Therapeutic Exposures and Risk Factors in MRONJ

Primary outcomes

1. Change in Karnofsky Performance Status

   Time frame: 24 months

   This outcome measures the overall health status and activity levels of patients with MRONJ using the Karnofsky Performance Scale (KPS). KPS rates patients on a scale from 0 to 100, where higher scores indicate greater independence and lower morbidity risk, while lower scores reflect dependency and the need for substantial medical intervention. The scale's aim is to quantify the extent to which patients can perform everyday life activities without assistance. At baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3), 18 and 24 months (T4, if required), the questionnaire will be taken.

2. Change in Oral Health-related Quality of Life

   Time frame: 24 months

   A scale of 1 to 5 will be used to rate each of the 14 questions about how dental health affects quality of life (minimum score of 0, maximum score of 70). Higher ratings reflect a greater influence of the patient's dental health on their quality of life (higher scores, worse outcomes). At baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3), 18 and 24 months (T4, if required), the questionnaire will be taken.

3. Change in staging of MRONJ

   Time frame: 24 months

   Staging of the lesion in the mouth will be according to the definition of the American Association of Oral and Maxillofacial Surgeons (Ruggiero et al. 2022). Clinical examination will be performed at baseline (T0), 3 months (T1), 6 months (T2), 12 months (T3), 18 and 24 months (T4, if necessary).

4. Biochemical Markers Related to Bone Metabolism and Inflammatory Response

   Time frame: Baseline

   Various biochemical markers indicative of bone metabolism and inflammatory response in patients with medication-related osteonecrosis of the jaw (MRONJ) will be evaluated. The markers include serum calcium, ionized calcium, parathyroid hormone (PTH), alkaline phosphatase, osteocalcin, C-telopeptide (CTX), Vitamin D3, C-reactive protein (CRP), and leukocyte count. Blood samples collected at baseline will be analyzed.

5. Change in the Assessment of Radiographic Changes Using the Composite Radiographic Index

   Time frame: 24 months

   This outcome involves utilizing the Composite Radiographic Index to track and characterize the progression of lesions in patients with medication-related osteonecrosis of the jaw. This index evaluates:

   • Location of the lesion: Maxilla anterior, Maxilla posterior, Mandible anterior, Mandibular posterior.
   • Lyric changes: Scored as 0 (None), 1 (Localized), 2 (Widespread).
   • Sclerosis: Scored as 0 (None), 1 (Localized), 2 (Widespread).
   • Periosteal bone formation: Scored as 0 (None), 1 (Localized), 2 (Widespread).
   • Sequestration: Scored as 0 (None), 1 (Localized), 2 (Widespread). Radiographs will be taken at the initial visit to establish a baseline for each patient. Subsequent radiographs will be taken only if clinically indicated to monitor the presence and progression of osteonecrotic lesions.