OBJECTIVES: Temporomandibular joint osteoarthritis (TMJ-OA) with condylar resorption is a multifactorial condition involving hormonal imbalance and articular disk dysfunction, often leading to severe TMJ degeneration. This study investigated the combined effects of estrogen deficiency and anterior articular disk derangement (ADD) on condylar bone resorption in a mouse model. METHODS: Female C57BL/6J mice underwent ovariectomy (OVX) to induce estrogen deficiency and ADD was surgically induced for stress. The animals were divided into the control, OVX, ADD, and OVX + ADD groups. Microcomputed tomography and histological analyses were conducted to evaluate condylar bone structure, trabecular architecture, and osteoclast activity. RESULTS: OVX and ADD caused significant condylar bone loss, characterized by reduced bone volume per tissue volume (BV/TV) and abnormal trabecular architecture. The OVX + ADD group exhibited exacerbated bone resorption, with decreased BV/TV and increased trabecular separation compared to OVX or ADD alone. Histological analyses revealed increased osteoclast activity in the OVX + ADD group, suggesting a synergistic effect of estrogen deficiency and ADD on condylar degradation. CONCLUSION: Estrogen deficiency amplifies the bone-resorptive and inflammatory effects of ADD, accelerates temporomandibular joint (TMJ) degeneration, and underscores the interplay between hormone imbalance and articular disk dysfunction in the pathophysiology of TMJ-OA. There is a need for integrated treatment strategies, such as effective hormone replacement therapy and articular disk repositioning, to effectively manage temporomandibular joint disorders, particularly in postmenopausal women or those with hormonal imbalances. Further research is required to elucidate these molecular pathways and evaluate long-term therapeutic interventions.