Effect of Local Subperiosteal Zoledronic Acid Injection on the Survival of Orthodontic Miniscrews

Background: Orthodontic miniscrews are widely used as temporary anchorage devices; however, failure remains a clinical concern. Bisphosphonates may enhance bone stability, but evidence on their local application is limited.

Objective: To evaluate the effect of local subperiosteal zoledronic acid (ZA) injection on miniscrew survival and peri-miniscrew inflammation.

Materials and Methods: This triple-blind, split-mouth randomized controlled trial included 68 patients requiring bilateral maxillary premolar extraction. Miniscrews were placed bilaterally, with one side randomly receiving a 0.5 mL solution of zoledronic acid at 1 mg/mL concentration and the contralateral side saline. Injections were administered weekly for three weeks. Orthodontic force (~250 g) was applied 24 hours after final injection. The primary outcome was miniscrew survival at 6 months. Paired comparisons were analyzed using McNemar test, with odds ratios (ORs) and 95% confidence intervals (CIs).

Study Overview

• Status: Completed
• Conditions: Orthodontic Appliance Complication
• Intervention / Treatment: Drug: Zoledronic Acid; Drug: Normal saline (0.9% sodium chloride)

Detailed Description

Anchorage in orthodontics refers to resistance against unwanted tooth movements during treatment. Numerous methods and devices have been utilized over time to reinforce anchorage. Although effective, these traditional techniques present certain limitations.

Recently, mini-implants, or temporary anchorage devices (TADs), have gained popularity as reliable tools for facilitating controlled tooth movement without relying on patient compliance. Nonetheless, miniscrews can encounter complications including mobility and failure during treatment. Clinically, miniscrew success is generally assessed by absence of inflammation, mobility, or significant pain, along with their capacity to withstand orthodontic forces. A systematic review and meta-analysis estimated that TAD failure occurs in approximately 13.5% of cases, with mandibular placements showing a higher failure rate (16.5%) compared to maxillary ones (11.0%).

Bisphosphonates (BPs) are synthetic compounds analogous to pyrophosphates.They are mainly prescribed to manage excessive bone resorption associated with skeletal disorders, primarily by modulating bone remodeling and repair.

The biological effects of bisphosphonates can be categorized into:

• Tissue level: BPs reduce bone turnover, thereby diminishing both bone resorption and formation.
• Cellular level: Osteoclasts are the primary targets, with bisphosphonates inhibiting their recruitment, suppressing activity, shortening lifespan, and modifying bone mineral properties to slow dissolution independently of cellular processes.

In oral surgery, bisphosphonates have been studied for their influence on implant osseointegration. Clinical trials in humans have reported similar improvements in implant stability and reductions in marginal bone loss. In orthodontics, bisphosphonates have shown promising results by significantly reducing root resorption, maintaining anchorage, and inhibiting osteoclast formation triggered by orthodontic forces, ultimately slowing tooth movement in experimental models. Recent evidence suggests that localized delivery of bisphosphonates is a beneficial adjunct to orthodontic therapy.35 Among bisphosphonates, zoledronic acid (ZA) is recognized as the most potent agent in clinical practice. A single intraoperative dose has shown positive outcomes in multiple bone healing and regeneration models.

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Syria
  • Latakia Governorate
    • Latakia, Latakia Governorate, Syria
      • Latakia university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Mild to moderate skeletal Class II Division 1 malocclusion with full-cusp Class II molar relationship, ANB angle between 4° and 6°, normal maxilla-mandibular plane angle (25° ± 5°), and indication for first premolar extraction to reduce overjet.

Exclusion Criteria:

• Periodontal disease or alveolar bone loss.
• Craniofacial deformities.
• Cleft lip or palate.
• Impacted or missing teeth in the treatment area.
• Systemic diseases or current medication affecting bone metabolism.
• Poor gingival health.
• Smoking or inadequate oral hygiene.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention (Zoledronic Acid); zoledronic acid administered miniscrews	Drug: Zoledronic Acid; Zoledronic acid was prepared at a concentration of 1 mg/mL according to the manufacturer's instructions (ADMAC Pharmaceuticals). A volume of 0.5 mL was injected subperiosteally adjacent to miniscrews on the experimental side. Dose calculation was based on conversion from animal studies using the human equivalent dose (HED) formula.39,40 The calculated HED was 0.0216 mg/kg, corresponding to approximately 1.296 mg for a 60-kg individual. One week after placement, injections were administered weekly for three consecutive sessions.; Other Names: Bisphosphonate
Placebo Comparator: Placebo / Saline Group; saline administered miniscrews	Drug: Normal saline (0.9% sodium chloride); Three local subperiosteal injections of sterile 0.9% saline solution were administered at the orthodontic miniscrew insertion sites, beginning one week after placement and repeated at weekly intervals for three consecutive sessions, serving as an inert control without pharmacological effect.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mobility	Proportion of orthodontic miniscrews with no clinical mobility during follow-up, assessed by manual clinical examination	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peri-miniscrew inflammation	assessed using a 3-point index: (0) healthy; (1) mucositis; (2) peri-implantitis with mobility and failure	6 months

Collaborators and Investigators

• Sponsor: Latakia University
• Investigators: Principal Investigator: Shadi G Moawad, Ph.D, Assistant Professor

Publications and helpful links

General Publications

• Feldmann I, Bondemark L. Orthodontic anchorage: a systematic review. Angle Orthod 2006;76:493-501.
• Ganzer N, Feldmann I, Bondemarkc L. Anchorage reinforcement with miniscrews and molar blocks in adolescents: A randomized controlled trial. Am J Orthod Dentofacial Orthop 2018;154:758-67
• Lee SJ, Ahn SJ, Lee JW, Kim SH, Kim TW. Survival analysis of orthodontic mini-implants. Am J Orthod Dentofacial Orthop. 2010;137:194-9
• Moghaddam S, Mohammadi A, Behroozian A. The effect of sandblasting and acid etching on survival rate of orthodontic miniscrews: a split-mouth randomized controlled trial. Progress in Orthodontics 2021; 22:2.
• Kloehn SJ. Orthodontics-force or persuasion. Angle Orthod 1953; 23:55-65

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Actual): November 2, 2025
• Study Completion (Actual): February 3, 2026

Study Registration Dates

• First Submitted: April 9, 2026
• First Submitted That Met QC Criteria: April 16, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Bisphosphonates; Zoledronic acid; Temporary anchorage devices; Orthodontic miniscrews; Anchorage reinforcement
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Azoles; Imidazoles; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Organophosphorus Compounds; Organophosphonates; Sodium Compounds; Chlorides; Hydrochloric Acid; Zoledronic Acid; Diphosphonates; Saline Solution; Sodium Chloride
• Other Study ID Numbers: LatakiaU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No