A Molecular Troika of Angiogenesis, Coagulopathy and Endothelial Dysfunction in the Pathology of Avascular Necrosis of Femoral Head: A Comprehensive Review

Abstract

Avascular necrosis of the femoral head (ANFH) is a painful disorder characterized by the cessation of blood supply to the femoral head, leading to its death and subsequent joint collapse. Influenced by several risk factors, including corticosteroid use, excessive alcohol intake, hypercholesterolemia, smoking and some inflammatory disorders, along with cancer, its clinical consequences are thrombus formation due to underlying inflammation and endothelial dysfunction, which collaborates with coagulopathy and impaired angiogenesis. Nonetheless, angiogenesis resolves the obstructed free flow of the blood by providing alternative routes. Clinical manifestations of early stage of ANFH mimic cysts or lesions in subchondral bone, vasculitis and transient osteoporosis of the hip, rendering it difficult to diagnose, complex to understand and complicated to cure. To date, the treatment methods for ANFH are controversial as no foolproof curative strategy is available, and these depend upon different severity levels of the ANFH. From an in-depth understanding of the pathological determinants of ANFH, it is clear that impaired angiogenesis, coagulopathy and endothelial dysfunction contribute significantly. The present review has set two aims, firstly to examine the role and relevance of this molecular triad (impaired angiogenesis, coagulopathy and endothelial dysfunction) in ANFH pathology and secondly to propose some putative therapeutic strategies, delineating the fact that, for the better management of ANFH, a combined strategy to curtail this molecular triangle must be composed rather than focusing on individual contributions.

Keywords

• avascular necrosis of femoral head
• impaired angiogenesis
• coagulopathy
• endothelial dysfunction
• bone disease
• skeletal abnormality