Medication-Related Osteonecrosis of the Jaw: A Cross-Sectional Study on the Prevalence of Cutaneous Manifestations and the Primary Care Physician's Role in its Early Diagnosis

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients undergoing treatment with bone-modifying agents (BMA) for cancer or osteoporosis. Although most cases are treated by oral medicine specialists, some cases may present extraorally as a fistula in the skin or erythematous swelling localized to the jaw area, causing these patients to consult a primary care physician. This study examined the prevalence and clinical characteristics of extraoral manifestations of MRONJ in a large cohort to raise awareness among primary care physicians of this entity, enabling prompt diagnosis and treatment. Methods: Medical records were retrieved of patients diagnosed with MRONJ between 2003 and June 2020 in the Oral Medicine Unit of The Sheba Medical Center, Israel. Data relating to demographics, medical background, type of BMA, and clinical presentation were collected. Results: In total, 515 patients (378 women [73%] and 137 men [27%]; mean age: 65 years, range: 32-94 years) met the inclusion criteria, among whom 84 (16.5%) presented with extraoral manifestations of MRONJ. Of these 84 patients, 21 (24.7%) presented with extraoral fistulas. Extraoral manifestations were strongly correlated with MRONJ of the mandible (n = 67; P = .0006). Conclusions: MRONJ is a significant side effect of BMA therapy. Although MRONJ mostly presents intraorally, some patients may initially present with extraoral manifestations of erythematous swelling or fistulas localized to the jaw area. Primary care physicians should consider MRONJ as a differential diagnosis in such patients.