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.

Osteonecrosis as a rare musculoskeletal complication in Behcet’s disease- the largest case series with literature review

“…In the study by Elgengehy et al Vasculitis damage index in BD patients is significantly associated with ON [ 22 ]. Vascular damage and impaired endothelial dysfunction play different role in development of ON [ 23 ]. So cumulative effect of vasculitis and high dose corticosteroid in these patients may be considerable in ON occurrence.…”

A Comprehensive Review of COVID-19-Infection- and Steroid-Treatment-Associated Bone Avascular Necrosis: A Multi-Study Analysis

“…Moreover, pro-inflammatory proteins cause vasculitis, hypercoagulability, and bone necrosis, and the result can be avascular necrosis (AVN) [1]. More specifically, a state of disrupted molecular pathways exists that consists of endothelial dysfunction, coagulopathy, and impaired angiogenesis, which lead to the initiation and progression of bone ischemia [2]. Concerning the endothelial dysfunction, the balance between vasodilation and vasoconstriction is affected, causing ischemia and disrupted blood flow and thrombi.…”

“…Further research with larger cohorts and long-term follow ups is needed, to better understand the causative relationship and optimal management strategies for hip AVN in the context of COVID-19 and steroid therapy. initiation and progression of bone ischemia [2]. Concerning the endothelial dysfunction, the balance between vasodilation and vasoconstriction is affected, causing ischemia and disrupted blood flow and thrombi.…”

Implications of siRNA Therapy in Bone Health: Silencing Communicates

“…Processes of bone repair, regeneration, and healing are vital for the maintenance of skeletal integrity, mobility, and overall health. Despite these mechanisms remaining in place, many times bone repair and regeneration fail to match the degree of destruction and damage to bone tissue due to several reasons, including impaired angiogenesis, persistent generation of reactive oxygen species (ROS), endothelial dysfunction, dysregulated neutrophils, uncontrollable inflammation, and stem cell dysfunction [3][4][5][6]. However, the primary reason for this perturbed homeostasis of bone repair is the intricate interactions and cross-talks of signaling pathways that induce an unmanageable auto-immune response [5].…”