• Molecules and Cells
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• v.24 no.3
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• pp.388-393
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• 2007

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease to which certain individuals are more at risk. Altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. Peroxisome Proliferator-Activated Receptor-${\gamma}$ ($PPAR{\gamma}$) plays a crucial role in differentiation of mesenchymal cells to adipocytes, lipid homeostasis, and bone metabolism. To investigate the possible association between $PPAR{\gamma}$ gene variants and susceptibility to ONFH, we genotyped three common polymorphisms (-796A > G, +34C > G[Pro12Ala], and +82466C > T[His477His]) in 448 ONFH patients and 336 control subjects. Genotypes, allele frequencies, and haplotypes of the polymorphisms in the complete set of patients as well as in subgroups by sex or etiology were not significantly different from those in the control group. This suggests that the examined polymorphisms and haplotypes of the $PPAR{\gamma}$ gene are unlikely to be associated with susceptibility to ONFH.

• International Journal of Stem Cells
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• v.15 no.2
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• pp.195-202
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• 2022

Background and Objectives: Apoptosis is an outstanding determinant of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Human umbilical cord mesenchymal stem cells (hUC-MSCs) have been demonstrated to be associated with apoptosis in diseases models. However, the role of hUC-MSCs in GC-induced ONFH via regulating apoptosis still needs further study. Methods and Results: In the present study, a GC-induced ONFH model was built in vivo through a consecutive injection with lipopolysaccharide (LPS) and methylprednisolone. The necrosis and apoptosis of the femoral head was evaluated by histological and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay. The level of collagen and TRAP positive cells were determined by Masson and TRAP staining, respectively. M1 macrophage polarization was assessed using immunofluorescence assay. The level of proinflammatory cytokines including tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and IL-6 of femoral head was determined by enzyme-linked immunosorbent assay (ELISA) kits. The protein expression of AKT, mTOR, p-AKT and p-mTOR was detected using western blot assay. The results showed that hUC-MSCs treatment prominently promoted the GC-induced the decrease of the collagen level and the increase of TRAP positive cells. Besides, hUC-MSCs treatment decreased necrosis and apoptosis, macrophage polarization, the level of TNF-α, IL-1β and IL-6, the protein expression of p-AKT and p-mTOR, and the radio of p-AKT to AKT and p-mTOR to mTOR of femoral head in vivo. Conclusions: Therefore, the present study revealed that hUC-MSCs improved the necrosis and osteocyte apoptosis in GC-induced ONFH model through reducing the macrophage polarization, which was associated with the inhibition of AKT/mTOR signaling pathway.

• Korean Journal of Radiology
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• v.22 no.12
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• pp.2026-2033
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• 2021

Objective: The aim of this study was to compare the diagnostic performances of digital tomosynthesis (DTS) and conventional radiography in detecting osteonecrosis of the femoral head (ONFH) using computed tomography (CT), as the reference standard and evaluate the diagnostic reproducibility of DTS. Materials and Methods: Forty-five patients (24 male and 21 female; age range, 25-77 years) with clinically suspected ONFH underwent anteroposterior radiography, DTS, and CT. Two musculoskeletal radiologists independently evaluated the presence and type of ONFH. The diagnostic performance of radiography and DTS in detecting the presence of ONFH and determining the types of ONFH were evaluated. The interobserver and intraobserver reliabilities of each imaging modality were analyzed using Cohen's kappa. Results: DTS had higher sensitivity (89.4%-100% vs. 74.5%-76.6%) and specificity (97.3%-100% vs. 78.4%-83.8%) for ONFH detection than radiography. DTS showed higher performance than radiography in identifying the subtypes of ONFH with statistical significance in one reader (type 1, 100% vs. 30.8%, p = 0.004; type II, 97.1% vs. 73.5%, p = 0.008). The interobserver agreement was excellent for DTS and moderate for radiography (kappa of 0.86 vs. 0.57, respectively). The intraobserver agreement for DTS was higher than that of radiography (kappa of 0.96 vs. 0.69, respectively). Conclusion: DTS showed higher diagnostic performance and reproducibility than radiography in detecting ONFH. DTS may be used as a first-line diagnostic modality instead of radiography for patients suspected of having ONFH.

