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An Y, Zheng L, Zhang S, Zhang H, Zhang Y, Shao H, Tong W, Chen Z, Yao H, Wen Z, Xu S, Li Y, Tian Q, Cheng L, Sun W, Qin L, Xu J. Hydrogen activates ACOD1-itaconate pathway to ameliorate steroid-associated osteonecrosis. Biomaterials 2025; 323:123428. [PMID: 40411985 DOI: 10.1016/j.biomaterials.2025.123428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 05/06/2025] [Accepted: 05/19/2025] [Indexed: 05/27/2025]
Abstract
Steroid-associated osteonecrosis (SAON) remains a challenging clinical condition as there are few effective preventive measures. This study investigates the effects of hydrogen (H2) administrated via saturated hydrogen-rich water (HRW) in mice received high dose of glucocorticoids (for inducing SAON model). Here we find that HRW treatment significantly reduces osteocyte apoptosis, improves deteriorated trabecular architecture, increases osteoblast numbers and the bone formation, while decreases osteoclast numbers and the bone resorption. Additionally, HRW-treated mice exhibit improved serum lipid profiles, including decreased levels of low-density lipoprotein (LDL), triglycerides (TG), and total cholesterol (T-CHO), as well as reduced lipid accumulation. HRW treatment also enhances blood perfusion and increases formation of type H vessels in SAON mice. We further demonstrate that HRW shifts the polarization of macrophages from M1 to M2 phenotype and suppresses inflammatory marker TNF-α. RNA sequencing data and subsequent validation reveal that HRW upregulates ACOD1 mRNA and protein levels in bone tissues. The protective effects of HRW are mimicked by supplementation with the itaconate derivative dimethyl itaconate in a dose-dependent manner, highlighting the importance of the ACOD1-itaconate pathway in the prevention of SAON by HRW. These findings indicate that HRW ameliorates SAON by modulating the ACOD1-itaconate pathway, presenting a novel avenue for the cost-effective prevention of osteonecrosis.
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Affiliation(s)
- Yuanming An
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China; The Sir Yue-Kong Pao Cancer Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Lizhen Zheng
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation (InnoHK), Chinese Academy of Sciences, Hong Kong Special Administrative Region of China
| | - Shi'an Zhang
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Haozhi Zhang
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China; The Sir Yue-Kong Pao Cancer Centre, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Disruptive Innovation Centre for Spatiotemporal Imaging, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Yuantao Zhang
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Hongwei Shao
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Wenxue Tong
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Ziyi Chen
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Hao Yao
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Zhenkang Wen
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China; Disruptive Innovation Centre for Spatiotemporal Imaging, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Shunxiang Xu
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Ye Li
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Qinyu Tian
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Liming Cheng
- Department of Orthopaedic Surgery, China-Japan Friendship Hospital, Beijing, PR China
| | - Wei Sun
- Chengdu Hip and Femoral Head Hospital, Sichuan, PR China
| | - Ling Qin
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China.
| | - Jiankun Xu
- Musculoskeletal Research Laboratory, Centre for Musculoskeletal Degeneration & Regeneration, Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chines University of Hong Kong, Hong Kong Special Administrative Region of China; Disruptive Innovation Centre for Spatiotemporal Imaging, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China.
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Yue J, Zhang Q, Guo X, Li K, Wang R, Fu H. Clinical outcomes and risk factors for failure of nano-hydroxyapatite/polyamide 66 bracing rod combined with allogeneic bone in treatment of early-stage osteonecrosis of the femoral head. INTERNATIONAL ORTHOPAEDICS 2025:10.1007/s00264-025-06548-7. [PMID: 40317313 DOI: 10.1007/s00264-025-06548-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2025] [Accepted: 04/21/2025] [Indexed: 05/07/2025]
Abstract
PURPOSE This study was performed to analyse the clinical factors associated with failure of nano-hydroxyapatite/polyamide 66 (nHA/PA66) bracing rods combined with allogeneic bone in the treatment of early-stage osteonecrosis of the femoral head (ONFH). METHODS In total, 96 patients were treated with nHA/PA66 bracing rods combined with allogeneic bone for ONFH between October 2016 and September 2020. The patients were classified according to aetiology, Association Research Circulation Osseous (ARCO) type, Japanese Investigation Committee (JIC) type, age, and body mass index(BMI). The outcome measures were the Hip Harris Score (HHS), imaging changes, and the need for total hip arthroplasty (THA) (performed in cases of clinical failure, at which point follow-up was discontinued). RESULTS All patients were included in the study, with a mean follow-up duration of 50.76 ± 17.94 months. The preoperative HHS was 79.00 ± 13.61 and that at the final follow-up was 81.73 ± 17.67(P = 0.149). The excellent and good rate improved from 43.88% preoperatively to 65.47% at the final follow-up(P = 0.000). The radiographic progression rate was 36.70% and the incidence of THA was 23.02%. Univariate analysis identified ARCO type (P = 0.000), JIC type (P = 0.000), and age (P = 0.003) as independent risk factors for postoperative failure. Postoperative multivariate analysis also confirmed ARCO type, JIC classification, and age as risk factors. CONCLUSION This technique is not recommended for patients older than 44 years or those with ARCO type 3 or JIC type C ONFH.
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Affiliation(s)
- Ju'an Yue
- Aviation General Hospital, Beijing, China
| | | | | | - Ke Li
- Shenyang Hip Protection Orthopedic Hospital, Shenyang, China.
| | | | - Hao Fu
- Aviation General Hospital, Beijing, China
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Chen T, Luo L, Li J, Li J, Lin T, Liu M, Sang H, Hong X, Pu J, Huang W. Advancements in 3D printing technologies for personalized treatment of osteonecrosis of the femoral head. Mater Today Bio 2025; 31:101531. [PMID: 40026627 PMCID: PMC11869124 DOI: 10.1016/j.mtbio.2025.101531] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/25/2025] [Accepted: 01/28/2025] [Indexed: 03/05/2025] Open
Abstract
Three-dimensional (3D) printing technology has shown significant promise in the medical field, particularly in orthopedics, prosthetics, tissue engineering, and pharmaceutical preparations. This review focuses on the innovative application of 3D printing in addressing the challenges of osteonecrosis of the femoral head (ONFH). Unlike traditional hip replacement surgery, which is often suboptimal for younger patients, 3D printing offers precise localization of necrotic areas and the ability to create personalized implants. By integrating advanced biomaterials, this technology offers a promising strategy approach for early hip-preserving treatments. Additionally, 3D-printed bone tissue engineering scaffolds can mimic the natural bone environment, promoting bone regeneration and vascularization. In the future, the potential of 3D printing extends to combining with artificial intelligence for optimizing treatment plans, developing materials with enhanced bioactivity and compatibility, and translating these innovations from the laboratory to clinical practice. This review demonstrates how 3D printing technology uniquely addresses critical challenges in ONFH treatment, including insufficient vascularization, poor mechanical stability, and limited long-term success of conventional therapies. By introducing gradient porous scaffolds, bioactive material coatings, and AI-assisted design, this work outlines novel strategies to improve bone regeneration and personalized hip-preserving interventions. These advancements not only enhance treatment efficacy but also pave the way for translating laboratory findings into clinical applications.
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Affiliation(s)
- Tingting Chen
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian , 350108, China
| | - Lincong Luo
- Yue Bei People's Hospital Postdoctoral Innovation Practice Base, Southern Medical University, Guangzhou, 510515, China
| | - Jiaying Li
- Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong , 510515, China
| | - Jiamin Li
- School of Basic Medical Sciences, Guangdong Medical University, Dongguan, 523808, China
| | - Tao Lin
- Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong , 510515, China
| | - Mingrui Liu
- School of Basic Medicine, Dali University, Dali, Yunnan, 671003, China
| | - Hang Sang
- Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong , 510515, China
| | - Xinyu Hong
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian , 350108, China
| | - Jiahao Pu
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian , 350108, China
| | - Wenhua Huang
- School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian , 350108, China
- Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong , 510515, China
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Guo S, Deng W, Xiao W, Zhang Y, Yang D, Zhou Y. Short-term outcomes of AVN CAGE implantation for early-stage osteonecrosis of the femoral head. Hip Int 2025; 35:181-189. [PMID: 39648974 DOI: 10.1177/11207000241304362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2024]
Abstract
PURPOSE Considering the low survival rate for the numerous hip-preserving procedures developed for treating early-stage osteonecrosis of the femoral head (ONFH), this study aimed to evaluate short-term clinical outcomes following avascular necrosis (AVN) CAGE implantation. METHODS 58 hips with early-stage ONFH (44 with Association Research Circulation Osseous [ARCO] stage 2 and 14 with stage 3A) treated with the AVN CAGE between August 2018 and December 2021 were included. The survival rates were analysed using radiographic progression and conversion to subsequent total hip arthroplasty (THA) as endpoints. RESULTS The mean follow-up period was 22.2 ± 8.2 months. 11 hips progressed to ARCO stage 3B/4, and 6 underwent THA. The estimated 2-year radiographic survival rates were 89.1% and 59.0% for patients with ARCO stages 2 and 3A, respectively. The estimated 2-year radiographic survival rates were 92.9% and 76.3% for Japanese Investigation Committee type B/C1 and C2, respectively. The overall estimated 2-year THA-free survival rate was 88.9%. Advanced disease stage and a large necrotic area were independent risk factors for radiographic progression. CONCLUSIONS AVN CAGE combined with standard core decompression was a promising hip-preserving option for patients with no signs of collapse, small necrotic areas, or medially located necrotic locations.
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Affiliation(s)
- Shaoyi Guo
- Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Wang Deng
- Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Wenzhou Xiao
- Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Yunfeng Zhang
- Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Dejin Yang
- Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
| | - Yixin Zhou
- Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China
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Lu S, Lin T, Han L, Li Z, He M, Wei Q. Location or size? A finite element analysis study of necrotic lesion impact on femoral head collapse. J Orthop Surg Res 2025; 20:48. [PMID: 39815308 PMCID: PMC11734371 DOI: 10.1186/s13018-025-05453-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 01/02/2025] [Indexed: 01/18/2025] Open
Abstract
BACKGROUND The location and size of necrotic lesions are important factors for collapse, The preserved angles (PAs) are divided into anterior preserved angle (APA) and lateral preserved angle (LPA), which could accurately measure the location of necrosis lesion. We used them to evaluate the effect of the location and size of necrotic lesions on collapse by finite element analysis, to offer a framework for evaluating the prognosis of osteonecrosis of the femoral head (ONFH) in clinical settings. METHODS 3 left hip models were constructed based on CT data. Within each hip model, three necrosis lesion models were modeled, with necrotic tissue volumes of 30%, 50%, and 70% repectively. The ONFH models with LPA of 45.5°, 50.5°, 55.5°, 60.5°, 65.5°, 70.5°, and 75.5° when APA was 60.5°, and ONFH models with APAs of 45.5°, 50.5°, 55.5°, 60.5°, 65.5°, 70.5°, and 75.5° when LPA was 60.5° were Constructed. The maximum von Mises stess of the femoral head and necrotic lesion, as well as the femoral head displacement, were calculated to evaluate the biomechanical effects of these models. RESULTS (1) In models with the same necrotic volume, when APA was 60.5°, the indexes of the LPA < 60.5° models were significantly higher than those of the LPA ≥ 60.5° models (P < 0.05); the differences of the indexes among the LPA ≥ 60.5° models were not statistically significant (P > 0.05). (2) When LPA was 60.5°, the indexes of models with APA < 60.5 ° and APA ≥ 60.5 ° show the same trend as the former. (3) In the models with the same PAs, there was no statistically significant difference in the indexes (P > 0.05). CONCLUSION The location of the necrotic lesion exerts a greater impact on femoral head collapse compared with the size of the lesion. The location of the necrosis may deserve more consideration when assessing the risk of collapse in patients with early onset ONFH.
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Affiliation(s)
- Shun Lu
- Guangzhou University of Chinese Medicine, Guangzhou, 510405, P. R. China
| | - Tianye Lin
- The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510378, P. R. China
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, 510378, P. R. China
| | - Longfei Han
- Guangzhou University of Chinese Medicine, Guangzhou, 510405, P. R. China
| | - Ziqi Li
- The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510378, P. R. China
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, 510378, P. R. China
| | - Mingcong He
- The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510378, P. R. China.
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, 510378, P. R. China.
| | - Qiushi Wei
- The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510378, P. R. China.
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, 510378, P. R. China.
