Comparing MOP, Prostaglandin E1, and Calcitriol to Accelerate Orthodontic Tooth Movement (acceleration)

A Comparative Clinical Evaluation of the Mini-Implant Facilitated Micro-Osteoperforation (MOP), Prostaglandin E1 and Calcitriol Injections in Accelerating of Orthodontic Tooth Movement: Randomized Controlled Clinical Trial

This study will compare the effects of MOP (micro-osteoperforation), prostaglandin E1, and calcitriol on the rate of orthodontic tooth movement. The study will evaluate whether these interventions can accelerate tooth movement during orthodontic treatment. The findings may help researchers better understand methods for making orthodontic treatment more efficient while evaluating the effects and safety of the interventions used in the study.

Study Overview

• Status: Recruiting
• Conditions: Accelerated Orthodontic Tooth Movement
• Intervention / Treatment: Procedure: microosteoperforation MOP (surgical); Drug: PGE₁ (pharmacological) • Agent: Prostaglandin E1; Drug: Calcitriol (1,25-(OH)₂D₃) local injection • Agent: Calcitriol (1,25-(OH)₂D₃) Vitamin D3

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ghufran Dhari Awad, MSc. Orthodontics; Phone Number: +9647709644834; Email: ghufrandhari822@gmail.com
• Study Contact Backup: Name: Ali Mohammed Hameed, Ph.D. Orthodontics; Phone Number: +9647709644834; Email: ghufrandharidata@gmail.com

Study Locations

• Iraq
  • Baghdad Governorate
    • Baghdad, Baghdad Governorate, Iraq
      • Recruiting
      • College of Dentistry, University of Baghdad
      • Contact: College of Dentistry, University of Baghdad College of Dentistry, University of Baghdad; Phone Number: +964 770 581 4633; Email: master@codental.uobaghdad.edu.iq
      • Contact: Ghufran Dhari Mfarej, MSc. Orthodontics; Phone Number: +9647709644834; Email: ghufrandhari822@gmail.com
      • Sub-Investigator: Ghufran Mfarej
    • Baghdad, Baghdad Governorate, Iraq, 10001
      • Recruiting
      • College of Dentistry, University of Baghdad
      • Contact: College of Dentistry, University of Baghdad College of Dentistry, University of Baghdad; Phone Number: +964 770 581 4633; Email: master@codental.uobaghdad.edu.iq
      • Contact: Ghufran Mfarej, MSc. Orthodontics; Phone Number: +9647709644834; Email: ghufrandhari822@gmail.com
      • Sub-Investigator: Ghufran Mfarej, MSc. Orthodontics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 25 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient age 18-25.

  • Patient with moderate crowding in mandibular anterior region with Little Irrigularity Index (LII) 4-6 mm.
  • Indicated for fixed orthodontic appliance therapy (non-extraction treatment)
  • Healthy periodontium (probing depths ≤3 mm, gingival and plaque indices6 scores ≤ 1, bleeding on probing ≤ 10%).
  • Presence of all the mandibular permanent teeth, except the third molars.
  • The overbite and overjet should not impede bracket placement on the mandibular anterior teeth.

Exclusion Criteria:

Systemic diseases affecting bone (osteoporosis, endocrine disorders), kidney disease, hyperparathyroidism.

• Medications affecting bone metabolism (bisphosphonates, systemic steroids, Vitamin D3 supplements).
• Known allergy to study agents or local anesthetics.
• History of previous orthodontic intervention
• History of trauma or root resorption in the mandibular anterior teeth