• Molecules and Cells
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• v.26 no.5
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• pp.490-495
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• 2008

Thrombophilia and hypofibrinolysis have been implicated in the pathogenesis of osteonecrosis of the femoral head (ONFH). Tissue factor pathway inhibitor (TFPI), a multivalent protease inhibitor, is an important regulator of the tissue factor-mediated blood coagulation pathway. Mutations of the TFPI gene can increase the risk of thrombin generation and venous thrombosis. The aim of this study was to evaluate the association of TFPI gene polymorphisms with ONFH. All exons and their boundaries of the TFPI gene, including the -1,500 bp promoter region, were directly sequenced in 24 Korean individuals and four sequence variants were identified. These four polymorphisms [-51096 G > A (C-399T), -50984A > G (T-287C), + 24999A > G (Int7 -33T > C), + 37339T > A] were genotyped in 474 ONFH patients and 349 control subjects. The association of genotyped SNPs with ONFH was not found in the present study. The haplotype AAAT of TFPI was significantly associated with total, alcohol-induced, and idiopathic ONFH (p = 0.003, 0.021, and 0.007, respectively), and the haplotype GAAT was significantly associated with total and alcohol ONFH (p = 0.022 and 0.009, respectively). In addition, a new SNP + 37339 T > A in the 3'-UTR of the TFPI gene, was found in the Korean population. To date, this study is the first to show that haplotypes of the TFPI gene are associated with an increased susceptibility for ONFH. The results suggest that genetic variations in TFPI may play an important role in the pathogenesis and risk factors of ONFH.

• Hip & pelvis
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• v.35 no.3
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• pp.147-156
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• 2023

Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply. Its occurrence is more common in young and middle-aged adults and it is the main reason for performance of total hip arthroplasty in this age group. Its incidence is increasing along with increased use of glucocorticoids for management of adjuvant therapy for treatment of leukemia as well as organ transplantation and other myelogenous diseases. Current information on etiology and pathogenesis, as well as natural history, stage system, and treatments is provided in this review. A description of the Association Research Circulation Osseous (ARCO) criteria for classification of glucocorticoids-and alcohol-associated ONFH, 2019 ARCO staging system, and 2021 ARCO classification using computed tomography for the early stages of ONFH is also provided.

• IMMUNE NETWORK
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• v.22 no.3
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• pp.25.1-25.11
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• 2022

IL-34 can promote osteoclast differentiation and activation, which may contribute to steroid-induced osteonecrosis of the femoral head (ONFH). Animal model was constructed in both BALB/c and IL-34 deficient mice to detect the relative expression of inflammation cytokines. Micro-CT was utilized to reveal the internal structure. In vitro differentiated osteoclast was induced by culturing bone marrow-derived macrophages with IL-34 conditioned medium or M-CSF. The relative expression of pro-inflammation cytokines, osteoclast marker genes, and relevant pathways molecules was detected with quantitative real-time RT-PCR, ELISA, and Western blot. Up-regulated IL-34 expression could be detected in the serum of ONFH patients and femoral heads of ONFH mice. IL-34 deficient mice showed the resistance to ONFH induction with the up-regulated trabecular number, trabecular thickness, bone value fraction, and down-regulated trabecular separation. On the other hand, inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-12, IL-2, and IL-17A, showed diminished expression in IL-34 deficient ONFH induced mice. IL-34 alone or works in coordination with M-CSF to promote osteoclastogenesis and activate ERK, STAT3, and non-canonical NF-κB pathways. These data demonstrate that IL-34 can promote the differentiation of osteoclast through ERK, STAT3, and non-canonical NF-κB pathways to aggravate steroid-induced ONFH, and IL-34 can be considered as a treatment target.

• The Journal of Internal Korean Medicine
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• v.41 no.1
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• pp.88-96
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• 2020

Objectives: Osteonecrosis of the femoral head (ONFH) is caused by a circulatory disorder. If symptoms are not present, the patient's progress is observed, but if symptoms are present, non-surgical methods or total hip replacement are performed. Several case reports have described the effects of Korean Medicine treatment on ONFH, but the number of cases is still small, and few studies have used blood stasis-based herbal medicines like Hwaeo-jeon (HEJ). This study reports the effectiveness of Korean Medicine treatments, including HEJ, on a case of ONFH. Methods: A patient diagnosed with ONFH by CT and MRI was treated with Korean Medicine treatments consisting of herbal medicine including HEJ, bee venom pharmacopuncture, acupuncture, cupping, and physical therapy. The improvement of pain was assessed using a numerical rating scale. Inflammation levels were determined by blood tests conducted during hospitalization. Results: Korean Medicine treatment, including herbal medicine, resulted in good clinical improvement responses, including reduced pain, improved mobility, and reduced inflammatory levels in the blood tests. Conclusions: Korean Medicine treatments, including HEJ, may be effective for ONFH patients. Further studies are needed to determine the recovery of osteonecrosis and the improvement of post-operative aftereffects using Korean Medicine treatments, as well as the reduction of pre-operative pain.