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Jia D, Zhang Y, Li H, Guo C, Wu Y, Shi X, Yang L, Mo J, Liu X, Xu Y. Predicting steroid-induced osteonecrosis of the femoral head: role of lipid metabolism biomarkers and radiomics in young and middle-aged adults. J Orthop Surg Res 2024; 19:749. [PMID: 39533346 PMCID: PMC11558989 DOI: 10.1186/s13018-024-05245-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Femoral head necrosis is a common orthopedic disease that results in significant physical disability in patients. Early prediction and diagnosis of steroid-induced osteonecrosis of the femoral head (SONFH) are crucial for the prevention and treatment of this condition. METHODS In this study, initial CT images and clinical data of patients with SONFH, admitted from January 2019 to December 2022, were collected. Patients were grouped as follows: (1) those diagnosed with SONFH at the initial diagnosis (control group), and (2) those with high-risk factors but no symptoms at first diagnosis, who developed SONFH two years later (experimental group). CT imaging histological features, clinical characteristics, and transcriptome screening for differentially expressed genes, pathway enrichment, and immune infiltration analyses were performed. RESULTS Significant differences were found in triglyceride (TG) levels between the training and validation groups. Age, sex, alkaline phosphatase (ALP), and hemoglobin levels differed between the training and internal validation groups, while HDL and red blood cell counts varied between the training and external validation groups. Univariate analysis showed that age, TG, HDL, and Radiomics scores influenced SONFH, while multivariate analysis revealed TG, HDL, and Radiomics scores were closely related to SONFH. Transcriptomic analysis showed associations with sphingolipid and adipocyte signaling pathways, along with immune cell involvement, linking SONFH to lipid metabolism and atherosclerosis. CONCLUSIONS These findings indicate a significant association between steroid-induced osteonecrosis of the femoral head and age, with TG and HDL serving as indicators of lipid metabolism closely correlated with the occurrence of SONFH. Radiomics scores were also found to correlate with SONFH occurrence, supported by transcriptomic and CT imaging findings. However, this study has limitations, including its retrospective design and a relatively limited sample size, which may impact the generalizability of the results. Further prospective studies with larger, more diverse populations are needed to validate and enhance the predictive model.
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Affiliation(s)
- Daqi Jia
- Department of Pathology, Affiliated Banan Hospital of Chongqing Medical University, Longzhouwan Street, Yunan District, Chongqing, 401320, China
| | - Yue Zhang
- Kunming Medical University, No. 1168, Chunrong West Road, Yuhua Street, Chenggong District, Kunming, 650500, China
- Department of Orthopaedics, 920th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, 212 Daguan Road, Xishan District, Kunming, 650032, China
| | - Huaqiang Li
- Department of Pathology, Affiliated Banan Hospital of Chongqing Medical University, Longzhouwan Street, Yunan District, Chongqing, 401320, China
| | - Chunfang Guo
- Department of Pathology, Affiliated Banan Hospital of Chongqing Medical University, Longzhouwan Street, Yunan District, Chongqing, 401320, China
| | - Yipeng Wu
- Department of Orthopaedics, 920th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, 212 Daguan Road, Xishan District, Kunming, 650032, China
| | - Xiangwen Shi
- Kunming Medical University, No. 1168, Chunrong West Road, Yuhua Street, Chenggong District, Kunming, 650500, China
- Department of Orthopaedics, 920th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, 212 Daguan Road, Xishan District, Kunming, 650032, China
| | - Li Yang
- Department of Pathology, Affiliated Banan Hospital of Chongqing Medical University, Longzhouwan Street, Yunan District, Chongqing, 401320, China
| | - Jieyu Mo
- Department of Pathology, Affiliated Banan Hospital of Chongqing Medical University, Longzhouwan Street, Yunan District, Chongqing, 401320, China
| | - Xia Liu
- Department of Pathology, Affiliated Banan Hospital of Chongqing Medical University, Longzhouwan Street, Yunan District, Chongqing, 401320, China
| | - Yongqing Xu
- Department of Orthopaedics, 920th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army, 212 Daguan Road, Xishan District, Kunming, 650032, China.
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Sun Z, Wang J, Ji Z, Ma J, Chen Y, Jiao G. Ortho-silicic Acid Prevents Glucocorticoid-Induced Femoral Head Necrosis by Promoting Akt Phosphorylation to Inhibit Endoplasmic Reticulum Stress-Mediated Apoptosis and Enhance Angiogenesis and Osteogenesis. Biol Trace Elem Res 2024; 202:4988-4999. [PMID: 38177717 DOI: 10.1007/s12011-023-04048-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 12/27/2023] [Indexed: 01/06/2024]
Abstract
Glucocorticoid-induced osteonecrosis of the femoral head (SONFH) is the most prevalent form of secondary osteonecrosis affecting the femoral head. Glucocorticoids can cause damage to both vascular endothelial cells and osteoblasts. Previous studies have demonstrated that silicon can improve the resistance of vascular endothelial cells to oxidative stress and positively impact bone health. However, the impact of silicon on SONFH has yet to be investigated. We examined the influence of ortho-silicic acid (OSA, Si(OH)4) on the apoptosis and proliferation of vascular endothelial cells after glucocorticoid induction. Additionally, we evaluated the expression of apoptosis-related genes such as cleaved-caspase-3, Bcl-2 and Bax. The impact of glucocorticoids and OSA on the function of vascular endothelial cells was evaluated through wound healing, transwell and angiogenesis assays. Osteogenic function was subsequently evaluated through alizarin red staining, alkaline phosphatase staining and expression levels of osteogenic genes like RUNX2 and ALP. Moreover, we investigated the potential role of OSA in vivo using the SONFH animal model. At concentrations below 100 μM, OSA exhibits no toxicity on vascular endothelial cells and effectively reverses glucocorticoid-induced apoptosis in these cells. OSA increases the resilience of vascular endothelial cells against oxidative stress and enhances osteoblast differentiation. Our study revealed that glucocorticoids activate endoplasmic reticulum stress, a process that mediates the apoptosis of vascular endothelial cells. OSA ameliorated the endoplasmic reticulum stress associated with glucocorticoids through the increased expression of p-Akt levels. In vivo, OSA treatment effectively improved SONFH by enhancing vascular endothelial cell function and promoting osteogenic differentiation. OSA counteracted the adverse effects of glucocorticoids both in vitro and in vivo, demonstrating a beneficial therapeutic effect on SONFH.
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Affiliation(s)
- Zhenqian Sun
- Department of Orthopaedics, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan, Shandong, 250012, People's Republic of China
- Shandong University, Wenhuaxi Road 107, Jinan, Shandong Province, People's Republic of China
| | - Jian Wang
- Department of Orthopaedics, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan, Shandong, 250012, People's Republic of China
- Shandong University, Wenhuaxi Road 107, Jinan, Shandong Province, People's Republic of China
| | - Zhongjie Ji
- Department of Orthopaedics, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan, Shandong, 250012, People's Republic of China
- Shandong University, Wenhuaxi Road 107, Jinan, Shandong Province, People's Republic of China
| | - Jinlong Ma
- Department of Orthopaedics, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan, Shandong, 250012, People's Republic of China
- Shandong University, Wenhuaxi Road 107, Jinan, Shandong Province, People's Republic of China
| | - Yunzhen Chen
- Department of Orthopaedics, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan, Shandong, 250012, People's Republic of China.
| | - Guangjun Jiao
- Department of Orthopaedics, Qilu Hospital of Shandong University, Wenhuaxi Road 107, Jinan, Shandong, 250012, People's Republic of China.
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Duan P, Yu YL, Cheng YN, Nie MH, Yang Q, Xia LH, Ji YX, Pan ZY. Exosomal miR-1a-3p derived from glucocorticoid-stimulated M1 macrophages promotes the adipogenic differentiation of BMSCs in glucocorticoid-associated osteonecrosis of the femoral head by targeting Cebpz. J Nanobiotechnology 2024; 22:648. [PMID: 39438865 PMCID: PMC11494760 DOI: 10.1186/s12951-024-02923-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2024] [Accepted: 10/10/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND By interacting with bone marrow mesenchymal stem cells (BMSCs) and regulating their function through exosomes, bone macrophages play crucial roles in various bone-related diseases. Research has highlighted a notable increase in the number of M1 macrophages in glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Nevertheless, the intricate crosstalk between M1 macrophages and BMSCs in the glucocorticoid-stimulated environment has not been fully elucidated, and the underlying regulatory mechanisms involved in the occurrence of GA-ONFH remain unclear. METHODS We employed in vivo mouse models and clinical samples from GA-ONFH patients to investigate the interactions between M1 macrophages and BMSCs. Immunofluorescence staining was used to assess the colocalization of M1 macrophages and BMSCs. Flow cytometry and transcriptomic analysis were performed to evaluate the impact of exosomes derived from normal (n-M1) and glucocorticoid-stimulated M1 macrophages (GC-M1) on BMSC differentiation. Additionally, miR-1a-3p expression was altered in vitro and in vivo to assess its role in regulating adipogenic differentiation. RESULTS In vivo, the colocalization of M1 macrophages and BMSCs was observed, and an increase in M1 macrophage numbers and a decrease in bone repair capabilities were further confirmed in both GA-ONFH patients and mouse models. Both n-M1 and GC-M1 were identified as contributors to the inhibition of osteogenic differentiation in BMSCs to a certain extent via exosome secretion. More importantly, exosomes derived from GC-M1 macrophages exhibited a heightened capacity to regulate the adipogenic differentiation of BMSCs, which was mediated by miR-1a-3p. In vivo and in vitro, miR-1a-3p promoted the adipogenic differentiation of BMSCs by targeting Cebpz and played an important role in the onset and progression of GA-ONFH. CONCLUSION We demonstrated that exosomes derived from GC-M1 macrophages disrupt the balance between osteogenic and adipogenic differentiation in BMSCs, contributing to the pathogenesis of GA-ONFH. Inhibiting miR-1a-3p expression, both in vitro and in vivo, significantly mitigates the preferential adipogenic differentiation of BMSCs, thus slowing the progression of GA-ONFH. These findings provide new insights into the regulatory mechanisms underlying GA-ONFH and highlight potential therapeutic targets for intervention.
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Affiliation(s)
- Ping Duan
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
- TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Yong-Le Yu
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Yan-Nan Cheng
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Meng-Han Nie
- TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China
| | - Qing Yang
- TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China
| | - Liang-Hui Xia
- TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China
| | - Yan-Xiao Ji
- TaiKang Medical School (School of Basic Medical Sciences), Wuhan University, Wuhan, 430071, China.
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
- Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China.
| | - Zhen-Yu Pan
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
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Fang GZ, Lin J, Cao LH, Liu TS, Ma YH, Yang L. Changes in postoperative depression and anxiety and their relationship with recovery from femoral head necrosis: A longitudinal study. World J Psychiatry 2024; 14:1506-1512. [DOI: 10.5498/wjp.v14.i10.1506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 08/23/2024] [Accepted: 08/26/2024] [Indexed: 10/17/2024] Open
Abstract
BACKGROUND Femoral head necrosis (FHN) can significantly affect patients' psychological well-being and functional outcomes. However, the long-term relationship between postoperative depression, anxiety, and functional recovery in patients with FHN remains unclear.
AIM To investigate the dynamic changes in postoperative depression and anxiety and their relationship with functional recovery in patients with FHN for 3 years.
METHODS Ninety-three patients with FHN who underwent surgical treatment in March 2020 to 2023 were enrolled in this longitudinal study. Depression and anxiety status were assessed using the hospital anxiety and depression scale (HADS) at baseline, 6 months, 1, 2, and 3 years postoperatively. Functional recovery was evaluated using the Harris hip score (HHS). The dynamic changes in HADS and HHS were analyzed using repeated measures ANOVA; the relationship between depression/anxiety status and functional recovery was examined using Pearson’s correlation analysis.
RESULTS The mean HADS-depression (HADS-D) and HADS-anxiety (HADS-A) scores significantly improved over time (P < 0.001). The prevalence of depression and anxiety decreased from 36.6% and 41.9% at baseline to 10.8% and 12.9%, respectively, at 3 years postoperatively. The mean HHS increased significantly from 52.3 ± 10.5 at baseline to 88.1 ± 7.2 at 3 years postoperatively (P < 0.001). Significant negative correlations were found between HADS-D/HADS-A scores and HHS at all time points (P < 0.05).
CONCLUSION The severity of depression and anxiety negatively correlated with functional recovery, highlighting the importance of psychological interventions in the management of patients with FHN.
