Introduction

Cancer remains one of the leading causes of death worldwide. In 2022, approximately 20 million new cancer cases and 9.7 million cancer-related deaths were estimated [1]. Among head and neck malignancies, oral cavity cancer is particularly relevant due to its high prevalence, ranking eighth among the most common cancers worldwide [2].

Surgical resection remains the treatment of choice for oral cavity cancer and is often followed by adjuvant radiotherapy in patients with locoregional nodal metastasis. When surgery is not feasible or is insufficient, particularly in extensive tumors or lesions involving critical anatomical structures, combined radiotherapy and chemotherapy may be required [3–5]. Although radiotherapy is oncologically effective, it is associated with a high risk of late local complications, especially involving the maxillofacial bones.

Radiotherapy-related adverse effects include mucositis, dysgeusia, xerostomia with hyposalivation, trismus, increased susceptibility to opportunistic infections, and, in more severe cases, osteoradionecrosis of the jaws (ORNJ) [6, 7]. ORNJ is regarded as one of the most serious complications of radiotherapy in patients with head and neck malignancies. It is characterized by exposed devitalized bone in the oral cavity that persists for more than three months, in the absence of active or recurrent neoplastic disease [8–10]. The mandible is the most commonly affected site, especially in areas receiving radiation doses above 60 Gy [9, 10].

Although the precise pathophysiological mechanisms underlying ORNJ remain incompletely understood, its pathogenesis has been associated with the interplay among ionizing radiation, hypoxia, hypovascularization, and bone hypocellularity, which collectively impair bone remodeling and contribute to progressive necrosis [11, 12]. Clinically, ORNJ may manifest as persistent pain, bone sequestration, secondary infection, fistula formation, ulceration, and pathological fractures, leading to substantial morbidity and markedly impaired quality of life [10, 13, 14].

Several risk factors have been associated with the development of ORNJ. Among treatment-related factors, total radiation dose, the volume of irradiated bone, the radiotherapy technique, and the location of the primary tumor are particularly relevant [15, 16]. Local factors, including bone trauma caused by tooth extractions performed before, during, or after radiotherapy, poorly fitting prostheses, inadequate oral hygiene, active periodontal disease, and odontogenic infections, also contribute substantially to the pathogenesis of ORNJ [13]. In addition, systemic factors such as diabetes mellitus, arteriopathies, alcoholism, and malnutrition may increase the risk of disease development by impairing vascularization and tissue repair capacity [17, 18].

Despite advances in radiotherapy techniques, including intensity-modulated radiotherapy (IMRT), recent evidence suggests that technical improvements alone have not been sufficient to substantially reduce the incidence of ORNJ [19]. This reinforces the multifactorial complexity of the disease and highlights the need for a deeper understanding of its predisposing factors. On imaging, ORNJ may manifest as bone sequestration, sclerosis, periosteal bone formation, delayed alveolar healing, involvement of the inferior alveolar nerve canal, and, occasionally, sinus alterations [20]. Nevertheless, studies that consistently correlate these imaging findings with risk factors implicated in the development of ORNJ remain limited.

Given the lack of consensus regarding optimal strategies for preventing, predicting, and treating ORNJ, identifying and understanding the risk factors associated with its occurrence is essential [21–24]. Therefore, this study aimed to perform a systematic review and meta-analysis to identify risk factors associated with the development of ORNJ.