OZONE_EXO: Comparative Analysis of Protocols for Dental Exactions in Patients at Risk of MRONJ: Case-control Study
Condition: MEDICATION RELATED OSTEONECROSIS OF THE JAW
MeSH terms: Osteonecrosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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: 
      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.
    

Intervention name(s): OxigenOzone_Insufflation
Intervention type(s): Biological
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: MRONJ; Osteonecrosis; Ozone therapy; Jaw; Antiresorptive; Antiangiogenic drugs; Adverse event