OZONE_EXO: Comparative Analysis of Protocols for Dental Exactions in Patients at Risk of MRONJ: Case-control Study

Study Overview
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Brief Summary
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Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction of antiresorptive and antiangiogenic agents; it is also a potentially painful and debilitating condition. Today, no specific studies have prospectively evaluated the efficacy of its treatment and no robust standard of care has been established. Among non-invasive procedures to treat MRONJ, the use of medical ozone (O3) arises for its properties and has been deployed and evaluated. O3 has generally proven to play a role in the treatment of chronic, nonhealing, or ischemic wounds, due to its antimicrobial and anti-oxidant properties and to bio-stimulation; it has been extensively used for different medical approaches and purposes. In oral cavity, local applications are carried out by ozonized water (i.e. spray or compress) or gel. The aim of this study was to carry out a case-control study in order to compare two different protocols of dental extractions in patients at risk of MRONJ, with and without infiltration of a mixture of oxygen-ozone. All the cases in our study are cancer and oncologic and osteometabolic patients undergoing high-risk therapy for MRONJ (antiresorptive and antiangiogenic drugs) who require dental extractions with a poor prognosis. During the first examination (T0), medical, pharmacological, and dental history of patients are recorded. Data collected are: (1) age; (2) gender; (3) indications for use, type, cumulative dose and duration of MRONJ-related drugs; (4); history of chemotherapy; (5) other medications; (6) other diseases; (7) smoking. For each patient, an orthopantomography and a cone beam computed tomography of the teeth are performed only if indicated.

Detailed Description
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The enrolled patients were randomly divided into two groups: Group A: consisting of 38 patients (undergoing ozone treatment) (OZONE_EXO) intra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site in patients at risk of medication-induced osteonecrosis of the jaw (ONJ). Group B: comprising 79 controls (not undergoing ozone treatment).(NO_OZONE_EXO) Tooth extraction in patients at risk of medication-induced osteonecrosis of the jaw (ONJ) without the use of ozone application. Following the same approach as in Group A, patients in Group B underwent additional follow-up visits at T1 (3-5 days), T2 (14 days), and T3 (6 weeks) post-extraction, in accordance with Inflammatory - P roliferative - Remodeling (IPR) Wound Healing Scale. the IPR scale score, to meticulously monitor surgical wound healing and record pain intensity using the NRS scale, rather than the originally planned VAS scale, for enhanced ease of use [22]. The IPR scale provided a comprehensive assessment of wound healing through distinct subscales, each ranging from 0 to 1, resulting in a total score ranging from 0 to 16. These subscales evaluated the inflammatory response, proliferative response, and remodeling process. At the conclusion of the follow-up period, the total IPR score was computed, with scores spanning from 0 to 16. Scores of 0-4 denoted poor healings, scores of 5-10 indicated acceptable healing, while scores of 11-16 suggested excellent healing.

Official Title
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Comparative Analysis of Different Protocols for Dental Exactions in Patients at Risk of MRONJ: Case-control Study

Conditions
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MEDICATION RELATED OSTEONECROSIS OF THE JAW

Intervention / Treatment
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* Biological: OxigenOzone_Insufflation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age ≥ 18 yrs patients at risk of developing MRONJ for previous or current administration of drugs related extraction of teeth with a poor prognosis due to severe decay and/or periodontitis Exclusion Criteria: previous radiation in the head and neck area neoplastic involvement of the jaw previous MRONJ diagnosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A (OZONE_EXO)<br>intra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site in patients at risk of medication-induced osteonecrosis of the jaw (ONJ). | Biological: OxigenOzone_Insufflation<br>* intra-tissutal perialveolar injections of a 15-mL mixture of OxigenOzone (O2O3) with a 26Gx 1⁄2 - 0.45x13 mm needle and insufflation of the same mixture in the post-extraction site for at least 1 minute, hemostasis, and suture.<br>|
| No Intervention: Group B (NO_OZONE_EXO)<br>Tooth extraction in patients at risk of medication-induced osteonecrosis of the jaw (ONJ) without the use of ozone application. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healing Evaluation using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Inflammatory Phase | The inflammatory phase is evaluated 3-5 days after tissue injury on the basis of eight parameters, measured on a 9-point scale (0-8): bleeding (spontaneously or on palpation), granulation tissue, hematoma, tissue color, incision margins, suppuration, edema, and pain. A score of 5-8 indicates a successful inflammatory phase | 3-5 days after the intervention | 
| Healing Evaluation using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Proliferative Phase: | The proliferative phase is evaluated 14 days after tissue injury on the basis of five parameters, measured on a 6-point scale (0-5): re-epithelialization, tissue color, scar, suppuration, and pain. A score of 3-5 score indicates successful healing. | 14 days after the intervention | 
| Healing Evaluation using Inflammatory-Proliferative-Remodelling Scale (IPR Scale): Remodelling Phase | The remodeling phase is evaluated 6 weeks after tissue injury on the basis of three parameters, measured on a 4-point scale (0-3): scar, tissue color, and pain. A score of 2-3 indicates successful healing | 6 weeks after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healing Evaluation using IPR Scale: Total process | The total score of the IPR scale ranges from 0 to 16:0-4 indicates poor healing; 5-10, acceptable healing; and 11-16, excellent healing The inflammatory phase carries the greatest weight in the final score because its impairment can jeopardize the entire series of biologic events leading to early wound healing. | 6 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRONJ, Osteonecrosis, Ozone therapy, Jaw, Antiresorptive, Antiangiogenic drugs, Adverse event