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Completed

NCT Number: NCT07546058

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).

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Key information

Age range

17 year–28 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Latakia University

Latakia, Latakia Governorate, Syria

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Zoledronic acid

Drug

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

Normal Saline (0.9% Sodium Chloride)

Drug

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.

Primary outcomes

  1. Mobility

    Time frame: 6 months

    Proportion of orthodontic miniscrews with no clinical mobility during follow-up, assessed by manual clinical examination

Secondary outcomes

  1. Peri-miniscrew inflammation

    Time frame: 6 months

    assessed using a 3-point index: (0) healthy; (1) mucositis; (2) peri-implantitis with mobility and failure

Sponsors and collaborators

Lead sponsor

Latakia University

Other

Registry information

Important dates

Study start
2024
Primary completion
2025
Study completion
2026
First posted
Apr 22, 2026
Registry last updated
Apr 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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