubMed. The majority of presumed legitimate publications were published in dental specialty only journals (56.44%), compared to 24% in the PP group. The majority of accounts were those of healthcare professionals with most publications related to prosthodontics and implantology (26.3%) and restorative and esthetic dentistry (14.4%), in PL and PP groups, respectively. Similar median number of followers/friends and comments were found among the PL and PP groups. CONCLUSION: Our findings highlight that presumed predatory publications have comparable reach to PL journals on social media risking the sharing of unreliable and misleading information. CLINICAL SIGNIFICANCE: Researchers, students and social media users should be capable of identifying presumed predatory dental publications. Means of moderating the influence of these publications should be explored.

Biomechanics of clear aligners: hidden truths & first principles.

Over the past two decades clear aligner-based treatment has received remarkableattention from the orthodontic profession and more so from general practitioners.Different companies have emerged using vigorous advertisement to promote theirproducts mainly to patients and clinicians through social media. A variety of concepts,methods, and adjuncts have been introduced to enhance the efficacy andeffectiveness of clear aligners. However, the accuracy of tooth movement (vspredicted) with aligners still hovers around 50%. Fixed appliances fare much better onaccuracy and predictability of treatment. Why is there a discrepancy betweenexpected and actual outcomes? This paper utilizes 'first principles' and the existingevidence to unravel some of the key drawbacks of aligner-based therapy. Severalshortcomings in the biomechanical properties of aligner material (thermoplastics) thataffect clinical performance are discussed. Based on the first principles of alignerbiomechanics, this paper provides clinical insights for improving predictability and effectiveness of aligner therapy.

Evaluation of interproximal reduction in individual teeth, and full arch assessment in clear aligner therapy: digital planning versus 3D model analysis after reduction.

AIM: To evaluate the correspondence between the interproximal reduction (IPR) performed clinically and that programmed in ClinCheck® and further assess which teeth showed an amount of implemented IPR (I-IPR) that corresponds with that programmed in ClinCheck®. MATERIALS AND METHODS: Pre- (T0) and post-treatment (T1) ClinCheck® digital models for 75 subjects (30 males and 45 females), mean age (38 ± 15) years, were included. To calculate the amount of I-IPR, Ortho Analyzer software (3Shape, Copenhagen, Denmark) was used to measure the mesiodistal widths for the maxillary and mandibular teeth from second premolar to the contralateral second premolar on the initial (T0) and final (T1) STL models. I- IPR performed by tooth was obtained by comparing the mesiodistal width of each tooth at T0 and T1. The amount of programmed IPR (P-IPR) in ClinCheck® was compared to that implemented clinically using the following formula: IPR difference = (P-IPR) - (I-IPR). RESULTS: Statistically significant differences were observed between the average value of digitally programmed and implemented IPR per tooth for both the maxillary (p < .0001) and mandibular (p < .0001) teeth. The mean P-IPR for the maxillary teeth was 0.28 ± 0.16 mm versus the mean I-IPR of 0.15 ± 0.15 mm. In the mandibular arch, the mean P-IPR was 0.31 ± 0.17 mm, while the I-IPR was 0.17 ± 0.16 mm. The mean I-IPR was consistently lower than the mean P-IPR regardless of teeth and sites (p < 0.0001). The difference between the P-IPR compared to the I-IPR was larger for mandibular anterior teeth than for maxillary anterior teeth (p = 0.0302) and larger for maxillary posterior teeth than mandibular posterior teeth (p = 0.0059). CONCLUSION: The amount of implemented-IPR in clear aligner therapy is less than that digitally programmed for most teeth. Regardless of the regions, I-IPR was consistently lower than that programmed. Mandibular anterior teeth and maxillary posterior teeth showed greater discrepancy between P-IPR and I-IPR than the maxillary anterior and mandibular posteriors. Further prospective studies are needed to determine the factors affecting the precision of IPR and the clinical implications of a significantly reduced I-IPR on treatment outcomes.

Survival estimates and risk factors for failure of palatal and buccal mini-implants.