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Affiliation(s)
- Guo-Zheng Fang
- Department of Orthopedics, Shanghai Baoshan Luodian Hospital, Shanghai 201908, China
| | - Jie Lin
- Department of Orthopedics, Shanghai Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200082, China
| | - Lie-Hu Cao
- Department of Orthopedics, Shanghai Baoshan Luodian Hospital, Shanghai 201908, China
| | - Tong-Sheng Liu
- Department of Orthopedics, Shanghai Baoshan Luodian Hospital, Shanghai 201908, China
| | - Yu-Hong Ma
- Department of Orthopedics, Shanghai Baoshan Luodian Hospital, Shanghai 201908, China
| | - Lu Yang
- Department of Orthopedics, Shanghai Baoshan Luodian Hospital, Shanghai 201908, China
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Huang J, Ma T, Wang C, Wang Z, Wang X, Hua B, Jiang C, Yan Z. SOST/Sclerostin impairs the osteogenesis and angiogesis in glucocorticoid-associated osteonecrosis of femoral head. Mol Med 2024; 30:167. [PMID: 39342093 PMCID: PMC11439244 DOI: 10.1186/s10020-024-00933-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2023] [Accepted: 09/09/2024] [Indexed: 10/01/2024] Open
Abstract
BACKGROUND Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a progressive bone disorder which frequently results in femoral head collapse and hip joint dysfunction. Sclerostin (SOST) is principally secreted by osteocytes in bone and plays an important role in bone homeostasis and homeostasis of skeletal integrity. Our previous study reported that short-term use of glucocorticoid increased serum sclerostin levels. Here this study is aimed to identify whether sclerostin played an essential role in the occurrence and development of GA-ONFH. METHODS Glucocorticoid-induced osteonecrosis of femoral head (ARCO stage II) samples were collected and sclerostin staining was conducted. Osteocyte cell line Ocy454, MC3T3-E1 and endothelial cells was used. MC3T3-E1 or endothelial cells were co-cultured with Ocy454 or SOST-silencing Ocy454 in presence of dexamethasone to mimic the crosstalk of various cells in the bone niche. GA-ONFH rat model and SOST knockout model was built to better understand the phenomenon in vivo. RESULTS Sclerostin was highly concentrated in osteonecrosis patient sample in the necrotic area. Co-culture with osteocytes aggravated the inhibition of dexamethasone on MC3T3-E1 and endothelial cells. Sclerostin derived from osteocytes impaired osteogenesis and angiogenesis via inhibiting the Wnt pathway. In GA-ONFH rat model, SOST knockout ameliorated the incidence of osteonecrosis and improved bone metabolism compared with the wild type group through histological, immunohistochemical and bone metabolic analyses. CONCLUSION Sclerostin contribute to pathologic process of GA-ONFH by impairing osteogenesis and angiogenesis.
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Affiliation(s)
- Junming Huang
- Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China
| | - Tianle Ma
- Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China
| | - Chenzhong Wang
- Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China
| | - Zhe Wang
- Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China
| | - Xinyuan Wang
- Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China
| | - Bingxuan Hua
- Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China
| | - Chang Jiang
- Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China.
| | - Zuoqin Yan
- Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Xuhui District, Shanghai, 200032, China.
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Kuriyama Y, Tanaka H, Baba K, Kanabuchi R, Mori Y, Aizawa T. Acetabular coverage exerts minimal influence on femoral head collapse and the necessity for surgical intervention in patients with osteonecrosis of femoral head. INTERNATIONAL ORTHOPAEDICS 2024; 48:2331-2337. [PMID: 38898160 PMCID: PMC11347479 DOI: 10.1007/s00264-024-06238-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 06/11/2024] [Indexed: 06/21/2024]
Abstract
PURPOSE The acetabular coverage in osteonecrosis of the femoral head (ONFH) affects the need for surgical intervention, and the collapse of the femoral head remains unclear. This study aimed to evaluate the relation between the acetabular coverage and the need for surgical treatment and femoral head collapse. METHODS The study included 158 patients with 252 hips with glucocorticoid administration and idiopathic ONHF without osteoarthritis changes. The mean age at the first visit was 45.2 years, and the mean follow-up period was 92.2 months. All ONFH hips were subsequently divided into two groups: those needing surgical intervention and those without surgery. Additionally, it divided 167 initially non-collapsed hips into those that either later collapsed or not. Radiographic parameters with the centre-edge angle, acetabular roof obliquity, sharp angle, and necrotic location, following the guidelines of the Japanese Investigation Committee, were evaluated. RESULTS There were no significant differences in radiographic parameters between the 106 hips that underwent surgery and the 146 hips without surgery. Among the 167 hips without initial collapse, 91 eventually collapsed while 76 did not; their radiographic findings have no significant differences. The necrotic locations were significantly larger in hips requiring surgical intervention or femoral head collapse. Furthermore, 21.8% (55 out of 252 hips) had acetabular dysplasia, which did not significantly correlate with the necessity for surgical treatment or the incidence of femoral head collapse. CONCLUSIONS Acetabular coverage has little effect on the necessity for surgical treatment and femoral head collapse in ONFH patients over a long-term follow-up.
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Affiliation(s)
- Yasuaki Kuriyama
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Hidetatsu Tanaka
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
| | - Kazuyoshi Baba
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Ryuichi Kanabuchi
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Yu Mori
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Toshimi Aizawa
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
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12
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Zhang C, Xiong B, Wang J, Li Y, Xie B, Liu D, Zhang G, Chen W, He H. Factors influencing the survival status of the hip joint in post-collapse femoral head necrosis. J Orthop Surg Res 2024; 19:472. [PMID: 39127688 DOI: 10.1186/s13018-024-04964-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 07/29/2024] [Indexed: 08/12/2024] Open
Abstract
BACKGROUND Despite hip function typically deteriorating in the post-collapse stage of osteonecrosis of the femoral head (ONFH), some patients can still demonstrate long-term favorable hip function, a state termed "survival with collapse". This study aims to identify the characteristics of patients suitable for "survival with collapse" in cases of ONFH. METHODS This cross-sectional study included 65 patients (87 hips) diagnosed with post-collapse ONFH for ≥ 3 years (average 9.1 years, range 3-23 years). Hip function was assessed using the Harris Hip Score (HHS). Demographic, clinical, and radiographic data were compared between the favorable group (HHS > 80) and the poor group (HHS ≤ 80). Independent protective factors for hip function were identified by multivariate analysis and receiver operating characteristic (ROC) curve analysis was further applied to evaluate these factors' diagnostic efficacy. RESULTS The favorable and poor groups included 46 and 41 hips, respectively. Significant differences were found in body mass index (BMI), Association Research Circulation Osseous (ARCO) stage, collapse degree, Japanese Investigation Committee (JIC) classification, necrotic size, and hip subluxation between the two groups (p < 0.05). Multivariate logistic regression identified collapse < 3 mm(OR:14.49, 95%CI: 3.52-59.68, p < 0.001), JIC types B (OR: 11.08, 95% CI: 1.07-115.12, p < 0.05) and C1(OR: 5.18, 95% CI: 1.47-18.20, p < 0.05) as independent protective factors for hip function, while BMI (OR: 0.76, 95% CI: 0.59-0.97, p = 0.029) was an independent risk factor. ROC curve analysis demonstrated that both collapse degree (AUC = 0.798, sensitivity = 91.3%, specificity = 68.3%, p < 0.0001) and JIC classification (AUC = 0.787, sensitivity = 80.4%, specificity = 73.2%, p < 0.0001) had satisfactory diagnostic value for hip function. Combining JIC classification and collapse degree (AUC = 0.868, sensitivity = 76.1%, specificity = 85.4%, p < 0.0001) significantly enhanced diagnostic efficacy compared to using either alone (p < 0.05). CONCLUSION In ONFH, femoral head collapse does not necessarily determine a poor prognosis. Patients with mild collapse (< 3 mm) and preserved anterolateral wall are more likely to retain satisfactory hip function, making them candidates for "survival with collapse."
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Affiliation(s)
- Cheng Zhang
- Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, No.6 Wangjing Zhonghuannan Road, Chaoyang District, Beijing, 100102, China
| | - Binglang Xiong
- Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, No.6 Wangjing Zhonghuannan Road, Chaoyang District, Beijing, 100102, China
| | - Junyu Wang
- Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, No.6 Wangjing Zhonghuannan Road, Chaoyang District, Beijing, 100102, China
| | - Yan Li
- Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, No.6 Wangjing Zhonghuannan Road, Chaoyang District, Beijing, 100102, China
| | - Bin Xie
- Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, No.6 Wangjing Zhonghuannan Road, Chaoyang District, Beijing, 100102, China
| | - Daobing Liu
- Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, No.6 Wangjing Zhonghuannan Road, Chaoyang District, Beijing, 100102, China
| | - Guangyi Zhang
- Beijing University of Chinese Medicine, No.11 North Third Ring Road East, Chaoyang District, Beijing, 100029, China
| | - Weiheng Chen
- The Third Affiliated Hospital of Beijing University of Chinese Medicine, No.51 Xiaoguan Street, outside Andingmen, Chaoyang District, Beijing, 100029, China
| | - Haijun He
- Department of Orthopedics, Wangjing Hospital of China Academy of Chinese Medical Sciences, No.6 Wangjing Zhonghuannan Road, Chaoyang District, Beijing, 100102, China.
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Wang Y, Sun D, Zhang J, Kong Y, Morelli JN, Wen D, Wu G, Li X. Multi-sequence MRI-based radiomics: An objective method to diagnose early-stage osteonecrosis of the femoral head. Eur J Radiol 2024; 177:111563. [PMID: 38897051 DOI: 10.1016/j.ejrad.2024.111563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 06/03/2024] [Accepted: 06/10/2024] [Indexed: 06/21/2024]
Abstract
OBJECTIVES This study investigated the use of radiomics for diagnosing early-stage osteonecrosis of the femoral head (ONFH) by extracting features from multiple MRI sequences and constructing predictive models. MATERIALS AND METHODS We conducted a retrospective review, collected MR images of early-stage ONFH (102 from institution A and 20 from institution B) and healthy femoral heads (102 from institution A and 20 from institution B) from two institutions. We extracted radiomics features, handled batch effects using Combat, and normalized features using z-score. We employed the Least absolute shrinkage and selection operator (LASSO) algorithm, along with Max-Relevance and Min-Redundancy (mRMR), to select optimal features for constructing radiomics models based on single, double, and multi-sequence MRI data. We evaluated performance using receiver operating characteristic (ROC) and precision-recall (PR) curves, and compared area under curve of ROC (AUC-ROC) values with the DeLong test. Additionally, we studied the diagnostic performance of the multi-sequence radiomics model and radiologists, compared the diagnostic outcomes of the model and radiologists using the Fisher exact test. RESULTS We studied 122 early-stage ONFH and 122 normal femoral heads. The multi-sequence model exhibited the best diagnostic performance among all models (AUC-ROC, PR-AUC for training set: 0.96, 0.961; validation set: 0.96, 0.97; test set: 0.94, 0.94), and it outperformed three resident radiologists on the external testing group with an accuracy of 87.5 %, sensitivity of 85.00 %, and specificity of 90.00 % (p < 0.01), highlighting the robustness of our findings. CONCLUSIONS Our study underscored the novelty of the multi-sequence radiomics model in diagnosing early-stage ONFH. By leveraging features extracted from multiple imaging sequences, this approach demonstrated high efficacy, indicating its potential to advance early diagnosis for ONFH. These findings provided important guidance for enhancing early diagnosis of ONFH through radiomics methods, offering new avenues and possibilities for clinical practice and patient care.
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Affiliation(s)
- Yi Wang
- The Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan 430030, Hubei Province, People's Republic of China
| | - Dong Sun
- The Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan 430030, Hubei Province, People's Republic of China
| | - Jing Zhang
- The Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan 430030, Hubei Province, People's Republic of China
| | - Yuefeng Kong
- Radiology Department, Wuhan Fourth Hospital, No. 473 Hanzheng Street, Wuhan 430030, Hubei Province, People's Republic of China
| | - John N Morelli
- The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Donglin Wen
- The Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan 430030, Hubei Province, People's Republic of China
| | - Gang Wu
- The Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan 430030, Hubei Province, People's Republic of China.
| | - Xiaoming Li
- The Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan 430030, Hubei Province, People's Republic of China.
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Li S, Huang C, Wang W, Chen S, Deng B, Yin L, Amu Y, Ye L, Jing D, Song B, Xie Q, Liao D. Subtrochanteric fracture after core decompression for osteonecrosis of the femoral head: a case report and literature review. BMC Musculoskelet Disord 2024; 25:420. [PMID: 38811923 PMCID: PMC11134917 DOI: 10.1186/s12891-024-07536-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 05/23/2024] [Indexed: 05/31/2024] Open
Abstract
BACKGROUND Osteonecrosis of the femoral head (ONFH) is a common clinical disease. Improper treatment can lead to femoral head collapse and hip joint dysfunction. Core decompression is particularly important for early ONFH. However, subtrochanteric fractures after core decompression cause some clinical problems. CASE PRESENTATION This article describes a 34-year-old male patient with early ONFH. After core decompression, he suffered a subtrochanteric fracture of the femur while bearing weight on the affected limb when going up stairs. He was subsequently treated with open reduction and intramedullary nail fixation. CONCLUSION When core decompression is used to treat ONFH, the location or size of the drill hole, whether a tantalum rod or bone is inserted, and partial weight-bearing of the affected limb may directly affect whether a fracture occurs after surgery. It is hoped that this case report can provide a reference for clinical orthopedic surgeons in the treatment of early ONFH.
