Oxidative Stress and Antioxidant Responses During Rapid Maxillary Expansion: A Controlled Clinical Study

Rapid maxillary expansion is an orthopedic treatment used to correct transverse maxillary deficiency in growing patients. Mechanical forces generated during expansion may induce local biological responses, including changes in oxidative stress and antioxidant defense mechanisms.

This prospective, non-randomized, controlled pilot study evaluated changes in oxidative and antioxidant biomarkers in gingival crevicular fluid during rapid maxillary expansion and the early retention period. Twenty-eight participants aged 10 to 13 years were included: 14 patients undergoing rapid maxillary expansion and 14 age- and sex-matched untreated controls.

Gingival crevicular fluid samples and periodontal measurements were collected at six corresponding time points. Malondialdehyde, reduced glutathione, glutathione peroxidase, and vitamin C were measured. The study aimed to characterize local biochemical changes associated with the treatment period and to compare their longitudinal patterns with those observed in untreated controls.

Study Overview

• Status: Completed
• Conditions: Transverse Maxillary Deficiency; Oxidative Stress
• Intervention / Treatment: Procedure: Expansion group

Detailed Description

Rapid maxillary expansion is widely used to correct transverse maxillary deficiency in growing patients. Although its skeletal and dentoalveolar effects are well established, the local biochemical responses associated with active expansion and early retention remain incompletely characterized. Mechanical loading may increase the production of reactive oxygen species and alter antioxidant defense mechanisms within periodontal tissues.

The purpose of this study was to evaluate longitudinal changes in oxidative stress and antioxidant biomarkers measured in gingival crevicular fluid during rapid maxillary expansion and to compare these changes with those observed in an untreated control group.

Twenty-eight consecutively recruited orthodontic patients aged 10 to 13 years were included. Fourteen patients with a clinical indication for rapid maxillary expansion formed the intervention group. Fourteen untreated participants, matched by age and sex, formed the control group. Treatment allocation was not randomized because the decision to perform rapid maxillary expansion was based on clinical need.

Participants in the intervention group were treated with a modified Hyrax rapid maxillary expander. The appliance was initially maintained without activation and was subsequently activated twice daily, corresponding to approximately 0.5 mm of expansion per day, until the planned expansion was achieved. After active expansion, the screw was stabilized with composite resin and the appliance was maintained as a retention device.

Clinical periodontal assessments and gingival crevicular fluid sampling were performed at six time points: baseline; 24 hours after appliance placement; 7 days after appliance placement during the passive phase; after 7 days of active expansion; after 14 days of active expansion; and after 3 months of retention. Control participants underwent the same assessment schedule without orthodontic intervention.

Gingival crevicular fluid was analyzed for malondialdehyde, reduced glutathione, glutathione peroxidase activity, and vitamin C. Biomarker values were normalized to total protein concentration. Periodontal measurements included gingival index, plaque index, probing depth, and keratinized tissue percentage.

The study was exploratory and no formal prospective sample size calculation was performed. The findings were intended to characterize local biochemical changes in gingival crevicular fluid and were not designed to provide direct evidence of skeletal or midpalatal suture remodeling.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Turkey (Türkiye)
  • Izmir, Turkey (Türkiye), 35140
    • Izmir Democracy University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age between 10 and 13 years.
• Good general health.
• Fully erupted maxillary premolars.
• Healthy periodontal status, with probing depth of 3 mm or less.
• For the intervention group, a clinical indication for rapid maxillary expansion.
• For the control group, no orthodontic treatment planned during the observation period.
• Ability to comply with the clinical examination and gingival crevicular fluid sampling schedule.
• Written informed consent from the participant's parent or legal guardian and assent from the participant, where applicable.

Exclusion Criteria:

• Systemic disease.
• Current medication use that could influence periodontal, inflammatory, or oxidative status.
• Active periodontal disease.
• Probing depth greater than 3 mm.
• Inability to comply with the oral hygiene protocol or study visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No intervention; Age- and sex-matched participants who did not receive orthodontic treatment during the observation period. Participants underwent the same periodontal examinations and gingival crevicular fluid sampling schedule as the intervention group.
Experimental: Expansion; A tooth-borne rapid maxillary expansion appliance with bands cemented to the maxillary permanent first molars and palatal bars connecting the premolar and molar regions to the expansion screw. The screw was activated twice daily, corresponding to approximately 0.5 mm of expansion per day, until the clinically planned expansion was achieved. The screw was subsequently stabilized with composite resin and the appliance was maintained during the retention period.	Procedure: Expansion group; A tooth-borne rapid maxillary expansion appliance with bands cemented to the maxillary permanent first molars and palatal bars connecting the premolar and molar regions to the expansion screw. The screw was activated twice daily, corresponding to approximately 0.5 mm of expansion per day, until the clinically planned expansion was achieved. The screw was subsequently stabilized with composite resin and the appliance was maintained during the retention period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gingival crevicular fluid malondialdehyde level	Malondialdehyde in gingival crevicular fluid was assessed using a thiobarbituric acid reactive substances method and normalized to total protein concentration. Higher values indicate greater local lipid peroxidation.	Baseline; 24 hours after appliance placement; 7 days after appliance placement; after 7 days of active expansion; after 14 days of active expansion; and after 3 months of retention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gingival crevicular fluid reduced glutathione level	Reduced glutathione was measured spectrophotometrically and normalized to total protein concentration	Baseline; 24 hours after appliance placement; 7 days after appliance placement; after 7 days of active expansion; after 14 days of active expansion; and after 3 months of retention.
Change in gingival crevicular fluid glutathione peroxidase activity	Glutathione peroxidase activity was measured spectrophotometrically and normalized to total protein concentration	Baseline; 24 hours after appliance placement; 7 days after appliance placement; after 7 days of active expansion; after 14 days of active expansion; and after 3 months of retention.
Change in gingival crevicular fluid vitamin C level	Vitamin C was measured using a colorimetric spectrophotometric method and normalized to total protein concentration.	Baseline; 24 hours after appliance placement; 7 days after appliance placement; after 7 days of active expansion; after 14 days of active expansion; and after 3 months of retention.

Collaborators and Investigators

• Sponsor: IRCCS Ospedale San Raffaele
• Collaborators: Università Vita-Salute San Raffaele

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2011
• Primary Completion (Actual): May 31, 2011
• Study Completion (Actual): June 30, 2012

Study Registration Dates

• First Submitted: July 6, 2026
• First Submitted That Met QC Criteria: July 6, 2026
• First Posted (Actual): July 10, 2026

Study Record Updates

• Last Update Posted (Actual): July 10, 2026
• Last Update Submitted That Met QC Criteria: July 6, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Oxidative stress; Gingival crevicular fluid; Rapid maxillary expansion
• Other Study ID Numbers: Oxidative Stress Expansion

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: De-identified individual participant data underlying the published results, together with the data dictionary, may be made available upon reasonable request to the corresponding author and subject to approval by the responsible institution and applicable ethical and data-protection requirements.

Drug and device information, study documents

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