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - MOP (surgical); Arm A - MOP (surgical) patients receiving orthodontic treatment using a straight wire appliance with MBT prescription brackets and a 0.022-inch slot • Anatomical target: labial cortical plate of mandibular anterior segment spanning canine to canine. Procedure: On the bonding day of the fixed appliance, self-drilling mini-implants (1.6 mm in diameter and 6 mm in length) were used to perform the MI-MOPs procedure in MOP (surgical) intervention group. Labial transmucosal MI-MOPs will be performed between the mandibular canine and lateral incisor bilaterally and between the central incisors. Two MI-MOPs at each site were performed, 2 mm and 4 mm below the alveolar bone crest. The perforation depth was decided by adding gingival tissue depth (measured by transgingival probing using Periodontal probe) plus buccal cortical bone depth (using coronal and sagittal sections of CBCT) at the level of planned perforation sites, procedure of MOP will be conducted at Day 1, , two months, 4 months.	Procedure: microosteoperforation MOP (surgical); Micro-osteoperforation is a minimally invasive surgical technique designed to capture the therapeutic advantages of the Regional Acceleratory Phenomenon (RAP). First defined in bone healing, the RAP is a protective physiological mechanism where local tissue tolerance to structural injury triggers a transient, localized burst of tissue remodeling. By creating small, superficial pinhole perforations directly through the cortical plate of the alveolar bone into the spongy marrow spaces-without raising a full-thickness mucoperiosteal flap-MOP induces a highly localized state of controlled surgical trauma (Bolat, 2019; Farag et al., 2021). This injury provokes an immediate surge in pro-inflammatory cytokines (IL-1$\beta$, TNF-$\alpha$, and IL-6), leading to an elevated RANKL/OPG ratio.
Experimental: Arm B - PGE₁ (pharmacological); patients receiving orthodontic treatment using straight wire appliance with MBT prescription brackets and a 0.022-inch slot size (Pinnacle®, Ortho Technology, USA).; Dose & sites (mandibular anterior): 60 µg per visit, 10 µg (0.02mL) per site injected in to PDL at 6 sites across the mandibular anterior segment (one injection for each single tooth).; Timing: single dose at Day 1; repeat every two weeks for 4 months. PGE1 injection will be preceded by Mental nerve block bilaterally using local anesthetic solution . The calculation of Prostaglandin E₁ dose that will be used in the current study occur according to previous clinical trials. However, in our study the target site are six mandibular anterior teeth, by multiplying dose per tooth by number of teeth, so the recommended dose will be 60 µg per visit distributed as 10 µg (0.02mL) per site. Furthermore, the normal physiological serum level for Prostaglandin E₁ 1.2-1.8 µg/mL taken in consideration	Drug: PGE₁ (pharmacological) • Agent: Prostaglandin E1; Prostaglandin analogs are synthetic compounds that mimic the effects of naturally occurring prostaglandins and are used for a wide range of clinical indications. They are used across multiple specialties, including ophthalmology, obstetrics, urology, gastroenterology, cardiology, and pulmonology.
Experimental: Arm C - Calcitriol (1,25-(OH)₂D₃) local injection; patients receiving orthodontic treatment using straight wire appliance with MBT prescription brackets and a 0.022-inch slot size (Pinnacle®); Dose & sites: 60 pg per visit, 10 pg per site injected in to PDL at 6 sites across the mandibular anterior segment (one injection for each single tooth); Timing: single dose on Day 1; repeats every two weeks for 4 months. Calcitriol injection is preceded by Mental nerve block bilaterally using local anesthetic solution to relieve pain usually accompanied with injection techniques. In the current study, Dimethylsulfoxide (0.2 mL) (DMSO, Bisolve B.V., Netherlands) will be used for dilution with dilution factor (1:20000000) and worked as a vehicle which used in previous clinical trials The calculation of Calcitriol dose that will be used in the current study occur according to previous clinical trials and normal physiological serum level for Calcitriol is 25-66 pg/mL . So, recommended dose will be 60 pg per visit distributed as 10 pg per site	Drug: Calcitriol (1,25-(OH)₂D₃) local injection • Agent: Calcitriol (1,25-(OH)₂D₃) Vitamin D3; It is a biologically active form of vitamin D and plays an important role in calcium homeostasis (Reddy SR et al., 2015). A decrease in the serum calcium level stimulates secretion of PTH, which in turn increases excretion of PO4 3-, reabsorption of calcium from the kidneys, and hydroxylation of 25, hydroxycholecaliferol to 1, 25, DHCC.
No Intervention: Arm D -Control; patients receiving no intervention(surgical or pharmacological ) just only orthodontic treatment using a straight wire appliance with MBT prescription brackets and a 0.022-inch slot size (Pinnacle®, Ortho Technology, USA). participants receive the same standardized orthodontic mechanics, fixed orthodontic appliances (stainless steel MBT .022) were used in the current study with archwires sequence 0.014 NiTi 0.018 NiTi 0.017*0.025 NiTi 0.019*0.025 NiTi 0.019*0.025 SS (Ortho Technology, USA) (Al-Attar et al.,2022; Noori et al., 2025) Archwire will be replaced when expected improvement was achieved and next archwire could be inserted with minimal deflection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
orthodontic tooth movement	To compare the difference in the amount of tooth movement of the mandibular anterior segment in term of Little Irrigularity Index (LII) after 6 months from the start of treatment among four arms: MOP, local PGE₁ injection, local calcitriol injection, and control.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
biomarkers	To compare the levels of Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL), Osteoprotegerin (OPG), Interleukin-1beta (IL-1β) biomarkers in gingival crevicular fluid (GCF)	at baseline, 24 hours, 1 week and 4 weeks from the start of treatment
orthodontically-induced inflammatory root resorption (OIIRR)	To compare the amount of orthodontically-induced inflammatory root resorption (OIIRR) in the apical region of mandibular anterior teeth	before starting orthodontic treatment and after finishing leveling &alignment phase
pain perception	To compare the amount of pain perception during the 1st week after each archwire placement among the two pharmacological agents, microosteoperforation and control groups.	during the 1st week & after each archwire placement

Collaborators and Investigators

• Sponsor: Ghufran Dhari Awad
• Investigators: Study Director: Ghufran Mfarej, college of dentistry /university of Baghdad

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2026
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: September 20, 2026
• First Submitted That Met QC Criteria: September 20, 2026
• First Posted (Actual): September 25, 2026

Study Record Updates

• Last Update Posted (Actual): September 25, 2026
• Last Update Submitted That Met QC Criteria: September 20, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Fatty Acids; Lipids; Biological Factors; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Autacoids; Inflammation Mediators; Cholestenes; Cholestanes; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Hydroxycholecalciferols; Dihydroxycholecalciferols; Cholecalciferol; Calcitriol; Surgical Procedures, Operative; Prostaglandins E
• Other Study ID Numbers: 1198426

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

LII, Biomarkers, root resorption, pain perception

• IPD Sharing Supporting Information Type: SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No