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Affiliation(s)
- Shihong Li
- The General Hospital of Western Theater Command, Chengdu, China
| | - Chen Huang
- The General Hospital of Western Theater Command, Chengdu, China
| | - Wei Wang
- The General Hospital of Western Theater Command, Chengdu, China
| | - Song Chen
- The General Hospital of Western Theater Command, Chengdu, China
| | - Bing Deng
- The General Hospital of Western Theater Command, Chengdu, China
| | - Li Yin
- The General Hospital of Western Theater Command, Chengdu, China
| | - Yida Amu
- The General Hospital of Western Theater Command, Chengdu, China
| | - Lijuan Ye
- The General Hospital of Western Theater Command, Chengdu, China
| | - Dan Jing
- The General Hospital of Western Theater Command, Chengdu, China
| | - Benjing Song
- The General Hospital of Western Theater Command, Chengdu, China
| | - Qingyun Xie
- The General Hospital of Western Theater Command, Chengdu, China.
| | - Dongfa Liao
- The General Hospital of Western Theater Command, Chengdu, China.
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15
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Liu W, Yue J, Guo X, Wang R, Fu H. Epidemiological investigation and diagnostic analysis of osteonecrosis of the femoral head in three northeastern provinces of China. J Orthop Surg Res 2024; 19:292. [PMID: 38735955 PMCID: PMC11089743 DOI: 10.1186/s13018-024-04768-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2024] [Accepted: 04/30/2024] [Indexed: 05/14/2024] Open
Abstract
BACKGROUND In this retrospective case investigation, we analysed the data of patients with osteonecrosis of the femoral head (ONFH) to reveal demographic and clinical diagnostic features of ONFH in three northeastern provinces of China and provide a reference for its prevention, diagnosis, and treatment. METHODS We collected data from patients in Beijing Orthopaedic Hospital of Liaoning, focusing on the aetiology and diagnosis of ONFH. Medical records and self-designed questionnaires were used to collect information for statistical analysis, including age, aetiology, reason for glucocorticoid use, hospital level at first visit, and diagnosis. RESULTS In total, 906 patients with complete medical records were included in the analysis. The mean patient age was 47.65 ± 12.12 years. The peak age distribution was in the 40s for men and the 50s for women. Among the total cohort, 72 patients (7.95%; 40 men and 32 women) had traumatic ONFH, 198 (21.85%; 131 men and 67 women) had steroid-induced ONFH, 230 (25.39%; 121 men and 109 women) had idiopathic ONFH, and 406 (44.81%; 397 men and 9 women) had alcohol-induced ONFH. Six hundred and twenty patients were diagnosed with ONFH at the first visit, while 286 patients were misdiagnosed, with a diagnosis rate of 68.43%. The diagnosis rate at the first visit in tertiary hospitals was 76.14%. The diagnosis rate at the first visit in second-class hospitals was 52.07%.ONFH was most likely to be misdiagnosed as lumbar disc herniation. CONCLUSIONS Most patients with ONFH in three northeastern provinces of China were middle-aged, male, and had alcohol-induced ONFH. The misdiagnosis rate of ONFH at the first visit was very high, especially for misdiagnosis of lumbar disc herniation, indicating that the diagnosis of ONFH requires further improvement.
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Affiliation(s)
- Wangyan Liu
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Ju'an Yue
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China.
| | - Xiaozhong Guo
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Randong Wang
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Hao Fu
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
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16
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Akçaalan S, Kengil MC, Çağlar C, Uğurlu M. Is there still an indication for the Birmingham Hip Resurfacing in femoral head osteonecrosis? INTERNATIONAL ORTHOPAEDICS 2024; 48:1157-1163. [PMID: 38165447 DOI: 10.1007/s00264-023-06070-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 12/11/2023] [Indexed: 01/03/2024]
Abstract
PURPOSE Osteonecrosis of the femoral head (ONFH) is a progressive hip disease. Hip resurfacing arthroplasty (HRA) is a preferred surgical procedure among hip arthroplasty performed in young patients. The aim of this study is to show the long-term clinical and radiological results of HRA procedures performed for patients suffering from ONFH. METHODS Forty-five patients who underwent hip resurfacing with the diagnosis of femoral head osteonecrosis were included in the study. The Harris Hip Score (HHS) was used for clinical scoring of the patients. The blood chromium, cobalt, white blood cell (WBC) count, and CRP levels of patients were checked. Ultrasonography (USG) was performed for all patients at mid-term control checked for pseudo-tumours. For the radiological evaluation, acetabular inclination, stem shaft angle, prothesis-to-neck ratio, osteolysis zones, and heterotopic ossification were used. RESULTS The mean age of the patients was 46.6 ± 9.3 years, and the mean follow-up period was 11.83 ± 2.9 years. The mean HHS was 90.3 ± 12.8 for final follow-up. The mean WBC value was 8.2 109/L, mean CRP value was 6.3 mg/L, mean chromium value was 4.9 µg/L, and mean cobalt value was 1.8 µg/L. Inclination changing 0.2°(p = 0.788), stem shaft angle changing 0.7°(p = 0.424), and neck-to-prosthesis ratio changing 0.01°(p = 0.075). No pseudo-tumours were detected in any patients in USG examination. CONCLUSION HRA provides long-term implant survival and excellent clinical outcomes for end-stage ONFH patients with low complication rates.
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Affiliation(s)
- Serhat Akçaalan
- Orthopedics and Traumatology Department, Ankara City Hospital, Ankara, Turkey.
| | - Mehmet Can Kengil
- Orthopedics and Traumatology Department, Ankara City Hospital, Ankara, Turkey
| | - Ceyhun Çağlar
- Orthopedics and Traumatology Department, Ankara Yıldırım Beyazıt University, Ankara, Turkey
| | - Mahmut Uğurlu
- Orthopedics and Traumatology Department, Ankara Yıldırım Beyazıt University, Ankara, Turkey
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17
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Gao Y, You Y, Zhang P, Yu Y, Xu Z, Wei H, Liu Z, Yu R, Jin G, Wang H, Zhang S, Li Y, Li W. Cortistatin prevents glucocorticoid-associated osteonecrosis of the femoral head via the GHSR1a/Akt pathway. Commun Biol 2024; 7:132. [PMID: 38278996 PMCID: PMC10817896 DOI: 10.1038/s42003-024-05795-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 01/09/2024] [Indexed: 01/28/2024] Open
Abstract
Long-term use of glucocorticoids (GCs) is known to be a predominant cause of osteonecrosis of the femoral head (ONFH). Moreover, GCs can mediate apoptosis of various cell types by exaggerating oxidative stress. We have previously found that Cortistatin (CST) antagonizes oxidative stress and improves cell apoptosis in several conditions. In this study, we detected that the CST expression levels were diminished in patients with ONFH compared with femoral neck fracture (FNF). In addition, a GC-induced rat ONFH model was established, which impaired bone quality in the femoral head. Then, administration of CST attenuated these ONFH phenotypes. Furthermore, osteoblast and endothelial cells were cultured and stimulated with dexamethasone (Dex) in the presence or absence of recombinant CST. As a result, Dex induced impaired anabolic metabolism of osteoblasts and suppressed tube formation in endothelial cells, while additional treatment with CST reversed this damage to the cells. Moreover, blocking GHSR1a, a well-accepted receptor of CST, or blocking the AKT signaling pathway largely abolished the protective function of CST in Dex-induced disorder of the cells. Taken together, we indicate that CST has the capability to prevent GC-induced apoptosis and metabolic disorder of osteoblasts in the pathogenesis of ONFH via the GHSR1a/AKT signaling pathway.
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Affiliation(s)
- Yuan Gao
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China
| | - Yunhao You
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China
- Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Pengfei Zhang
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China
- Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yang Yu
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China
- Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zhaoning Xu
- Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Hui Wei
- Department of Rehabilitation, Qilu Hospital of Shandong University, Jinan, China
| | - Zhicheng Liu
- Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Pathology, Qilu Hospital of Shandong University, Jinan, China
| | - Ruixuan Yu
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China
- Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Gaoxin Jin
- Cheeloo College of Medicine, Shandong University, Jinan, China
- Department of Pathology, Qilu Hospital of Shandong University, Jinan, China
| | - Hao Wang
- Department of Trauma Orthopedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
| | - Shuai Zhang
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China.
| | - Yuhua Li
- Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, China.
| | - Weiwei Li
- Department of Pathology, Qilu Hospital of Shandong University, Jinan, China.
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Tsubosaka M, Maruyama M, Lui E, Kushioka J, Toya M, Gao Q, Shen H, Li X, Chow SKH, Zhang N, Yang YP, Goodman SB. Preclinical models for studying corticosteroid-induced osteonecrosis of the femoral head. J Biomed Mater Res B Appl Biomater 2024; 112:e35360. [PMID: 38247252 DOI: 10.1002/jbm.b.35360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 11/02/2023] [Accepted: 11/27/2023] [Indexed: 01/23/2024]
Abstract
Nontraumatic osteonecrosis of the femoral head (ONFH) is a refractory condition that commonly results in femoral head collapse and degenerative arthritis of the hip. In the early stages, surgical procedures for hip preservation, including core decompression (CD), have been developed to prevent progressive collapse of the femoral head. Optimization of bone regeneration and biological augmentation may further enhance the therapeutic efficacy of CD for ONFH. Thus, combining CD with cell-based therapy has recently been proposed. In fact, patients treated with cell-based therapy using autologous bone marrow concentrate demonstrate improved survivorship of the femoral head, compared with conventional CD alone. Preclinical research studies to investigate adjunctive therapies for CD often utilize the rabbit model of corticosteroid-induced ONFH. Mesenchymal stem cells (MSCs) are known to promote osteogenesis and angiogenesis, and decrease inflammation in bone. Local drug delivery systems have the potential to achieve targeted therapeutic effects by precisely controlling the drug release rate. Scaffolds can provide an osteoconductive structural framework to facilitate the repair of osteonecrotic bone tissue. We focused on the combination of both cell-based and scaffold-based therapies for bone tissue regeneration in ONFH. We hypothesized that combining CD and osteoconductive scaffolds would provide mechanical strength and structural cell guidance; and that combining CD and genetically modified (GM) MSCs to express relevant cytokines, chemokines, and growth factors would promote bone tissue repair. We developed GM MSCs that overexpress the anti-inflammatory, pro-reconstructive cytokines platelet-derived growth factor-BB to provide MSCs with additional benefits and investigated the efficacy of combinations of these GM MSCs and scaffolds for treatment of ONFH in skeletally mature male New Zealand white rabbits. In the future, the long-term safety, efficacy, durability, and cost-effectiveness of these and other biological and mechanical treatments must be demonstrated for the patients affected by ONFH.
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Affiliation(s)
- Masanori Tsubosaka
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Masahiro Maruyama
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Elaine Lui
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
- Department of Mechanical Engineering, Stanford University School of Engineering, Stanford, California, USA
| | - Junichi Kushioka
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Masakazu Toya
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Qi Gao
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Huaishuang Shen
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Xueping Li
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Simon Kwoon-Ho Chow
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Ning Zhang
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
| | - Yunzhi Peter Yang
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
- Department of Material Science and Engineering, Stanford University School of Medicine, Stanford, California, USA
- Department of Bioengineering, Stanford University School of Medicine, Stanford, California, USA
| | - Stuart B Goodman
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA
- Department of Bioengineering, Stanford University School of Medicine, Stanford, California, USA
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Chen H, Xue P, Xi H, He S, Sun G, Liu X, Du B. Predicting efficacy and guiding procedure choice in non-vascularized bone grafting: a CT Radiomics and clinical predictor approach. BMC Musculoskelet Disord 2023; 24:959. [PMID: 38082281 PMCID: PMC10712171 DOI: 10.1186/s12891-023-07095-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 12/04/2023] [Indexed: 12/18/2023] Open
Abstract
OBJECTIVES There is no practical approach for accurately predicting the efficacy of non-vascularized bone grafting (NVBG) and guiding its optimal procedure. MATERIALS AND METHODS This study enrolled 153 patients with 182 hips that underwent NVBG procedures. The patients were randomly divided into a training cohort (n = 130) and a validation cohort (n = 52). In the training cohort, radiomics model, clinical model, and combined radiomics-clinical (C-R) model were constructed using Rad-scores and clinical predictors to predict the efficacy of NVBG. The optimal model was visualized by a nomogram and assessed by decision curve analysis (DCA). 128 hips that underwent successful NVBG were then randomized into a new training cohort (n = 92) and a new validation cohort (n = 36), and three models were constructed and validated to predict the choice of NVBG procedure. RESULTS Japanese Investigation Committee (JIC) classification, exposure to risk factors postoperative, and Rad-scores consisting of four radiomics features were independent predictors for the efficacy of NVBG (P < 0.05). The C-R model provided better performance in both the training cohort (AUC: 0.818) and validation cohort (AUC: 0.747). To predict the choice of NVBG procedure, the C-R model built by JIC classification and Rad-scores consisting of five radiomics features showed the finest performance in both cohorts (AUC: 0.860 and 0.800, respectively). DCA showed great benefit using the C-R model for the choice of NVBG procedure. CONCLUSION The approach integrated by CT radiomics and clinical predictors can be visually and quantitatively applied to predict the efficacy and guide the choice of NVBG procedure with great predictive accuracy.
