Key Takeaways & Executive Findings
- •• Articular cartilage lesions in steroid-induced osteonecrosis of the femoral head (SIONFH) are primarily localized to the deep cartilage and calcified cartilage, with severity correlating with the degree of collapse. • Subchondral bone necrosis alters the local microenvironment and elastic modulus, leading to calcified cartilage sclerosis and subsequent brittle fracture at the necrosis-sclerosis junction, initiating the crescent sign. • Granulation tissue invasion from subchondral bone trabecular spaces stimulates chondrocyte terminal differentiation, apoptosis, and matrix degradation, impairing cartilage repair and leading to bone-cartilage separation. • The crescent sign on imaging corresponds to the pathological separation and defect between articular cartilage and subchondral bone, resulting from progressive bone and cartilage fracture and failed integration.
Abstract
BACKGROUND: The crescent sign is a significant radiological feature in the progression of steroid-induced osteonecrosis of the femoral head (SIONFH), indicating the separation and defect of articular cartilage and subchondral bone. The appearance of the crescent sign is associated with the mid-to-late stages of the disease and poor prognosis. However, studies on the specific pathological characteristics and progression patterns of articular cartilage in SIONFH remain unclear. OBJECTIVE: To observe the pathological features of articular cartilage in specimens from different stages of SIONFH, explore the progression and pathological mechanisms, and elucidate the formation mechanism of the crescent sign, providing a theoretical basis for optimizing hip-preserving strategies. METHODS: Femoral head specimens were collected from patients with SIONFH who underwent total hip arthroplasty at the First Affiliated Hospital of Guangzhou University of Chinese Medicine from 2021 to 2024. According to the ARCO staging, they were divided into mild, moderate, and severe collapse groups, with fresh femoral neck fracture specimens as controls. All specimens were cut coronally, and the folded cartilage surface in the necrotic area was taken; control group took corresponding area. Hematoxylin-eosin staining and Safranin O-fast green staining were used for morphological observation, immunohistochemistry and western blot for biomarker expression, and apoptosis kit for apoptosis level. RESULTS AND CONCLUSION: (1) Gross observation: The control group showed smooth cartilage surface without folds or hyperplasia, no separation or defect between articular cartilage and subchondral bone, and tough texture. In SIONFH specimens, obvious folds were visible on the cartilage surface, with separation and defects between articular cartilage and subchondral bone, and a loose sensation on pressing. (2) Pathological observation: In the control group, chondrocytes in each layer were arranged neatly, cartilage matrix stained uniformly, tidemark was intact and continuous, calcified cartilage layer and subchondral bone connection was clear and complete, and bone trabeculae were arranged neatly. In SIONFH specimens, chondrocytes were disorganized, empty lacunae increased, matrix staining loss of varying degrees, tidemark duplication and loss, calcified cartilage layer showed numerous cavities and sclerosis, with granulation tissue invasion into cavities, separation and defects between calcified cartilage and subchondral bone, and abundant proliferative granulation tissue in subchondral bone trabecular spaces. (3) Immunohistochemistry: In SIONFH specimens, positive staining of Runt-related transcription factor 2, matrix metalloproteinase 13, matrix metalloproteinase 3, and collagen type I alpha 2 chain increased in calcified cartilage layer and deep cartilage; vascular endothelial growth factor A, hypoxia-inducible factor 1 alpha, interleukin-1 beta, and tumor necrosis factor alpha positive staining increased in subchondral bone trabecular spaces and deep cartilage granulation and scar tissue. (4) Western blot results showed decreased expression of collagen type II alpha 1 chain and SOX9, and increased expression of Runt-related transcription factor 2, matrix metalloproteinase 13, hypoxia-inducible factor 1 alpha, and vascular endothelial growth factor A in SIONFH specimens. (5) Caspase3/7 activity in SIONFH samples was significantly higher than that in the control group, positively correlated with the degree of collapse. (6) These results indicate that articular cartilage lesions in SIONFH mainly concentrate in the deep cartilage and calcified cartilage around the necrotic area. Necrosis of subchondral bone leads to changes in local microenvironment and elastic modulus, causing sclerosis of calcified cartilage. With continued weight-bearing, stress concentration at the necrosis-sclerosis junction leads to brittle fracture, which is the starting point of fracture. Bone and cartilage fracture leads to destruction of the subchondral cortical bone barrier, and invasion of granulation tissue from subchondral bone trabecular spaces directly stimulates calcified cartilage and deep cartilage, resulting in terminal differentiation, apoptosis, matrix degradation, and cavity formation of chondrocytes, leading to decreased repair capacity of articular cartilage. The diseased cartilage cannot properly interlock with subchondral bone, and with disease progression, extensive separation and defects eventually appear between bone and cartilage, manifesting as the crescent sign on imaging.
