Medication-related osteonecrosis of the jaw (MRONJ), according to the American Association of Oral and Maxillofacial Surgeons (AAOMS), is defined by the presence of exposed, necrotic bone that persists for more than eight weeks in patients who have received or are currently receiving anti-resorptive drug therapy without a history of radiation therapy (Ruggiero et al., 2022a). This condition causes significant pain and suffering for affected individuals. Clinical grading is still used as the primary method for diagnosing MRONJ, yet it might occur too late for early diagnosis and prevention (Gadiwalla and Patel, 2018; Park et al., 2019). A confounding or concealing medical and drug history may result in diagnostic omissions or misunderstandings. Given that mineral loss becomes apparent only after a significant reduction of more than 30 %–50 %, early-stage diagnosis through panoramic radiography (PANO) or cone-beam computed tomography (CBCT) is challenging without normal imaging features for comparison (Koth et al., n.d.). Therefore, the diagnosis of MRONJ at its initial stage is the most difficult and important aspect of its treatment.

Bisphosphonate (BIS) and denosumab are the two medications most frequently associated with MRONJ. These medications are typically recommended by oncologists and orthopedists to prevent bone metastasis and osteoporosis (Baba et al., 2018). Series of position papers on MRONJ consistently highlighting inflammation or infection as a major cause of MRONJ (Ruggiero et al., 2009, 2014, 2022b). The colonization of bacteria on exposed necrotic bone is recognized to exacerbate disease severity (Mawardi et al., 2011). Recent next-generation sequencing studies (Choi et al., 2025) have identified a distinct microbial profile (e.g., S. constellatus and T. forsythia) in MRONJ patients, suggesting potential synergistic interactions in pathogenesis. However, the infection-based hypothesis does not fully account for all clinical presentations of MRONJ. It has been found that most reported MRONJ cases were limited to the jawbones and craniofacial bones rather than the long bones (Wang et al., 2019). Despite shared exposure to the oral environment, MRONJ develops more frequently in the mandible (75 % of cases) than the maxilla (25 %) (Hallmer et al., 2018; Saad et al., 2012). More specifically, MRONJ predominantly manifests in the jawbone adjacent to the alveolar bone rather than in the condyle (Son et al., 2020). Recently, the functional differences between craniofacial bones and long bones in developmental and pathological state has become a research hotspot (Koh et al., 2024). Given the distinct mechanisms of bone formation—in which alveolar bone undergoes intramembranous ossification and the condyle undergoes endochondral ossification—we hypothesized that the type of bone formation may serve as a previously overlooked factor that contributes to the development of MRONJ (B et al., 2021; Ding et al., 2022; L et al., 2023; Zhao et al., 2008).

Osteogenesis is closely connected with the growth of blood vessels during the development of the mammalian skeletal system (Ap et al., 2014). The formation of blood vessels is necessary for osteogenesis, especially a distinct capillary subtype called type H, which has a high expression of the endothelial markers CD31 and endomucin (CD31hi Emcnhi). This subtype plays a crucial role in coupling angiogenesis with osteogenesis (Chen et al., 2023; Xu et al., 2023). On the one hand, zoledronic acid treatment could induce MRONJ observed in the mouse model by disrupting the abundance of the type H vessels in a tooth extraction socket (Shen et al., 2022). On the other hand, alendronate treatment has been demonstrated to significantly promote blood vessel growth in the long bones (Sg et al., 2019). At first glance, these data may seem contradictory, and the underlying cause of this discrepancy is not immediately clear. However, this finding could potentially elucidate the lower incidence of MRONJ in the condyle.

The objective of this research was to initially illustrate the dispersion of the type H vessels in various regions of the jawbone following BIS administration. Consequently, we designed a clinical retrospective cross-sectional study to propose and validate a novel imaging technique for early-stage MRONJ screening. This method is based on the observed disparities in the distribution of the type H vessels within the alveolar bone, jawbone, and temporomandibular regions, alongside alterations in bone mineral density.