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Affiliation(s)
- Hao Chen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, China
| | - Peng Xue
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, China
| | - Hongzhong Xi
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, China
| | - Shuai He
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, China
| | - Guangquan Sun
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, China
| | - Xin Liu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, China
| | - Bin Du
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210029, China.
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Meng Q, Wang Y, Yuan T, Su Y, Li Z, Sun S. Osteoclast: The novel whistleblower in osteonecrosis of the femoral head. GENE REPORTS 2023; 33:101833. [DOI: 10.1016/j.genrep.2023.101833] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Liang XZ, Li N, Chai JL, Li W, Luo D, Li G. Knowledge mapping of programmed cell death in osteonecrosis of femoral head: a bibliometric analysis (2000-2022). J Orthop Surg Res 2023; 18:864. [PMID: 37957649 PMCID: PMC10644483 DOI: 10.1186/s13018-023-04314-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Osteonecrosis of the femoral head (ONFH) is a common, refractory and disabling disease of orthopedic department, which is one of the common causes of hip pain and dysfunction. Recent studies have shown that much progress has been made in the research of programmed cell death (PCD) in ONFH. However, there is no bibliometric analysis in this research field. This study aims to provide a comprehensive overview of the knowledge structure and research hot spots of PCD in ONFH through bibliometrics. METHOD The literature search related to ONFH and PCD was conducted on the Web of Science Core Collection (WoSCC) database from 2002 to 2021. The VOSviewers, "bibliometrix" R package and CiteSpace were used to conduct this bibliometric analysis. RESULTS In total, 346 articles from 27 countries led by China and USA and Japan were included. The number of publications related to PCD in ONFH is increasing year by year. Shanghai Jiao Tong University, Xi An Jiao Tong University, Wuhan University and Huazhong University of Science and Technology are the main research institutions. Molecular Medicine Reports is the most popular journal in the field of PCD in ONFH, and Clinical Orthopaedics and Related Research is the most cocited journal. These publications come from 1882 authors among which Peng Hao, Sun Wei, Zhang Chang-Qing, Zhang Jian and Wang Kun-zheng had published the most papers and Ronald S Weinstein was cocited most often. Apoptosis, osteonecrosis, osteonecrosis of the femoral head, glucocorticoid and femoral head appeared are the main topics the field of PCD in ONFH. Autophagy was most likely to be the current research hot spot for PCD in ONFH. CONCLUSION This is the first bibliometric study that comprehensively summarizes the research trends and developments of PCD in ONFH. This information identified recent research frontiers and hot directions, which will provide a reference for scholars studying PCD in ONFH.
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Affiliation(s)
- Xue-Zhen Liang
- First College of Clinical Medicine, Orthopaedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jingshi Road, 16369, Jinan, 250014, Shandong, China
- The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan , 250355, Shandong, China
| | - Nan Li
- Orthopedics, Liaocheng Hospital of Traditional Chinese Medicine, Liaocheng, 252000, Shandong, China
| | - Jin-Lian Chai
- College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Wei Li
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China
| | - Di Luo
- The First Clinical Medical School, Shandong University of Traditional Chinese Medicine, Jinan , 250355, Shandong, China
| | - Gang Li
- First College of Clinical Medicine, Orthopaedic Microsurgery, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jingshi Road, 16369, Jinan, 250014, Shandong, China.
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Shan H, Lin Y, Yin F, Pan C, Hou J, Wu T, Xia W, Zuo R, Cao B, Jiang C, Zhou Z, Yu X. Effects of astragaloside IV on glucocorticoid-induced avascular necrosis of the femoral head via regulating Akt-related pathways. Cell Prolif 2023; 56:e13485. [PMID: 37186483 PMCID: PMC10623974 DOI: 10.1111/cpr.13485] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Revised: 03/27/2023] [Accepted: 04/12/2023] [Indexed: 05/17/2023] Open
Abstract
We investigated the role of astragaloside IV (AS-IV) in preventing glucocorticoid-induced avascular necrosis of the femoral head (ANFH) and the underlying molecular mechanisms. Network pharmacology was used to predict the molecular targets of AS-IV. Molecular dynamic simulations were performed to explore the binding mechanism and interaction mode between AS-IV and Akt. Rat models of glucocorticoid-induced ANFH with AS-IV intervention were established, and osteogenesis, angiogenesis, apoptosis and oxidative stress were evaluated before and after blocking the PI3K/Akt pathway with LY294002. The effects of glucocorticoid and AS-IV on bone marrow mesenchymal stem cells and human umbilical vein endothelial cells incubated with and without LY294002 were determined. Downregulated p-Akt expression could be detected in the femoral heads of glucocorticoid-induced ANFH patients and rats. AS-IV increased trabecular bone integrity and vessel density of the femoral head in the model rats. AS-IV increased Akt phosphorylation and upregulated osteogenesis-, angiogenesis-, apoptosis- and oxidative stress-related proteins and mRNA and downregulated Bax, cleaved caspase-3 and cytochrome c levels. AS-IV promoted human umbilical vein endothelial cell migration, proliferation and tube formation ability; bone marrow mesenchymal stem cell proliferation; and osteogenic differentiation under glucocorticoid influence. AS-IV inhibited apoptosis. LY294002 inhibited these effects. AS-IV prevented glucocorticoid-induced ANFH by promoting osteogenesis and angiogenesis via the Akt/Runx2 and Akt/HIF-1α/VEGF pathways, respectively, and suppressing apoptosis and oxidative stress via the Akt/Bad/Bcl-2 and Akt/Nrf2/HO-1 pathways, respectively.
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Affiliation(s)
- Haojie Shan
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Yiwei Lin
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Fuli Yin
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Chenhao Pan
- Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongSARChina
| | - Jianzhong Hou
- Department of General Surgery, Shanghai Fengxian Central HospitalShanghai Jiao Tong University Affiliated Sixth People's Hospital South CampusShanghaiChina
| | - Tianyi Wu
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Wenyang Xia
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Rongtai Zuo
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Bojun Cao
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
| | - Chaolai Jiang
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Zubin Zhou
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
| | - Xiaowei Yu
- Department of Orthopaedic SurgeryShanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina
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Wang T, Gao C, Wu D, Li C, Cheng X, Yang Z, Zhang Y, Zhu Y. One-year unplanned readmission after total hip arthroplasty in patients with osteonecrosis of the femoral head: rate, causes, and risk factors. BMC Musculoskelet Disord 2023; 24:845. [PMID: 37884992 PMCID: PMC10605627 DOI: 10.1186/s12891-023-06968-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/15/2023] [Indexed: 10/28/2023] Open
Abstract
BACKGROUND The primary objectives of this study were to focus on one - year unplanned readmissions after THA in ONFH patients and to investigate rates, causes, and independent risk factors. METHODS Between October 2014 and April 2019, eligible patients undergoing THA were enrolled and divided into unplanned readmission within one year and no readmission in this study. All unplanned readmissions within 1 year of discharge were reviewed for causes and the rate of unplanned readmissions was calculated. Demographic information, ONFH characteristics, and treatment-related variables of both groups were compared and analysed. RESULTS Finally, 41 out of 876 patients experienced unplanned readmission. The readmission rate was 1.83% in 30 days 2.63% in 90 days, and 4.68% in 1 year. Prosthesis dislocation was always the most common cause at all time points studied within a year. The final logistic regression model revealed that higher risks of unplanned readmission were associated with age > 60 years (P = 0.001), urban residence (P = 0.001), ARCO stage IV (P = 0.025), and smoking (P = 0.033). CONCLUSIONS We recommend the introduction of a strict smoking cessation program prior to surgery and the development of comprehensive management strategies, especially for the elderly and end-stage ONFH patients, and pay more attention to preventing prosthesis dislocation in the early days after surgery.
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Affiliation(s)
- Tianyu Wang
- Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, NO.139 Ziqiang Road, Shijiazhuang, 050051, P.R. China
| | - Congliang Gao
- Department of Orthopaedic Surgery, Huai'an Hospital of Huai'an City, Huai'an, Jiangsu, 223200, P.R. China
| | - Dongwei Wu
- Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, NO.139 Ziqiang Road, Shijiazhuang, 050051, P.R. China
| | - Chengsi Li
- Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, NO.139 Ziqiang Road, Shijiazhuang, 050051, P.R. China
| | - Xinqun Cheng
- Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, NO.139 Ziqiang Road, Shijiazhuang, 050051, P.R. China
| | - Zhenbang Yang
- Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, NO.139 Ziqiang Road, Shijiazhuang, 050051, P.R. China
| | - Yingze Zhang
- Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, NO.139 Ziqiang Road, Shijiazhuang, 050051, P.R. China.
| | - Yanbin Zhu
- Department of Orthopaedics, the 3rd Hospital, Hebei Medical University, NO.139 Ziqiang Road, Shijiazhuang, 050051, P.R. China.
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Sun K, Xue Y, Zhang X, Li X, Zhao J, Xu X, Zhang X, Yang F. Tanshinone I alleviates steroid-induced osteonecrosis of femoral heads and promotes angiogenesis: in vivo and in vitro studies. J Orthop Surg Res 2023; 18:474. [PMID: 37391758 DOI: 10.1186/s13018-023-03934-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Accepted: 06/16/2023] [Indexed: 07/02/2023] Open
Abstract
BACKGROUND The impaired blood supply to the bones is an important pathological feature of steroid-induced osteonecrosis of the femoral head (SIONFH). Danshen is a Chinese herb that shows therapeutic effects on SIONFH, but the effects of one of its major bioactive constituents, Tanshinone I (TsI), on SIONFH remain unknown. Here, we evaluated the effects of TsI on SIONFH, particularly focusing on its effects on angiogenesis, in in vivo and in vitro research. METHODS SIONFH was induced in Sprague-Dawley rats by an intramuscular injection of methylprednisolone (40 mg/kg) in combination with an intraperitoneal injection of lipopolysaccharide (20 μg/kg). Morphological alterations of the femoral head were observed by dual-energy X-ray absorptiometry and HE staining. Western blot, qRT-PCR, and immunohistochemical/immunofluorescence staining were used to determine gene expression. RESULTS TsI (10 mg/kg) alleviated bone loss and rescued the expression of angiogenesis-related molecules (CD31, VWF, VEGF, and VEGFR2) in the femoral heads of SIONFH rats. Notably, TsI rescued the down-regulated expression of SRY-box transcription factor 11 (SOX11) in CD31+ endothelial cells in the femoral heads of SIONFH rats. In vitro studies showed that TsI preserved the dexamethasone-harmed angiogenic property (migration and tube formation) of human umbilical vein cells (EA.hy926), suppressed dexamethasone-induced cell apoptosis, reduced pro-apoptotic proteins (cytosolic cytochrome C, Bax, and caspase 3/9) and increased anti-apoptotic protein Bcl-2, whereas silencing of SOX11 reversed these beneficial effects. CONCLUSIONS This study demonstrates that TsI alleviates SIONFH and promotes angiogenesis by regulating SOX11 expression. Our work would provide new evidence for the application of TsI to treat SIONFH.
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Affiliation(s)
- Kai Sun
- The First Department of Orthopedics and Traumatology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Yuman Xue
- The Second Department of Rehabilitation, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Xin Zhang
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Xiaodong Li
- The Third Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Jun Zhao
- Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Xilin Xu
- The Third Department of Orthopedics and Traumatology, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China
| | - Xiaofeng Zhang
- Teaching and Research Section of Orthopedics and Traumatology, Heilongjiang University of Chinese Medicine, No. 24, Heping Road, Harbin, Heilongjiang, China
| | - Fubiao Yang
- President's Office, The Third Affiliated Hospital, Heilongjiang University of Chinese Medicine, No. 2, Xiangjiang Road, Harbin, Heilongjiang, China.
- Teaching and Research Section of Orthopedics and Traumatology, Heilongjiang University of Chinese Medicine, No. 24, Heping Road, Harbin, Heilongjiang, China.
