Risk Factors for Osteoradionecrosis After Head and Neck Radiotherapy: A Systematic Review

INTRODUCTION: Although intensity-modulated radiotherapy (IMRT) has led to a significant reduction in mandibular osteoradionecrosis (ORN) rates, head-and-neck radiotherapy (RT) is rapidly evolving-with increasing use of altered schedules and with novel systemic regimens including immune checkpoint inhibitors (ICI). The aim of this work is to systematically review the established risk factors for ORN after head-and-neck RT and to provide a narrative outlook on emerging risk factors. MATERIAL AND METHODS: A systematic review of the literature was performed in September 2025 on three databases (PubMed/MEDLINE, Embase and Scopus), using the MeSH terms "osteoradionecrosis" and "head and neck neoplasm." No language restriction was applied. Studies deemed eligible were studies reporting factors associated with the onset of osteoradionecrosis after photon-based head-and-neck RT. RESULTS: A total of 14 articles were included (1 prospective, 13 retrospective). The proportion of patients who developed ORN ranged from 1.8% to 19.8%, with a median interval from RT to ORN onset of 8 to 40 months. Pre-RT dental extraction (particularly within 7 days before RT start) and higher mandibular dose-volume parameters (V50Gy, V60Gy, dose to the primary site) were consistently associated with ORN onset. Smoking was associated with a shorter time to ORN onset, and bone surgery with resection of the periosteum was a strong independent risk factor (HR 5.87). No included study reported altered fractionation (accelerated, hyperfractionated) as being a risk factor to develop ORN. CONCLUSION: Risk factors for ORN include both patient-related (smoking) and treatment-related (pre-RT dental extraction, mandibular V50Gy/V60Gy) parameters. Whether these risk factors retain their relevance in modern altered-fractionation schedules and in ICI-combination regimens is currently unknown and warrants dedicated analysis from prospective studies.