1. Introduction
Steroid-induced osteonecrosis of the femoral head (SIONFH) is a common refractory orthopedic disease, frequently seen in patients with autoimmune diseases such as systemic lupus erythematosus and nephrotic syndrome, associated with glucocorticoid use [1-4]. Its pathogenesis is complex, mainly due to altered cellular metabolism and interruption or damage of local blood supply, leading to local tissue destruction. The pathological process involves multiple aspects including articular cartilage, subchondral bone, and bone marrow [5-6]. Currently, there is no effective way to prevent SIONFH from the source [7]. Early progression of SIONFH is insidious; both children and adults may have no obvious subjective symptoms. As the disease progresses to the stage of femoral head collapse, patients experience significant pain and limited mobility, prompting medical consultation, at which point they are often in the mid-to-late stages, making treatment more difficult [8]. Additionally, some patients, due to limited medical resources, may not receive timely diagnosis and treatment.
The crescent sign is a crucial radiological feature in the progression of SIONFH, reflecting the separation and defect of articular cartilage and subchondral bone. Its appearance is associated with the mid-to-late stages of the disease and poor prognosis. However, the specific pathological characteristics and progression patterns of articular cartilage in SIONFH remain unclear. This study aims to observe the pathological features of articular cartilage in specimens from different stages of SIONFH, explore the progression and pathological mechanisms, and elucidate the formation mechanism of the crescent sign, providing a theoretical basis for optimizing hip-preserving strategies.
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Wan Ziyi, Jiang Mengyu, Zhou Yuehui, Xue Yuxuan, Wei Yangwenxiang, Zhou Chi (2026). Articular cartilage lesions at different stages of steroid-induced osteonecrosis of the femoral head: characteristics and mechanisms of crescent sign formation. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21225
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Frequently Asked Questions
What is the crescent sign in steroid-induced osteonecrosis of the femoral head?
The crescent sign is a radiological feature seen on X-ray of the femoral head, appearing as a 2-4 mm wide crescent-shaped radiolucent band beneath the articular surface. It indicates separation and defect between articular cartilage and subchondral bone, associated with the mid-to-late stages of the disease and poor prognosis.
What are the main pathological changes in articular cartilage in steroid-induced osteonecrosis of the femoral head?
The main pathological changes include disorganized chondrocytes, increased empty lacunae, matrix staining loss, tidemark duplication and loss, calcified cartilage sclerosis with cavities, and granulation tissue invasion. These changes are primarily localized to the deep cartilage and calcified cartilage around the necrotic area.
How does the crescent sign form according to this study?
The study suggests that subchondral bone necrosis alters the local microenvironment and elastic modulus, leading to calcified cartilage sclerosis. With continued weight-bearing, stress concentration at the necrosis-sclerosis junction causes brittle fracture, which is the starting point. Bone and cartilage fracture disrupts the subchondral cortical bone barrier, allowing granulation tissue invasion that stimulates chondrocyte terminal differentiation, apoptosis, and matrix degradation, ultimately leading to extensive separation and defect between bone and cartilage, manifesting as the crescent sign.
What biomarkers are associated with the progression of steroid-induced osteonecrosis of the femoral head?
The study found increased expression of Runt-related transcription factor 2, matrix metalloproteinase 13, matrix metalloproteinase 3, collagen type I alpha 2 chain, vascular endothelial growth factor A, hypoxia-inducible factor 1 alpha, interleukin-1 beta, and tumor necrosis factor alpha, while collagen type II alpha 1 chain and SOX9 were decreased. Caspase3/7 activity was also elevated, correlating with the degree of collapse.
What are the clinical implications of this study for hip-preserving strategies?
Understanding the pathological mechanisms of cartilage lesions and crescent sign formation can help in early detection and intervention. It highlights the importance of preserving the subchondral bone integrity and managing the microenvironment to prevent cartilage degeneration and collapse, thereby optimizing hip-preserving strategies.
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