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Yue J, Guo X, Wang R, Li B, Sun Q, Liu W, Chen J, Zhao F. Reliability and repeatability of 2021 ARCO classification and its guiding significance in treatment of nontraumatic osteonecrosis of the femoral head. BMC Musculoskelet Disord 2023; 24:469. [PMID: 37291529 DOI: 10.1186/s12891-023-06587-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 05/31/2023] [Indexed: 06/10/2023] Open
Abstract
BACKGROUND The study was designed to evaluate the interobserver reliability and intraobserver repeatability of the 2021 Association Research Circulation Osseous (ARCO) classification and explore its guiding significance in the treatment of nontraumatic osteonecrosis of the femoral head (ONFH). METHODS In this retrospective study, we randomly selected and investigated 50 sets of preoperative computed tomography or magnetic resonance imaging scans from 96 patients (139 hips) to validate the reliability and repeatability of the 2021 ARCO classification. Patients with a nano-hydroxyapatite/polyamide-66 support rod were included in the clinical efficacy study. The Harris hip score (HHS) was used to assess hip function. Femoral head collapse of > 2 mm was considered radiological failure. Total hip arthroplasty (THA) was performed for clinical failure, and follow-up was discontinued. RESULTS The average kappa value of interobserver consistency was 0.652. The average rate of consistency was 90.25%, and the average kappa value of intraobserver consistency was 0.836. Eighty-two patients (122 hips) were enrolled and followed up for a mean of 43.57 ± 9.64 months. There was no significant difference in the HHS among the three groups before surgery, but the difference was statistically significant at the last follow-up. Among them, types 1 and 2 had significantly higher scores at the last follow-up than preoperatively (P < 0.05), whereas type 3 had a lower score at the last follow-up than preoperatively, although the difference was not statistically significant (P > 0.05).According to the imaging evaluation, the failure rate of type 1, 2, and 3 at the last follow-up was 0%, 19%, and 87%, respectively. Univariate analysis showed that the femoral head survival rate of radiography was significantly affected by the new classification system (P = 0.00). At the last follow-up, the incidence rate of THA in type 1, 2, and 3 was 5%, 7%, and 31%, respectively. Univariate analysis showed that the femoral head survival rate was significantly affected by the new classification system (P = 0.001). CONCLUSIONS The 2021 ARCO classification for early-stage ONFH shows substantial consistency and repeatability. We do not recommend femoral head-preserving surgery for patients with type 3 ONFH.
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Affiliation(s)
- Ju'an Yue
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Xiaozhong Guo
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China.
| | - Randong Wang
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Bing Li
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Qiang Sun
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Wangyan Liu
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Jiao Chen
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
| | - Fengnian Zhao
- Department of Joint Surgery, Aviation General Hospital, Courtyard 3, Anwai Beiyuan, Chaoyang District, Beijing, China
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Doghish AS, Elballal MS, Elazazy O, Elesawy AE, Shahin RK, Midan HM, Sallam AAM, Elbadry AM, Mohamed AK, Ishak NW, Hassan KA, Ayoub AM, Shalaby RE, Elrebehy MA. miRNAs as potential game-changers in bone diseases: Future medicinal and clinical uses. Pathol Res Pract 2023; 245:154440. [PMID: 37031531 DOI: 10.1016/j.prp.2023.154440] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 03/30/2023] [Accepted: 04/02/2023] [Indexed: 04/08/2023]
Abstract
MicroRNAs (miRNAs), short, highly conserved non-coding RNA, influence gene expression by sequential mechanisms such as mRNA breakdown or translational repression. Many biological processes depend on these regulating substances, thus changes in their expression have an impact on the maintenance of cellular homeostasis and result in the emergence of a variety of diseases. Relevant studies have shown in recent years that miRNAs are involved in many stages of bone development and growth. Additionally, abnormal production of miRNA in bone tissues has been closely associated with the development of numerous bone disorders, such as osteonecrosis, bone cancer, and bone metastases. Many pathological processes, including bone loss, metastasis, the proliferation of osteosarcoma cells, and differentiation of osteoblasts and osteoclasts, are under the control of miRNAs. By bringing together the most up-to-date information on the clinical relevance of miRNAs in such diseases, this study hopes to further the study of the biological features of miRNAs in bone disorders and explore their potential as a therapeutic target.
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Luo H, Le G, Lu M, Li L. The Lnc-HOTAIR/miR122/PPARγ signaling mediated the occurrence and continuous development of alcohol-induced Osteonecrosis of the femoral head. Toxicol Lett 2023; 380:53-61. [PMID: 37024064 DOI: 10.1016/j.toxlet.2023.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 02/09/2023] [Accepted: 04/03/2023] [Indexed: 04/08/2023]
Abstract
This study aimed to explore the mechanism of alcohol-induced Osteonecrosis of the femoral head (ONFH) through in vivo and in vitro experiments. In vitro, the Oil Red O staining showed that ethanol promoted extracellular adipogenesis in a dose-dependent manner. ALP staining and alizarin red staining showed that ethanol inhibited the formation of extracellular mineralization in a dose-dependent manner. The Oil Red O staining showed that miR122 mimics and Lnc-HOTAIR SiRNA rescued extracellular adipogenesis induced by ethanol in BMSCs. Besides, we found that the high expression of PPARγ in BMSCs recruited histone deacetylase 3 (HDAC3) and histone methyltransferase (SUV39H1), which reduced the histone acetylation level and increased the histone methylation level in the miR122 promoter region, respectively. In vivo, the levels of H3K9ac, H3K14ac, and H3K27ac of miR122 promoter region in the ethanol group were significantly decreased compared to the control group, respectively. The levels of H3K9me2 and H3K9me3 of miR122 promoter region in the ethanol group were significantly increased compared to the control group. Lnc-HOTAIR/miR-122/PPARγ signaling mediated the alcohol-induced ONFH in the rat model. Furthermore, the persistent decrease of miR122 expression mediated the continuous progress of alcohol-induced ONFH after stopping alcohol consumption.
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Affiliation(s)
- Hanwen Luo
- Department of Joint Osteopathy, Liuzhou Worker's Hospital, Liuzhou, Guangxi 545000, China.
| | - Guoping Le
- Department of Joint Osteopathy, Liuzhou Worker's Hospital, Liuzhou, Guangxi 545000, China
| | - Mengting Lu
- Department of Joint Osteopathy, Liuzhou Worker's Hospital, Liuzhou, Guangxi 545000, China
| | - Li Li
- Department of Joint Osteopathy, Liuzhou Worker's Hospital, Liuzhou, Guangxi 545000, China
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Bian Y, Hu T, Lv Z, Xu Y, Wang Y, Wang H, Zhu W, Feng B, Liang R, Tan C, Weng X. Bone tissue engineering for treating osteonecrosis of the femoral head. EXPLORATION (BEIJING, CHINA) 2023; 3:20210105. [PMID: 37324030 PMCID: PMC10190954 DOI: 10.1002/exp.20210105] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 05/12/2022] [Indexed: 06/16/2023]
Abstract
Osteonecrosis of the femoral head (ONFH) is a devastating and complicated disease with an unclear etiology. Femoral head-preserving surgeries have been devoted to delaying and hindering the collapse of the femoral head since their introduction in the last century. However, the isolated femoral head-preserving surgeries cannot prevent the natural progression of ONFH, and the combination of autogenous or allogeneic bone grafting often leads to many undesired complications. To tackle this dilemma, bone tissue engineering has been widely developed to compensate for the deficiencies of these surgeries. During the last decades, great progress has been made in ingenious bone tissue engineering for ONFH treatment. Herein, we comprehensively summarize the state-of-the-art progress made in bone tissue engineering for ONFH treatment. The definition, classification, etiology, diagnosis, and current treatments of ONFH are first described. Then, the recent progress in the development of various bone-repairing biomaterials, including bioceramics, natural polymers, synthetic polymers, and metals, for treating ONFH is presented. Thereafter, regenerative therapies for ONFH treatment are also discussed. Finally, we give some personal insights on the current challenges of these therapeutic strategies in the clinic and the future development of bone tissue engineering for ONFH treatment.
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Affiliation(s)
- Yixin Bian
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Tingting Hu
- State Key Laboratory of Chemical Resource EngineeringBeijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing University of Chemical TechnologyBeijingChina
| | - Zehui Lv
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Yiming Xu
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Yingjie Wang
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Han Wang
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Wei Zhu
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Bin Feng
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
| | - Ruizheng Liang
- State Key Laboratory of Chemical Resource EngineeringBeijing Advanced Innovation Center for Soft Matter Science and EngineeringBeijing University of Chemical TechnologyBeijingChina
| | - Chaoliang Tan
- Department of ChemistryCity University of Hong KongKowloonHong Kong SARChina
| | - Xisheng Weng
- Department of Orthopedic SurgeryState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina
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Li G, Ji F, Guo W, Wei B. Decreased serum MMP-9 levels in patients with nontraumatic osteonecrosis of the femoral head. BMC Musculoskelet Disord 2023; 24:240. [PMID: 36991363 PMCID: PMC10053116 DOI: 10.1186/s12891-023-06342-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Accepted: 03/20/2023] [Indexed: 03/31/2023] Open
Abstract
BACKGROUND Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) are involved in the pathological mechanism of osteonecrosis of the femoral head (ONFH). This study aimed to investigate the relationship of serum MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio with disease severity in patients with nontraumatic ONFH. METHODS Serum levels of MMP-9 and TIMP-1 among 102 nontraumatic ONFH patients and 96 healthy individuals were determined by enzyme-linked immunosorbent assay (ELISA). Imaging severity was determined using the FICAT classification system. The Harris hip score (HHS) and visual analogue scale (VAS) were used to evaluate clinical progress. The correlations of serum MMP-9 and TIMP-1 levels with imaging severity and clinical progress was evaluated statistically. The diagnostic value of MMP-9 for NONFH disease severity was evaluated by examining receiver operating characteristic (ROC) curves. RESULTS The serum MMP-9 levels and the MMP-9/TIMP-1 ratio were significantly increased in patients with ONFH compared to normal controls, and TIMP-1 levels did not differ between the two groups. Serum MMP-9 levels and the MMP-9/TIMP-1 ratio were positively correlated with FICAT stage and VAS and were negatively correlated with the HHS score. The ROC curve results indicated that MMP-9 could be used as a potential marker of nontraumatic ONFH imaging progression. CONCLUSIONS We hypothesize that increased MMP-9 expression and an imbalance in the MMP-9/TIMP-1 ratio play a role in the development of ONFH and are correlate with the severity of ONFH. The determination of MMP-9 can be a useful tool to assess the severity of the disease in patients with nontraumatic ONFH.
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Affiliation(s)
- Guopeng Li
- Weifang Medical University, Weifang, Shandong Province, China
- Department of Orthopedics, Linyi People's Hospital, Jie Fang Road East, No.27, Linyi, 276003, Shandong, China
| | - Fengxuan Ji
- Jinzhou Medical University, Jinzhou, Liaoning Province, China
| | - Wenchao Guo
- Weifang Medical University, Weifang, Shandong Province, China
| | - Biaofang Wei
- Department of Orthopedics, Linyi People's Hospital, Jie Fang Road East, No.27, Linyi, 276003, Shandong, China.
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Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism. Biomedicines 2023; 11:biomedicines11030873. [PMID: 36979852 PMCID: PMC10045807 DOI: 10.3390/biomedicines11030873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/08/2023] [Accepted: 03/09/2023] [Indexed: 03/16/2023] Open
Abstract
Osteonecrosis of the femoral head (ONFH) is a common disabling disease. Copper has positive effects on cells that regulate bone metabolism. However, the relationship between copper metabolism (CM) and steroid-induced ONFH (SONFH) remains unclear. The GSE123568 dataset was downloaded from the Gene Expression Omnibus. The differentially expressed CM-related SONFH genes (DE-CMR-SONFHGs) were identified via differential analysis and weighted gene coexpression network analysis (WGCNA). Receiver operating characteristic (ROC) analysis was performed for the predictive accuracy of key genes. Targeting drugs and the copper death-related genes (CDRGs) relevant to key genes were investigated. The bioinformatics results were confirmed via quantitative real-time polymerase chain reaction (qRT–PCR) and Western blot (WB) analysis. Two out of 106 DE-CMR-SONFHGs were identified as key genes (PNP and SLC2A1), which had diagnostic value in distinguishing SONFH from control samples and were related to various immune cell infiltrations. Eleven PMP-targeting drugs and five SLC2A1-targeting drugs were identified. The qRT–PCR, as well as WB, results confirmed the downregulation PNP and SLC2A1 and high expression of the CDRGs DLD, PDHB, and MTF1, which are closely related to these two key genes. In conclusion, PNP and SLC2A1 were identified as key genes related to SONFH and may provide insights for SONFH treatment.
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Accumulation of Fat Not Responsible for Femoral Head Necrosis, Revealed by Single-Cell RNA Sequencing: A Preliminary Study. Biomolecules 2023; 13:biom13010171. [PMID: 36671556 PMCID: PMC9856115 DOI: 10.3390/biom13010171] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 01/09/2023] [Accepted: 01/10/2023] [Indexed: 01/18/2023] Open
Abstract
The etiology of osteonecrosis of the femoral head (ONFH) is not yet fully understood. However, ONFH is a common disease with high morbidity, and approximately one-third of cases are caused by glucocorticoids. We performed single-cell RNA sequencing of bone marrow to explore the effect of glucocorticoid on ONFH. Bone marrow samples of the proximal femur were extracted from four participants during total hip arthroplasty, including two participants diagnosed with ONFH for systemic lupus erythematosus (SLE) treated with glucocorticoids (the case group) and two participants with femoral neck fracture (the control group). Unbiased transcriptome-wide single-cell RNA sequencing analysis and computational analyses were performed. Seventeen molecularly defined cell types were identified in the studied samples, including significantly dysregulated neutrophils and B cells in the case group. Additionally, fatty acid synthesis and aerobic oxidation were repressed, while fatty acid beta-oxidation was enhanced. Our results also preliminarily clarified the roles of the inflammatory response, substance metabolism, vascular injury, angiogenesis, cell proliferation, apoptosis, and dysregulated coagulation and fibrinolysis in glucocorticoid-induced ONFH. Notably, we list the pathways that were markedly altered in glucocorticoid-induced ONFH with SLE compared with femoral head fracture, as well as their common genes, which are potential early therapeutic targets. Our results provide new insights into the mechanism of glucocorticoid-induced ONFH and present potential clues for effective and functional manipulation of human glucocorticoid-induced ONFH, which could improve patient outcomes.
