Medication-related osteonecrosis of the jaw (MRONJ) is a condition that can occur in patients who take medications such as antiresorptive drugs for osteoporosis and other bone-related systemic diseases. Although the overall risk is relatively low, the number of affected patients is increasing as the population ages and dental implants are increasingly used to restore chewing function. When MRONJ develops at an implant site, deciding whether to keep or remove the implant becomes a difficult clinical problem.

Current treatment recommendations for MRONJ are mainly based on disease stage. However, in situations where only part of the bone around an implant is affected, and the entire implant surface is not involved, there are no clear, evidence-based criteria to guide the decision between implant retention and implant removal. Some clinicians recommend removing all implants associated with necrotic bone to reduce the risk of recurrence. Others attempt to preserve implants that appear less severely affected. Implant retention may carry a risk of delayed healing or recurrence, whereas implant removal may cause additional surgical trauma that could potentially worsen the condition. Therefore, more objective criteria are needed to support clinical decision-making.

In peri-implantitis, another disease affecting the tissues around implants, the amount of bone loss observed on radiographs is often used as a reference for treatment decisions. Traditionally, implant removal has been considered when bone loss reaches approximately 50-60% of the implant length. When bone loss is less extensive, treatment aimed at preserving the implant may be attempted. However, it is unknown whether a similar bone loss threshold applies to patients with implant-related MRONJ.

The purpose of this prospective study is to evaluate whether the extent of peri-implant bone loss-particularly within the range of 20% to 60% of the implant length-can serve as a practical reference for deciding whether to retain or remove an implant in patients with implant-related MRONJ. By comparing clinical outcomes between implant retention and implant removal within this range of bone loss, this study aims to determine whether a bone-loss-based criterion can support treatment decisions.

The primary outcome of the study is complete mucosal healing at 6 months after treatment. Additional outcomes, including radiographic changes assessed by cone-beam computed tomography (CBCT) and recurrence of MRONJ-related clinical signs, will also be evaluated during the 1-year follow-up period after treatment initiation. CBCT imaging will be performed at 6 and 12 months after treatment to assess bone changes over time. Approximately 50 patients will be enrolled in this single-center prospective study. The findings are expected to provide structured clinical data to guide implant management decisions in patients with implant-related MRONJ.

This is a single-center, prospective study conducted at Kyung Hee University Dental Hospital that compares clinical outcomes between implant retention and implant removal in patients diagnosed with implant-related medication-related osteonecrosis of the jaw (MRONJ).

1. Background and Rationale:

   Implant-related MRONJ presents a significant clinical challenge in patients receiving antiresorptive therapy. Although both implant retention and implant removal are currently used as treatment strategies, there is insufficient prospective evidence to compare their clinical effectiveness. Most available data are retrospective and heterogeneous. Therefore, a prospective study is needed to generate structured clinical outcomes and to inform future large-scale comparative research.

2. Study Population:

Eligible participants are adult patients diagnosed with implant-related MRONJ according to established diagnostic criteria. Diagnosis will be based on clinical findings, radiographic evaluation, and the history of the antiresorptive agent. Patients who meet the inclusion criteria and provide informed consent will be prospectively enrolled. Participants with peri-implant MRONJ involving implants with baseline peri-implant bone loss between 20% and 60% on CBCT will be enrolled. Treatment outcomes of implant retention versus removal will be compared to inform decision criteria within this bone-loss range. If multiple implants are involved within a single MRONJ lesion, all affected implants will be included in the analysis.

3) Study Design and Intervention:

1. Implant Retention Group:

   The affected implant will be preserved, and patients will receive conservative management to control infection, remove necrotic bone as indicated, and promote soft-tissue healing. In the implant retention arm, if intraoperative assessment reveals peri-implant bone loss exceeding 60% of the implant length or compromised implant stability, conversion to implant removal may be performed in accordance with predefined protocol criteria.

2. Implant Removal Group:

The affected implant will be surgically removed, followed by appropriate debridement and management of the site to promote resolution of necrotic bone and soft-tissue healing.

Treatment allocation will not be randomized. Decisions will be made based on clinical assessment, disease severity, patient preference, and shared decision-making between the patient and the clinician.

4) Outcome Measures:

1. Primary Outcome:

   The primary endpoint is complete mucosal healing at 6 months after treatment. Complete mucosal healing is defined as full coverage of the previously exposed bone area with intact mucosa and absence of clinical signs of active infection.

2. Secondary Outcomes:

   • Radiographic marginal bone changes will be assessed using CBCT at 6 and 12 months after treatment. The 6-month CBCT will serve as the reference image after initial healing. Marginal bone changes within approximately 1.0-1.5 mm will be considered physiologic remodeling; greater bone loss will be interpreted as radiographic progression of MRONJ.

   • Recurrence or persistence of MRONJ-related clinical signs and symptoms, including fistula formation, gingival swelling, erythema, suppuration, or exposed bone, during the 1-year follow-up period.

     5) Sample Size and Study Purpose: Approximately 50 patients are expected to be enrolled. As a prospective study, the primary aim is to generate prospective clinical data and evaluate feasibility, clinical trends, and outcome variability. The findings will inform the design and sample size estimation for future larger comparative studies.

     6) Ethical Considerations: This study has been reviewed and approved by the Institutional Review Board of Kyung Hee University Dental Hospital. All participants will provide written informed consent prior to enrollment.

     7) Study Significance: By prospectively comparing implant retention and removal in implant-related MRONJ, this study aims to clarify patterns of clinical outcomes and provide evidence to support decision-making in the management of this complex condition.

Inclusion Criteria:

• Patients diagnosed with medication-related osteonecrosis of the jaw (MRONJ) (AAOMS stage 0, 1, or 2) who have been treated with antiresorptive agents (e.g., bisphosphonates or denosumab) and/or selective estrogen receptor modulators (SERMs).
• Presence of an MRONJ lesion involving at least one dental implant at the affected site.
• Radiographic peri-implant bone loss between ≥20% and <60% of the implant length at the most severe area on baseline imaging.
• No implant mobility.
• Able and willing to provide written informed consent after receiving an adequate explanation of the study purpose and procedures.

Exclusion Criteria:

• History of radiotherapy to the head and neck region.
• Presence of metastatic disease or bone diseases such as multiple myeloma or Paget's disease of the jaw.
• Current treatment with anti-angiogenic agents (e.g., bevacizumab, ranibizumab, lenalidomide, sunitinib) or immunomodulatory agents (e.g., methotrexate) for cancer therapy.
• Uncontrolled systemic disease that may contraindicate surgery or impair healing (e.g., uncontrolled diabetes, recent chemotherapy, severe immunosuppression).
• Refusal of treatment or follow-up, withdrawal of consent, or inability to comply with study procedures.
• Peri-implant bone loss outside the predefined range (<20% or ≥60%) on preoperative imaging or intraoperative assessment.

Individual participant data (IPD) will not be shared due to the small sample size and the inclusion of imaging data, which may increase the risk of participant re-identification. Data sharing was not included in the IRB-approved protocol.