OBJECTIVES: The primary objective was to compare the success and survival rates of palatal and buccal mini-implants for different locations and treatment requirements. The secondary objective was to evaluate risk factors influencing the survival of mini-implants. MATERIALS AND METHODS: In this retrospective cohort, records of 127 orthodontic patients with 257 mini-implants were included after imposing inclusion/exclusion criteria. Along with the implant failure data, factors such as age, sex, transverse location, anteroposterior location, and purpose of mini-implants were recorded. Kaplan-Meier survival analysis was used to draw the curves and a Nathan Mantel-David Cox test to compare variables. RESULTS: The failure rate of palatal mini-implants was 8.5%, whereas the failure rate for buccal shelf mini-implants was 68.7% (P < .0001). A significant difference was that the survival rates of palatal mini-implants were dependent on the purpose of the mini-implants and, for the buccal mini-implants, they were dependent on the skeletal malocclusion and location type of mini-implants (P < .05). CONCLUSIONS: The overall survival rate of palatal mini-implants was high, at 91.5%. Of the buccal mini-implants, inter-radicular mini-implants had the highest survival rate for 12 (75.5%) and 24 (71.9%) months, while buccal shelf mini-implants had the lowest success and survival rates for 12 (31.3%) and 24 (20.8%) months. Class III malocclusion had the lowest survival rate for the buccal mini-implants (65.3% and 54.2%) for 12 and 24 months.

Patients' perceptions of orthodontic treatment experiences during COVID-19: a cross-sectional study.

BACKGROUND: COVID-19 has impacted the care of patients undergoing orthodontic treatment. We aimed to provide an overall view of patients' perspectives, concerns, and expectations towards their treatment throughout the clinic lockdown during the pandemic; and to assess patients' levels of mental distress and its association with their confidence in resuming care. METHODS: An anonymous, validated, in-person paper questionnaire was distributed to adult orthodontic patients' post-lockdown at an academic institution. The survey focused on the clinical aspects and patients' perspectives regarding orthodontic treatment during the pandemic. The Kessler Mental Distress Scale (K10) was used to evaluate their psychological status. Survey responses were descriptively summarized and confidence in resuming care was compared between normal patients and patients with mental distress using Mann-Whitney tests. RESULTS: One hundred fifty-four patients were surveyed from July to October 2020. Mean age of the participants was 29.30 (SD = 12.01) years and 62% were females. Emergencies during the closure (21%, 32/154) involved primarily irritation with protruding wires. Patients were neutral regarding tele-dentistry and preferred their current fixed appliances over clear aligners. Upon resuming care, 80.51% were extremely pleased with the restrictive protocols and with high level of confidence in resuming treatment. The average level of anxiety was low, and a modest association was found between mental distress and reduced confidence in resuming treatment. CONCLUSIONS: Few numbers of minor emergencies occurred during the clinic closure. Despite the rising interest in tele-dentistry, patients were neutral on considering this option to monitor treatment and were content with fixed appliances. Patients had high confidence levels to resume their care based on the protocols established upon reopening. The association of mental distress and confidence in resuming care is suggestive and needs further investigation.

The effect of the local administration of biological substances on the rate of orthodontic tooth movement: a systematic review of human studies.

BACKGROUND: The influence of different biological agents on the rate of orthodontic tooth movement (OTM) has been extensively reviewed in animal studies with conflicting results. These findings cannot be extrapolated from animals to humans. Therefore, we aimed to systematically investigate the most up-to-date available evidence of human studies regarding the effect of the administration of different biological substances on the rate of orthodontic tooth movement. METHODS: A total of 8 databases were searched until the 16th of June 2020 without restrictions. Controlled randomized and non-randomized human clinical studies assessing the effect of biological substances on the rate of OTM were included. ROBINS-I and the Cochrane Risk of Bias tools were used. Reporting of this review was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 11 studies (6 randomized clinical trials and 5 prospective clinical trials) were identified for inclusion. Local injections of prostaglandin E1 and vitamin C exerted a positive influence on the rate of OTM; vitamin D showed variable effects. The use of platelet-rich plasma and its derivatives showed inconsistent results, while the local use of human relaxin hormone showed no significant effects on the rate of OTM. LIMITATIONS: The limited and variable observation periods after the administration of the biological substances, the high and medium risk of bias assessment for some included studies, the variable concentrations of the assessed biological agents, the different experimental designs and teeth evaluated, and the variety of measurement tools have hampered the quantitative assessment of the results as originally planned. CONCLUSIONS AND IMPLICATIONS: Despite the methodological limitations of the included studies, this systematic review provides an important overview of the effects of a variety of biological agents on the rate of tooth movement and elucidates the deficiencies in the clinical studies that have been conducted so far to evaluate the effectiveness of these agents in humans, providing some guidelines for future robust research. TRIAL REGISTRATION: PROSPERO ( CRD42020168481 , www.crd.york.ac.uk/prospero ).