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Wei W, Tan B, Yan Y, Li W, Zeng X, Chen Q, Wang R, He H, Qin L, Li T, Chen W. Hip Preservation or Total Hip Arthroplasty? A Retrospective Case-Control Study of Factors Influencing Arthroplasty Decision-Making for Patients with Osteonecrosis of the Femoral Head in China. Orthop Surg 2023; 15:731-739. [PMID: 36625784 PMCID: PMC9977578 DOI: 10.1111/os.13639] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 11/23/2022] [Accepted: 11/27/2022] [Indexed: 01/11/2023] Open
Abstract
OBJECTIVE At present, there is no consensus or guidance on indications for osteonecrosis of the femoral head (ONFH) patients to receive hip arthroplasty (THA) treatment. This study aims to explore the factors that influence the decision-making for THA in patients with ONFH, and to provide references for clinical decision for ONFH patients to be indicated for THA or hip preservation. METHODS This retrospective case-control study involved data for ONFH patients from July 2016 to October 2021 from the China Osteonecrosis of the Femoral Head Database (CONFHD). The patients with ONFH, and unilateral hip affected at the first visit were divided into THA group and non-THA group according to if they had undergone THA treatment. The differences between the two groups of patients in terms of gender, age at the time of consultation, body mass index (BMI), etiology, onset side, association research circulation osseous (ARCO) stage, hip joint function, visual analog scale (VAS), etc. were analyzed. Multivariate binomial logistic regression analysis was then applied to evaluate the risk factors of ONFH patients who underwent THA during the first visit. RESULTS A total of 640 patients were recruited for analysis, including 209 cases from the THA group and 431 cases from the non-THA group. The results of univariate analysis showed that the two groups of patients were significantly different in the following six indicators: age (59 vs. 46, Z = -9.58, p < 0.001), duration of disease (78 vs. 17, Z = -16.14, p < 0.001), gender composition (χ2 = 8.09, p = 0.004), disease etiology (χ2 = 33.04, p < 0.001), ARCO stage (χ2 = 334.86, p < 0.001), flexion of hip joint (χ2 = 172.33, p < 0.001). However, the comparison between the two groups on VAS (Z = -0.82, p = 0.41), BMI (Z = -1.35, p = 0.18), and onset side (χ2 = 1.53, p = 0.22) did not obviously differ. The results regression analysis showed that the age at the time of consultation, duration of disease, ARCO stage, and the hip joint function affected the decision making if the patients should undergo THA. The results of receiver operating characteristic curve (ROC) analysis showed that aforementioned indicators were satisfactory in predicting whether patients with ONFH would be treated with THA. The regression model using the above four indicators as comprehensive indicators has satisfactory performance in predicting whether to perform THA, and the area under the curve (AUC) is 93.94%. CONCLUSION These factors such as age, duration of disease, ARCO stage, and hip flexion function should be considered comprehensively before making decisions to perform THA or not in our clinical practice.
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Affiliation(s)
- Wei Wei
- The Third Affiliated Hospital of Beijing University of Chinese MedicineBeijingChina
| | - Biao Tan
- Chongqing Traditional Chinese Medicine HospitalChongqingChina,Wangjing HospitalChina Academy of Chinese Medical SciencesBeijingChina
| | - Yan Yan
- The Third Affiliated Hospital of Beijing University of Chinese MedicineBeijingChina
| | | | - Xiangrong Zeng
- Guizhou University of Traditional Chinese MedicineGuiyangChina
| | - Qianglong Chen
- Guizhou University of Traditional Chinese MedicineGuiyangChina
| | - Rongtian Wang
- The Third Affiliated Hospital of Beijing University of Chinese MedicineBeijingChina
| | - Haijun He
- Wangjing HospitalChina Academy of Chinese Medical SciencesBeijingChina
| | - Ling Qin
- Department of Orthopaedics & Traumatology, Musculoskeletal Research LaboratoryInnovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health, The Chinese University of Hong Kong, Hong Kong Special Administrative RegionChina,Translational Medicine R&D CenterShenzhen Institutes of Advanced Technology, Chinese Academy of SciencesShenzhenChina
| | - Taixian Li
- The Third Affiliated Hospital of Beijing University of Chinese MedicineBeijingChina
| | - Weiheng Chen
- The Third Affiliated Hospital of Beijing University of Chinese MedicineBeijingChina
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Cuenca-Gómez J, Ocaña-Losada C, Crujeiras P, Rodrigues D, Martínez-Espinosa M. Etiología de la osteonecrosis avascular de cadera y hombro. Cribado de la enfermedad de Gaucher. Rev Clin Esp 2022. [DOI: 10.1016/j.rce.2022.10.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Dubinin AO, Khramov AE, Dubinina TV, Ilinykh EV, Bialik EI. Intraoperative picture of hip joint lesion in ankylosing spondylitis: data from a retrospective analysis. RHEUMATOLOGY SCIENCE AND PRACTICE 2022. [DOI: 10.47360/1995-4484-2022-594-598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
In population of Russian patients with ankylosing spondylitis (AS), the frequency of clinical manifestations (pain and limitation of functions) of coxitis reaches 56%. Total hip arthroplasty (THA) can be considered as the only alternative that can relieve the suffering of the patient. Radiography and magnetic resonance imaging are widely used methods for assessing structural damage to the hip joint in AS. However, at the moment these methods can’t allow us to fully describe the lifetime changes of these joints. The aim of the study: to analyze the external changes of the femoral heads (HF) and acetabulums during the THA in patients with AS. Materials and methods. The retrospective study included 170 patients with a reliable diagnosis of AS, who met the modified New York criteria of 1984, who were treated in the traumatological and orthopedic department of the V.A. Nasonova Research Institute of Rheumatology in the period from 1998 to 2020, all patients underwent THA as planned. Most of them were male (80.6%). The average age of patients was 38.1±11.3 years and the average duration of the disease since the onset of the first symptoms was 17.0±8.5 years. The duration of pain in hip joints before performing THA is 7.4±4.8 years. The assessment of macroscopic changes in the FH and acetabulum was performed intraoperatively. Results and discussion. Acetabulum protrusion was detected in 108 (63.5%) patients, bone cysts – in 65 (38.2%). Filling of acetabulum with granulation tissue was recorded in 155 (91.2%) patients, presence of osteophytes on its edges – in 153 (90%). Cartilage in the acetabulum was completely absent in 122 (71.8%) patients. FH deformation was detected in 98.2% of cases, erosion in 46.4%. Cartilage on FH was completely absent in 130 (76.5%) patients. In 119 (70%) patients, macroscopic signs of osteonecrosis of FH were found. 79 (46.4%) patients had ankylosis of the hip joint, including fibrous ankylosis – in 77.2% of patients and bone ankylosis – in 22.8%. Conclusion. In patients with AS, the necessity for THA occurs on average after 7.4±4.8 years from the moment of the appearance of first clinical signs of coxitis. In 70% of cases, the macroscopic picture of hip joint lesion was characterized by the development of Avascular necrosis of the femur head (AVNFH), in most patients there was no cartilage in the most loaded segments of acetabulum and FH, in almost half of cases – ankylosis of hip joint and mainly fibrous (77.2%).
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Affiliation(s)
| | | | | | | | - E. I. Bialik
- V.A. Nasonova Research Institute of Rheumatology
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Yang X, Shi L, Zhang T, Gao F, Sun W, Wang P, Wu X, Li Z. High-energy focused extracorporeal shock wave prevents the occurrence of glucocorticoid-induced osteonecrosis of the femoral head: A prospective randomized controlled trial. J Orthop Translat 2022; 36:145-151. [PMID: 36263382 PMCID: PMC9550842 DOI: 10.1016/j.jot.2022.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 07/28/2022] [Accepted: 08/03/2022] [Indexed: 11/06/2022] Open
Abstract
Background Studies have shown that high-energy focused extracorporeal shock wave therapy (HF-ESWT) has a certain therapeutic effect on glucocorticoid-induced osteonecrosis of the femoral head (ONFH). This study aimed to observe the efficacy and safety of HF-ESWT as a precautionary measure to reduce the probability of glucocorticoid-induced ONFH. Methods A prospective randomized controlled trial was designed to evaluate whether HF-ESWT (Group A) can significantly prevent the incidence of glucocorticoid-induced ONFH relative to a control group without shockwave intervention (Group B). MRI was used to assess whether all participants experienced ONFH at 3, 6, and 12 months after the intervention. Continuous scoring was used to evaluate the intervention results: the 10-cm visual analog scale (VAS) was used to evaluate pain, and the hip Harris score (HHS) was used to evaluate the function of the hip joint. Any adverse events were recorded. Results 153 patients (89 females and 64 males) who had been allocated to group A (75 patients) or Group B (78 patients) were included in the final analysis. The patients were 45.0 ± 13.0 years old. There were significant differences between the two groups in MRI diagnosis of ONFH patients (2 cases in Group A, 9 cases in Group B; p = 0.034). Significant differences between groups were found in bilateral hip function measured using the HHS at 6 months (Left p = 0.026; Right p = 0.033) and 12 months (Left p = 0.018; Right p = 0.038). However, there was no difference in the functional results measured at 3 months and the VAS at any points. Conclusions This study confirms that HF-ESWT can be successfully used to reduce the probability of glucocorticoid-induced ONFH. Pain and hip dysfunction are common clinical manifestations when ONFH is unavoidable. Therefore, HF-ESWT can be recommended for the prevention and intervention of ONFH high-risk populations receiving high-dose glucocorticoid therapy. The Translational potential of this article The effective prevention of HF-ESWT on ONFH after high-dose glucocorticoid application demonstrated its transformation potential as a preventive method in the clinical prevention of glucocorticoid-induced ONFH.
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Affiliation(s)
- Xu Yang
- Department of Orthopedics, Peking University China-Japan Friendship Clinical Hospital, Beijing, 100029, China,Centre for Osteonecrosis and Joint-Preserving & Reconstruction, Orthopaedic Department, China-Japan Friendship Hospital, Beijing, 100029, China
| | - Lijun Shi
- Department of Orthopedic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan, China
| | - Tao Zhang
- Department of Chinese Medicine, The First Clinical School of Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China
| | - Fuqiang Gao
- Centre for Osteonecrosis and Joint-Preserving & Reconstruction, Orthopaedic Department, China-Japan Friendship Hospital, Beijing, 100029, China,Corresponding author.
| | - Wei Sun
- Centre for Osteonecrosis and Joint-Preserving & Reconstruction, Orthopaedic Department, China-Japan Friendship Hospital, Beijing, 100029, China,Corresponding author.
| | - Peixu Wang
- Centre for Osteonecrosis and Joint-Preserving & Reconstruction, Orthopaedic Department, China-Japan Friendship Hospital, Beijing, 100029, China
| | - Xinjie Wu
- Department of Molecular Medicine and Surgery, Karolinska Institute, 171 76, Stockholm, Sweden
| | - Zirong Li
- Centre for Osteonecrosis and Joint-Preserving & Reconstruction, Orthopaedic Department, China-Japan Friendship Hospital, Beijing, 100029, China
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Identification of Inflammation-Related Genes and Exploration of Regulatory Mechanisms in Patients with Osteonecrosis of the Femoral Head. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4501186. [PMID: 36193326 PMCID: PMC9526608 DOI: 10.1155/2022/4501186] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 08/11/2022] [Accepted: 08/26/2022] [Indexed: 11/18/2022]
Abstract
Background Osteonecrosis of the femoral head (ONFH) is a disabling orthopedic disease, which is impacted by infiltration of immune cells. Thus, the aim of the current research was to determine the inflammation-related biomarkers in ONFH. Methods GSE123568 dataset with control and steroid-induced osteonecrosis of the femoral head (SONFH) samples were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were detected by limma R package and weighted gene co-expression network analysis (WGCNA) was used to explore the co-expression genes and modules. We obtained inflammation-related genes (IRGs) from the Molecular Signatures Database (MSigDB). Then, the IRGs associated with SONFH (IRGs-SONFH) were screened out and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and hub genes were identified by the MCODE algorithm. Based on the hub genes, we constructed a lncRNA-miRNA-mRNA network. Results We identified 535 DEGs between control and SONFH samples. The WGCNA clearly indicated that the brown module was most significantly associated with SONFH. We identified 25 IRGs-SONFH through WGCNA module genes, DEGs and IRGs. A total of 4 hub genes (CD14, CYBB, NOD2, and TLR1) were identified by Cytoscape. Receiver operating characteristic (ROC) curve analysis determined that the expressions of the four genes could distinguish SONFH from controls as evidenced by the area under the curve (AUC) greater than 0.7. Finally, we constructed a competitive endogenous RNA (ceRNA) network which included 67 lncRNAs, 1 miRNA (hsa-miR-320a), and 1 mRNA (NOD2). Conclusions Our study identified 4 hub genes as potential inflammation-related biomarkers of SONFH. Moreover, we proposed a ceRNA network of lncRNAs targeting hsa-miR-320a, hsa-miR-320a, and NOD2 as a potential RNA regulatory pathway that controls disease progression in ONFH.
