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

Abstract

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.

Affiliated Institutions

• Zhongshan Hospital of Xiamen University CN
• Wangjing Hospital of China Academy of Chinese Medical Sciences CN
• First Affiliated Hospital of Wenzhou Medical University CN
• Wenzhou Medical University CN
• Chinese Academy of Medical Sciences & Peking Union Medical College CN

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