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

Prog Orthod. 2021 Feb 1;22(1):5. doi: 10.1186/s40510-021-00349-5.


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 , ).

Keywords: Acceleration; Biological agents; Human trials; Orthodontic tooth movement; Platelet-rich plasma; Prostaglandins; Relaxin; Vitamin C; Vitamin D.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Biological Factors
  • Humans
  • Prospective Studies
  • Research Design
  • Tooth Movement Techniques*
  • Tooth*


  • Biological Factors