## Protocol Section
### Identification Module
**NCT ID:** NCT06420284

**Brief Title:** Immunological Parameters Between MRONJ Stages

**Official Title:** Characterization of Immunological Parameters in Different Clinical Stages of Medication-Related Osteonecrosis of the Jaw

#### Organization Study ID Info
**ID:** MU_DHF_MI_01
#### Organization
**Class:** OTHER
**Full Name:** Marmara University
### Status Module
#### Completion Date
**Date:** 2025-05-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-02-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-14
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Marmara University

#### Responsible Party

**Investigator Affiliation:** Marmara University

**Investigator Full Name:** Ferit Bayram

**Investigator Title:** Assist. Prof.

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** This study aims to conduct a detailed analysis of the immunological response profiles that emerge at different clinical stages of medication-related osteonecrosis of the jaw (MRONJ). The research seeks to understand how these responses influence the pathogenesis, staging, and treatment of MRONJ. Throughout the study, cytokine levels, inflammation markers, and other immunological parameters observed at various stages will be comprehensively assessed. The results of these analyses are expected to provide insights into how stage-specific immunological variables could play a role in the diagnosis and treatment of MRONJ.

### Conditions Module

**Conditions:**

- Medication-Related Osteonecrosis of Jaw

### Design Module

#### Design Info

**Observational Model:** CASE_CONTROL

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 42

**Type:** ESTIMATED

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants in this group are receiving antiresorptive/antiangiogenic therapy and exhibit nonspecific symptoms but no exposed bone. This stage is considered a precursor stage, where the risk of developing MRONJ is present but not yet visible through exposed bone.

**Label:** MRONJ Stage 0

#### Arm Group 2

**Description:** Individuals in this group are on antiresorptive/antiangiogenic therapy and show exposed bone without any symptoms. This stage represents the early manifestation of MRONJ, characterized by visible bone changes without associated pain or infection.

**Label:** MRONJ Stage I

#### Arm Group 3

**Description:** This group includes patients treated with antiresorptive/antiangiogenic agents, who have exposed bone accompanied by symptoms such as pain or infection but without extensive bone involvement. This stage indicates a progression in the severity of MRONJ.

**Label:** MRONJ Stage II

#### Arm Group 4

**Description:** Participants are undergoing antiresorptive/antiangiogenic treatment and exhibit exposed bone with symptoms, where the exposed bone extends beyond the alveolar bone, indicating advanced disease with significant bone and surrounding tissue involvement.

**Label:** MRONJ Stage III

#### Arm Group 5

**Description:** This group consists of individuals receiving antiresorptive/antiangiogenic therapy who do not yet show any exposed bone or symptoms. They are considered at risk for developing MRONJ and are monitored for any potential progression.

**Label:** At-Risk Group

#### Arm Group 6

**Description:** This control group comprises individuals who have not received antiresorptive/antiangiogenic therapy and show no signs of exposed bone or symptoms. This group serves to provide baseline data for comparing immunological parameters against those receiving treatment.

**Label:** Healthy Control Group

### Outcomes Module

#### Primary Outcomes

**Description:** This outcome evaluates the proliferation capacity of peripheral blood mononuclear cells (PBMCs) isolated from the study participants. This analysis will help quantify and understand the dynamics of lymphocyte activation and proliferation in response to different clinical stages of MRONJ and potentially identify immunological differences that could inform therapeutic strategies.

**Measure:** Lymphocyte Proliferation Analysis

**Time Frame:** Baseline

**Description:** This outcome assesses apoptosis in lymphocytes isolated from the peripheral blood of participants included in the study. This analysis aims to quantify apoptotic processes in lymphocytes, offering insights into cell death mechanisms under varying conditions of culture and potentially relating these mechanisms to the immunopathology of MRONJ.

**Measure:** Apoptosis Analysis in Lymphocytes

**Time Frame:** Baseline

**Description:** This outcome measures the levels of specific cytokines as indicators of immunological response in MRONJ at different disease stages. The cytokines to be analyzed include IL-17, IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ.

**Measure:** Cytokine Profile Analysis

**Time Frame:** Baseline

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Individuals aged 18 and over
* Both male and female participants
* Individuals who apply to the Oral and Maxillofacial Surgery Clinic at Marmara University Faculty of Dentistry due to medication-related osteonecrosis of the jaw during the study period
* Individuals or their legal representatives who have provided written consent to participate in the study

Exclusion Criteria:

* Non-drug-related osteonecrosis/osteomyelitis
* Osteoradionecrosis
* Metastasis to the oral region
* Individuals who have not given written consent to participate in the study

**Healthy Volunteers:** True

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**Study Population:** The study population for this research comprises adults aged 18 and older, both male and female, who present with medication-related osteonecrosis of the jaw (MRONJ) at the Oral and Maxillofacial Surgery Clinic of Marmara University Faculty of Dentistry. All participants must have provided written informed consent either personally or through a legal representative to be included in the study.

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ferit.bayram@marmara.edu.tr

**Name:** Ferit Bayram, PhD

**Phone:** 00902167775000

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Istanbul

**Contacts:**

***Contact 1:***

- **Email:** ferit.bayram@marmara.edu.tr

- **Name:** Ferit Bayram, Ph. D.

- **Phone:** 2167775074

- **Role:** CONTACT

***Contact 2:***

- **Name:** Tunç Akkoç, Prof. Dr.

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 3:***

- **Name:** Gül Emren, DDS

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 4:***

- **Name:** Zeynep Tunca

- **Role:** PRINCIPAL_INVESTIGATOR

***Contact 5:***

- **Name:** Sabriye Senem Kılıç

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** Turkey

**Facility:** Marmara University School of Dentistry

**Status:** RECRUITING

**Zip:** 34854

#### Overall Officials

**Official 1:**

**Affiliation:** Marmara University Faculty of Dentistry

**Name:** Ferit Bayram, PhD

**Role:** STUDY_CHAIR

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

### References Module

#### References

**Citation:** Ruggiero SL, Dodson TB, Aghaloo T, Carlson ER, Ward BB, Kademani D. American Association of Oral and Maxillofacial Surgeons' Position Paper on Medication-Related Osteonecrosis of the Jaws-2022 Update. J Oral Maxillofac Surg. 2022 May;80(5):920-943. doi: 10.1016/j.joms.2022.02.008. Epub 2022 Feb 21.

**PMID:** 35300956

#### See Also Links

**Label:** AAOMS MRONJ staging

**URL:** https://www.aaoms.org/docs/govt_affairs/advocacy_white_papers/mronj_position_paper.pdf

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001847

- Term: Bone Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000009336

- Term: Necrosis

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M12943

- Name: Osteonecrosis

- Relevance: HIGH

- As Found: Osteonecrosis

- ID: M5126

- Name: Bone Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12284

- Name: Necrosis

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000010020

- Term: Osteonecrosis

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M22318

- Name: Angiogenesis Inhibitors

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
