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).

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.

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.