Correlations between Immune Response and Etiopathogenic Factors of Medication-Related Osteonecrosis of the Jaw in Cancer Patients Treated with Zoledronic Acid.

Impairment of the immune response in MRONJ (medication-related osteonecrosis of the jaws) is one of the still unclear etiopathogenic mechanisms of this condition encountered in cancer patients treated with bisphosphonates, with negative effects on the patient's quality of life. The aim of the present study was to correlate the immune response with etiopathogenic factors via immunohistochemical evaluation of the maxillary tissues in zoledronic acid osteonecrosis. The retrospective study included a group of 51 patients with various types of cancers, diagnosed with stage 2 or 3 MRONJ at zoledronic acid and treated surgically. Immunohistochemical expressions of αSMA, CD3, CD4, CD8, CD20, CD79α, CD68, CD204, and tryptase were evaluated. Immunohistochemical markers expressions were statistically analyzed according to the duration of the treatment, the trigger factor, the location of the MRONJ, and the healing status. Analysis of the immune response included T lymphocytes, B lymphocytes, plasma cells, macrophages, and mast cells. The duration of treatment significantly influenced the immunohistochemical expression of most markers (p < 0.05). For an increasing trend in treatment duration, a decreasing trend in marker score was observed, suggesting an inverse correlation. The expression of the markers was different depending on the trigger factor, on MRONJ localization (maxilla/mandible), and the healing status, being more intense in patients cured per primam compared to those who had relapses. The patient's immune response was negatively influenced by the duration of the treatment, the trigger factor, the location of the lesion in the mandible, and the recurrence of MRONJ.

Risk Factors for Medication-Related Osteonecrosis of the Jaw-A Binomial Analysis of Data of Cancer Patients from Craiova and Constanta Treated with Zoledronic Acid.

MRONJ (Medication-Related Osteonecrosis of the Jaw) is a condition observed in a subset of cancer patients who have undergone treatment with zoledronic acid in order to either prevent or treat bone metastases. The primary aim of this research was to establish the importance of risk factors in the development of medication-related osteonecrosis of the jaw in cancer patients receiving zoledronic acid therapy for bone metastases. The present study is an observational retrospective investigation conducted at two university centers, namely, Craiova and Constanța, and included cancer patients treated with zoledronic acid. The medical records of the patients were obtained over a four-year timeframe spanning from June 2018 to June 2022. The data analysis was carried out between January 2021 and October 2022. Patients were treated for cancer, bone metastases, and MRONJ according to the international guidelines. The research investigated a cohort of 174 cancer patients (109 females and 65 males) aged between 22 and 84 years (with a mean age 64.65 ± 10.72 years) seeking treatment at oncology clinics situated in Craiova and Constanța. The study conducted a binomial logistic regression to analyze ten predictor variables, namely, gender, age, smoking status, treatment duration, chemotherapy, radiotherapy, endocrine therapy, presence of diabetes mellitus (DM), obesity, and hypertension (HT). The results of the analysis revealed that only five of the ten predictor variables were statistically significant for MRONJ occurrence: duration of treatment (p < 0.005), chemotherapy (p = 0.007), and hypertension (p = 0.002) as risk factors, and endocrine therapy (p = 0.001) and obesity (p = 0.024) as protective factors.

Clinical and Histopathological Aspects of MRONJ in Cancer Patients.

Medication-related osteonecrosis of the jaw (MRONJ) is a major complication of bisphosphonate treatment in cancer patients, and its etiology is not completely clarified. The study's goal is to find connections between the clinical and histopathological characteristics of osteonecrosis and bisphosphonates in a cohort of cancer patients who had osteonecrosis treated surgically. The retrospective study includes 51 patients of both sexes, aged 46 to 85 years, who underwent surgical treatment for MRONJ in two oral and maxillofacial surgery clinics (Craiova and Constanța). Demographic, clinical, and imaging data from the records of patients with osteonecrosis were analyzed. The surgical treatment removed the necrotic bone, and the harvested fragments were analyzed from a histopathological perspective. The histopathological examination data were evaluated and statistically processed to look for viable bone, granulation tissue, bacterial colonies, and inflammatory infiltrate. In the study groups, MRONJ was found particularly in the posterior regions of the mandible. Tooth extraction, but also periapical or periodontal infections, represented the trigger factors in most of the cases. The surgical therapy consisted of sequestrectomy or bone resection, and the histopathological examination of the fragments revealed osteonecrosis-specific features, such as the lack of bone cells, the development of an inflammatory infiltrate, and the existence of bacterial colonies. MRONJ in cancer patients receiving zoledronic acid is a severe complication that significantly lowers quality of life. Since these patients are not usually monitored by the dentist, they are identified in advanced stages of MRONJ. For these patients, thorough dental monitoring could reduce the incidence of osteonecrosis and its related complications.

Mandibulectomy Reconstruction with Pectoralis Major Island Flap Associated with Primary Reconstruction Plate for Mandibular Medication-Related Osteonecrosis.

A bimaxillary edentulous male patient, aged 67 years, diagnosed with prostate cancer who underwent intravenous bisphosphonates treatment (zoledronic acid) for about one year presented with pain in the anterior mandibular arch, with exposed necrotic bone, and was diagnosed with stage 2 medication-related osteonecrosis of the jaw (MRONJ). MRONJ is the development of bone necrosis in the oral cavity as an adverse reaction in patients treated with antiresorptive and antiangiogenic medication, without radiation therapy to the head and neck. This persistent bone necrosis does not always respond to standard treatments. The reconstruction technique with pectoralis major flap, at a distance, associated with the primary reconstruction plate, was an effective treatment modality for the treatment of large osteonecrosis noncompliant with conservatory treatments. Through this technique, the morpho-functionality of the jaw can be restored almost completely.