Senescence-driven osteonecrosis of the femoral head in the elderly—a distinct pathophysiological entity

This article conceptualizes "Senescence-Driven Osteonecrosis of the Femoral Head" in elderly patients as a distinct pathophysiological entity, differing from classic osteonecrosis of the femoral head (ONFH) by its primary age-related etiological factors. It hypothesizes that this condition arises from a convergence of vascular fragility, impaired bone mechanoadaptation, and systemic inflammaging. Epidemiological patterns reveal under-recognition and diagnostic delays, with presentations often mimicking osteoarthritis. The manuscript examines endothelial cell senescence, microvascular dysfunction, increased bone marrow adiposity-reducing perfusion and osteogenic capacity-and chronic inflammation in the aging femoral head. Emerging omics and biomechanical evidence, including subchondral insufficiency fractures, highlight molecular and structural differences contributing to collapse. Conventional joint-preserving treatments often fail in older individuals, prompting exploration of novel therapies like senolytics, vasculoprotective agents, and early mechanical support. This work advocates for a new framework integrating geriatric comorbidities and senescence biology for tailored diagnosis, prevention, and treatment of this debilitating condition.