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

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          Abstract

          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)

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          Most cited references53

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          The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials

          Flaws in the design, conduct, analysis, and reporting of randomised trials can cause the effect of an intervention to be underestimated or overestimated. The Cochrane Collaboration’s tool for assessing risk of bias aims to make the process clearer and more accurate
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            Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

            Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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              Osteoclast differentiation and activation.

              Osteoclasts are specialized cells derived from the monocyte/macrophage haematopoietic lineage that develop and adhere to bone matrix, then secrete acid and lytic enzymes that degrade it in a specialized, extracellular compartment. Discovery of the RANK signalling pathway in the osteoclast has provided insight into the mechanisms of osteoclastogenesis and activation of bone resorption, and how hormonal signals impact bone structure and mass. Further study of this pathway is providing the molecular basis for developing therapeutics to treat osteoporosis and other diseases of bone loss.
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                Author and article information

                Contributors
                sabuarqub@uchc.edu
                Gandhi@uchc.edu
                gauthier@uchc.edu
                maramsa@bu.edu
                kuo@uchc.edu
                mu@uchc.edu
                edutra@uchc.edu
                Uribe@uchc.edu
                Journal
                Prog Orthod
                Prog Orthod
                Progress in Orthodontics
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1723-7785
                2196-1042
                1 February 2021
                1 February 2021
                2021
                : 22
                : 5
                Affiliations
                [1 ]GRID grid.208078.5, ISNI 0000000419370394, Division of Orthodontics, , University of Connecticut Health, ; 263 Farmington Ave, Farmington, CT 06032 USA
                [2 ]GRID grid.208078.5, ISNI 0000000419370394, L.M. Stowe Library, , University of Connecticut Health, ; Farmington, CT USA
                [3 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Division of Orthodontics, , University of Boston, ; Boston, MA USA
                [4 ]GRID grid.208078.5, ISNI 0000000419370394, Connecticut Convergence Institute for Translation in Regenerative Engineering, , University of Connecticut Health, ; Farmington, CT USA
                Author information
                http://orcid.org/0000-0003-4592-0954
                Article
                349
                10.1186/s40510-021-00349-5
                7851211
                33523325
                1c51e330-eae3-4a5d-8abb-30d92e7f4706
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 20 November 2020
                : 11 January 2021
                Categories
                Review
                Custom metadata
                © The Author(s) 2021

                orthodontic tooth movement,acceleration,biological agents,prostaglandins,vitamin d,platelet-rich plasma,vitamin c,relaxin,human trials

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