Classical non-traumatic osteonecrosis versus osteonecrosis of the jaw: Distinct manifestations of a shared pathophysiological spectrum.

Abstract

Classical non-traumatic osteonecrosis (NTON)-most commonly affecting the femoral head-and osteonecrosis of the jaw (ONJ) represent two major forms of osteonecrosis. Ongoing debate persists regarding whether these conditions reflect manifestations of a shared underlying pathology or represent distinct clinical entities. We hypothesize that although NTON and ONJ share core mechanisms, their initiating events, osteoclastic responses, and reactions to anti-resorptive therapy differ sufficiently. A comprehensive literature review was conducted using PubMed, Scopus, Web of Science, and the Cochrane Library. Evidence was synthesized regarding anatomical and mechanical differences, etiologic factors, pathogenic mechanisms, and therapeutic responses in NTON and ONJ. In NTON, compromised vascular supply is widely recognized as the primary initiating event, leading to hypoxia, increased osteoclastogenesis, and excessive bone resorption. In ONJ, impaired blood flow occurs secondarily, typically following dental trauma, infection, or anti-resorptive therapy. While both conditions involve disturbed bone homeostasis, NTON is characterized by heightened osteoclast activity, whereas ONJ features suppressed osteoclast function. This contrast results in divergent pharmacologic behavior: bisphosphonates and denosumab may be protective during the resorptive stage of NTON but significantly increase the risk of ONJ. Although NTON and ONJ share fundamental disruptions in bone homeostasis and vascular regulation, their distinct initiating events, osteoclastic dynamics, and responses to anti-resorptive therapy suggest they are best viewed as separate clinical entities rather than variations of a single disease.