Advances in mechanism and management of bone homeostasis in osteonecrosis: a review article from basic to clinical applications

Abstract

Osteonecrosis, characterized by bone cell death leading to impaired bone recovery, causes challenges in bone homeostasis maintenance. Bone homeostasis relies on the delicate balance between osteoclasts and osteoblasts, encompassing a series of complex and strictly regulated biological functions. Current treatments, including conservative therapies and surgeries, often fall short of expected outcomes, necessitating a reorientation towards more effective therapeutic strategies according to the pathogenesis. In this review, the authors hierarchically outlined risk factors, emerging mechanisms, and last-decade treatment approaches in osteonecrosis. By connecting mechanisms of bone homeostasis, the authors proposed future research directions should be focused on elucidating risk factors and key molecules, performing high-quality clinical trial, updating practice, and accelerating translational potential.

Figure 1

Study selection.

Figure 2

Overview of bone homeostasis and development of lineages. The delicate balance of bone homeostasis is accomplished by the actions of two types of cells: the osteoblast lineage and osteoclast lineage cells. Osteoblast lineage cells play a role in bone mineralization and the creation of osteocytes by excreting hydroxyapatite and calcium. In contrast, osteoclast lineage cells are involved in bone resorption.

Figure 3

Phenotypes and molecular mechanisms of bone cells and vessels related to osteonecrosis. Osteonecrosis is a complex disease. Besides immune and inflammation factors, increased cell senescence, and fibrosis, it mainly involves the apoptosis of osteoblasts and osteocytes, adipogenic differentiation of BM-MSCs, and the dysfunction of osteoclasts and BM-MSCs with the existence of risk factors (e.g., the use of glucocorticoids). Moreover, hematology impairment also contributes to the progress and inhibits the AKT signaling pathway in osteoblasts. BM-MSC, bone marrow-derived-mesenchymal stromal cell; GC, glucocorticoids.

Figure 4

Current prevention and treatment of osteonecrosis. BMAC, bone marrow aspirate concentrates; BM-MNCs, bone marrow-derived mononuclear cells; CD, core decompression; HBOT, hyperbaric oxygen therapy; PRP, platelet-rich plasma; THA, total hip arthroplasty.

Figure 5

Limitations and future directions of osteonecrosis. EVs, extracellular vehicles; MSCs, mesenchymal stromal cells; RCT, randomized controlled trials; tFNAs, tetrahedral framework nucleic acids.