• Journal of Life Science
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• v.18 no.4
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• pp.427-434
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• 2008

Osteonecrosis of the femoral head (ONFH) is a multifactorial disease and certain individuals are more at risk or may be predisposed to it. An altered lipid metabolism is one of the major risk factors for osteonecrosis, especially corticosteroid therapy and alcoholism. 3-hydroxy-3-methylglutaryl coenzyme A. (HMG-CoA) reductase inhibitors, stalin used as lipid-clearing agent, have been known to decrease the risk of osteonecrosis in patients receiving steroids and affect coagulation and fibrinolysis. Therefore we evaluated the association of HMG-CoA reductase gene polymorphisms and haplotypes between osteonecrosis patients and normal controls. We directly sequenced the HMG-CoA reductase gene in 24 Korean individuals, and identified five sequence variants. Four SNPs (-6933C>T, -6045T>G, +12673G>A, and +18128C>T) were selected and genotyped in 349 male ONFH patients and 300 male control subjects. The genotypes, allele frequencies, and haplotypes of the polymorphisms in the total patients as well as in the subgroup by etiology were not significantly different from those in the control group. In addition, no significant differences between each genotype of the polymorphisms and plasma lipid level could be found in the control group. These results suggest that the polymorphisms and haplotypes of HMG-CoA reductase gene are unlikely to be associated with a susceptibility to ONFH.

• Proceedings of the KOSOMBE Conference
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• v.1997 no.05
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• pp.374-378
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• 1997

Operative procedures such as core drilling with and without fibular bone grafting have been recognized as the treatment methods for osteonecrosis of femoral head(ONFH) by delaying or preventing the collapse of the femoral head. In addition, core drilling with cementation using polymethylmethacrylate (PMMA) has been proposed recently as another surgical method. However, no definite treatment modality has been found yet while operative procedures remain controversial to many clinicians In this study, a finite element method(FEM) was employed to analyze and compare various surgical procedures of ONFH to provide a biomechanical insight. This study was based upon biomechanical findings which suggest stress concentration within the femoral head may facilitate the progression of the necrosis and eventual collapse. For this purpose, five anatomically relevant hip models were constructed in three dimensions : they were (1) intact(Type I), (2) necrotic(Type II), (3) core drilled only(Type III), (4) core drilled with fibular bone graft(Type IV), and (5) core drilled with cementation(Type V). Physiologically relevant loading were simulated. Resulting stresses were calculated. Our results showed that the volumetric percentage subjected to high stress in the necrotic cancellous region was greatest in the core drilled only model(Type III), followed by the necrotic(Type II), the bone graft (Type IV), and the cemented(Type V) models. Von Mises stresses at the tip of the graft(Type IV) was found to be twice more than those of cemented core(Type V) indicating the likelihood of the implant failure. In addition, stresses within the cemented core(Type V) were more evenly distributed and relatively lower than within the fibular bone graft(Type IV). In conclusion, our biomechanical analyses have demonstrated that the bone graft method(Type IV) and the cementation method(Type V) are both superior to the core decompression method(Type III) by reducing the high stress regions within the necrotic cancellous bone. Also it was found that the core region filled with PMMA(Type V) provides far smoother transfer of physiological load without causing the concentration of malignant stresses which may lead to the failure than with the fibular bone graft(Type IV). Therefore, considering the above results along with the degree of difficulties and risk of infection involved with preparation of the fibular bone graft, the cementation method appears to be a promising surgical treatment for the early stage of osteonecrosis of the femoral head.

• Proceedings of the KOSOMBE Conference
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• v.1997 no.11
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• pp.245-248
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• 1997

Operative interventions for the management of osteonecrosis of the femoral head (ONFH) include core drilling, with or without vascularized fibular bone grafting. Nevertheless, their clinical results have not been consistently satisfactory. Recently, a new surgical procedure that incorporates cementation with polymethylmethacrylate (PMMA) after core drilling has been tried clinically. In this study, a biomechanical analysis using a finite element method(FEM) was undertaken to evaluate surgical methods and their underlying surgical parameter. Our finite element models included five types. They were (1) normal model (Type I), (2) necrotic model (Type II), (3) core decompressed model (Type III). (4) fibular bone grafted model (Type IV), and (5) cemented with PMMA model (Type V). The geometric dimensions of the femur were based on digitized CT-scan data of a normal person. Various physiological loading conditions and surgical penetration depths by the core were used as mechanical variables to study their biomechanical contributions in stress transfer within the femoral head region. In addition. the peak von Mises stress(PVMS) within the necrotic cancellous bone of the femoral head was obtained. The fibular bone grafted method and cementation method provided optimal stress transfer behaviors. Here. substantial increase in the low stress level was observed when the penetration depth was extended to 0mm and 5mm from the subchondral region. Moreover, significant decrease in PVMS due to surgery was observed in the fibular bone grafted method and the cementation method when the penetration depths were extended up to 0 and 5mm from the subchondral region. The drop in PVMS was greater during toe-off than during heel-strike (57% vs. 28% in Type IV and 49% vs. 22% in Type V). Both the vascularized fibular bone grafting method (Type IV) and the new PMMA technique (Type V) appear to be very effective in providing good stress transfer and reducing the peak Von-Mises stress within the necrotic region. Overall results show that fibular bone grafting and cementation methods are quite similar. In light of above results, the new cementation method appears to be a promising surgical alternative or the treatment of ONFH. The use of PMMA for the core can be less prone to surgical complication as opposed to preparation of fibular bone graft and can achieve more immediate fixation between the core and the surrounding region.