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Liu C, Liu X, Li X. PFKP and GPC6 Variants Were Correlated with Alcohol-Induced Femoral Head Necrosis Risk in the Chinese Han Population. Pharmgenomics Pers Med 2022; 15:797-808. [PMID: 36110408 PMCID: PMC9469939 DOI: 10.2147/pgpm.s369957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Accepted: 08/30/2022] [Indexed: 11/23/2022] Open
Abstract
Background Osteonecrosis of the femoral head (ONFH) is a common joint disease caused by excessive drinking, genetic factors, etc. The purpose of this study was to investigate the association between PFKP and GPC6 variants and alcohol-induced ONFH (AIONFH) risk in the Chinese Han population. Methods This study genotyped 9 selected single nucleotide polymorphisms (SNPs) in 402 males by Agena MassARRAY Assay. By calculating odds ratios (ORs) and 95% confidence intervals (CIs), we assessed the effect of gene polymorphisms on AIONFH occurrence. False-positive report probability (FPRP) analysis and power were also used to evaluate the significant results. Multifactor dimensionality reduction (MDR) software was also utilized to predict the association between the selected SNPs and AIONFH risk. Results The overall analysis showed that PFKP rs10903966 and GPC6 rs7320969 were correlated with AIONFH risk. GPC6 rs4773724 was associated with a reduced risk of AIONFH, while individuals with GPC6 rs9523981 CC genotype had a higher risk of AIONFH than individuals with the other genotypes among people under 42 years old. Based on stratified analysis of necrotic sites, rs7320969 was related to a decreased risk of AIONFH, while rs10903966 and rs9523981 were related to an increased risk of AIONFH. In addition, rs1008993 and rs7320969 were observed to be linked to AIONFH risk in patients at different clinical stages. Meanwhile, there were significant differences in TC, TG, platelet, ApoA1 and ApoB levels among subjects with different genotypes of rs1008993, rs9523981, rs7320969 and rs59624626. The results of MDR showed that rs11251720 and rs7320969 may play a synergistic role in predicting the risk of AIONFH. Conclusion PFKP rs10903966 and GPC6 rs9523981 were associated with an increased risk of AIONFH, while GPC6 (rs7320969 and rs4773724) were correlated with a decreased risk of AIONFH. This result will need further experiments to verify.
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Affiliation(s)
- Chang Liu
- Emergency Department, The Second Hospital of Tangshan, Tangshan, 063000, People’s Republic of China
- Correspondence: Chang Liu, Emergency Department, The Second Hospital of Tangshan, #21, Jianshe North Road, North District, Tangshan City, Hebei, 063000, People’s Republic of China, Tel +86-18633328305, Email
| | - Xuan Liu
- The Fourth Department of Orthopaedics, Tangshan Hongqiao Orthopaedic Hospital, Tangshan, 064100, People’s Republic of China
| | - Xiaolin Li
- The Fourth Department of Orthopaedics, Tangshan Hongqiao Orthopaedic Hospital, Tangshan, 064100, People’s Republic of China
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Lv B, Cheng Z, Yu Y, Chen Y, Gan W, Li S, Zhao K, Yang C, Zhang Y. Therapeutic perspectives of exosomes in glucocorticoid-induced osteoarthrosis. Front Surg 2022; 9:836367. [PMID: 36034358 PMCID: PMC9405187 DOI: 10.3389/fsurg.2022.836367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 07/08/2022] [Indexed: 11/17/2022] Open
Abstract
Exosomes are widely involved in a variety of physiological and pathological processes. These important roles are also hidden in the physiological processes related to bone. Chondrocytes, osteoblasts, synovial fibroblasts, and bone marrow mesenchymal stem cells produce and secrete exosomes, thereby affecting the biology process of target cells. Furthermore, in the primary pathogenesis of osteoarthrosis induced by steroid hormones, mainly involve glucocorticoid (GC), the exosomes have also widely participated. Therefore, exosomes may also play an important role in glucocorticoid-induced osteoarthrosis and serve as a promising treatment for early intervention of osteoarthrosis in addition to playing a regulatory role in malignant tumors. This review summarizes the previous results on this direction, systematically combs the role and therapeutic potential of exosomes in GC-induced osteoarthrosis, discusses the potential role of exosomes in the treatment and prevention of GC-induced osteoarthrosis, and reveals the current challenges we confronted.
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Affiliation(s)
- Bin Lv
- Correspondence: Yukun ZhangCao Yang Kangcheng Zhao Bin Lv
| | | | | | | | | | | | - Kangcheng Zhao
- Correspondence: Yukun ZhangCao Yang Kangcheng Zhao Bin Lv
| | - Cao Yang
- Correspondence: Yukun ZhangCao Yang Kangcheng Zhao Bin Lv
| | - Yukun Zhang
- Correspondence: Yukun ZhangCao Yang Kangcheng Zhao Bin Lv
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Lin T, Cai K, Yang P, WuRi S, Chen W, Deng P, Li Z, Chen Z, He W, Zhang Q, Wei Q. Composite indices of femoral neck strength predicts the collapse of steroid-associated osteonecrosis of the femoral head: a retrospective study. BMC Musculoskelet Disord 2022; 23:722. [PMID: 35902852 PMCID: PMC9330666 DOI: 10.1186/s12891-022-05622-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 05/30/2022] [Indexed: 11/10/2022] Open
Abstract
PURPOSES The purpose of this study was to investigate the predictive effect exerted by composite indices of femoral neck strength (compressive strength index (CSI), bending strength index (BSI) and impact strength index (ISI) on the femoral head collapse in steroid-associated ONFH patients. METHODS Nonoperative steroid-associated osteonecrosis of the femoral head (ONFH) patients from 2017 to 2019 were selected. The patients fell into the collapsed group and the non-collapsed group according to whether the femoral head collapsed. CSI, BSI and ISI were calculated. Moreover, bone turnover markers were measured. The statistical analysis was conducted on the predictive effects of composite indices of femoral neck strength and bone turnover index on ONFH collapse. RESULTS A total of 62 patients were included. The mean CSI, BSI and ISI were significantly lower in the collapsed group than those in the non-collapsed group (P < 0.05). CSI, ISI,t-P1NP and β-CTx were suggested as the protective risk factors for the femoral head collapse in ONFH patients. The ISI area under the curve values was 0. 878.The mean survival time of the hips of patients with ISI greater than 0.435 was greater (P < 0.05) than that of patients with ISI less than 0.435. CONCLUSION The composite indices of femoral neck strength can predict steroid-associated ONFH femoral head collapse more effectively than the bone turnover markers. The ISI value of 0.435 is a potential cut-off value, lower than this value can predict the early collapse of steroid-associated ONFH.
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Affiliation(s)
- Tianye Lin
- Joint Center, the Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China.,Guangdong Research Institute for Orthopedics & Traumatology of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Kaishen Cai
- The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Peng Yang
- Guangdong Research Institute for Orthopedics & Traumatology of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Shana WuRi
- Guangdong Research Institute for Orthopedics & Traumatology of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Weijian Chen
- Guangzhou Orthopedic Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Pan Deng
- Department of Joint Orthopaedic, Baoji Hospital of Traditional Chinese Medicine, Baoji, Shaanxi, 721000, China
| | - Ziqi Li
- Joint Center, the Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China.,Guangdong Research Institute for Orthopedics & Traumatology of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Zhenqiu Chen
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Wei He
- Joint Center, the Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China.,Guangdong Research Institute for Orthopedics & Traumatology of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Qingwen Zhang
- Joint Center, the Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China. .,Guangdong Research Institute for Orthopedics & Traumatology of Chinese Medicine, Guangzhou, Guangdong, 510405, China.
| | - Qiushi Wei
- Joint Center, the Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China. .,Guangdong Research Institute for Orthopedics & Traumatology of Chinese Medicine, Guangzhou, Guangdong, 510405, China.
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40
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Duan P, Wang H, Yi X, Zhang H, Chen H, Pan Z. C/EBPα regulates the fate of bone marrow mesenchymal stem cells and steroid-induced avascular necrosis of the femoral head by targeting the PPARγ signalling pathway. Stem Cell Res Ther 2022; 13:342. [PMID: 35883192 PMCID: PMC9327281 DOI: 10.1186/s13287-022-03027-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 07/02/2022] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND The imbalance of osteogenic/adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is closely related to steroid-induced avascular necrosis of the femoral head (SANFH). We aimed to investigate the epigenetic mechanism of intramedullary fat accumulation and continuous osteonecrosis after glucocorticoid (GC) withdrawal in SANFH. METHODS An SANFH model was established in SD rats, which received an intermittent high GC dose for the first 4 weeks followed by an additional 4 weeks without GC. We explored the synergistic effects and mechanisms of C/EBPα and PPARγ on the differentiation of BMSCs by lentivirus-mediated gene knockdown and overexpression assays. A chromatin immunoprecipitation assay was performed to identify epigenetic modification sites on PPARγ in vivo and in vitro. RESULTS In the SANFH model, intramedullary fat was significantly increased, and the transcription factors C/EBPα and PPARγ were upregulated simultaneously in the femoral head. In vitro, C/EBPα promoted adipogenic differentiation of BMSCs by targeting the PPARγ signalling pathway, while overexpression of C/EBPα significantly impaired osteogenic differentiation. Further studies demonstrated that histone H3K27 acetylation of PPARγ played an important role in the epigenetic mechanism underlying SANFH. C/EBPα upregulates the histone H3K27 acetylation level in the PPARγ promoter region by inhibiting HDAC1. Additionally, inhibiting the histone acetylation level of PPARγ effectively prevented adipogenic differentiation, thus slowing the progression of SANFH. CONCLUSIONS Our results demonstrate the molecular mechanism by which C/EBPα regulates PPARγ expression by acetylating histones and revealed the epigenetic phenomenon in SANFH for the first time.
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Affiliation(s)
- Ping Duan
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hanyu Wang
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Xinzeyu Yi
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hao Zhang
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Hui Chen
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
| | - Zhenyu Pan
- Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
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Vitamin B 2 Prevents Glucocorticoid-Caused Damage of Blood Vessels in Osteonecrosis of the Femoral Head. BIOMED RESEARCH INTERNATIONAL 2022; 2022:4006184. [PMID: 35845964 PMCID: PMC9279053 DOI: 10.1155/2022/4006184] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 04/25/2022] [Accepted: 05/10/2022] [Indexed: 12/19/2022]
Abstract
Osteonecrosis of the femoral head (ONFH) is a disorder that can cause collapse of the femoral head. The damage and dysfunction of femoral head microvascular endothelial cells are related to the pathogenesis of glucocorticoid-induced ONFH. Reports suggest that vitamin B2 can promote osteoblast differentiation and prevent low bone mineral density and prevent reperfusion oxidative injury. To explore the effect and possible molecular mechanism of vitamin B2 on the ONFH and Human Umbilical Vein Endothelial Cells (HUVECs), we performed a rat model of ONFH by dexamethasone. The rats were randomly divided into four groups: control group, vitamin B2 group, dexamethasone group, and dexamethasone combined with vitamin B2 treatment group. HUVECs were used to further prove the role and mechanism of vitamin B2 in vitro. In patients, according to immunohistochemical and qRT-PCR of the femoral head, the angiogenic capacity of the ONFH femoral head is compromised. In vivo, it showed that vitamin B2 could inhibit glucocorticoid-induced ONFH-like changes in rats by suppressing cell apoptosis, promoting the regeneration of blood vessels, and increasing bone mass. According to in vitro results, vitamin B2 could induce the migration of HUVECs, enhance the expression of angiogenesis-related factors, and inhibit glucocorticoid-induced apoptosis. The underlying mechanism may be that vitamin B2 activates the PI3K signaling pathway. Vitamin B2 alleviated dexamethasone-induced ONFH, and vitamin B2 could promote the proliferation and migration of HUVECs and inhibit their apoptosis by activating the PI3K/Akt signaling pathway. Vitamin B2 may be a potentially effective treatment for ONFH.
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Ma J, Sun Y, Zhou H, Li X, Bai Y, Liang C, Jia X, Zhang P, Yang L. Animal Models of Femur Head Necrosis for Tissue Engineering and Biomaterials Research. Tissue Eng Part C Methods 2022; 28:214-227. [PMID: 35442092 DOI: 10.1089/ten.tec.2022.0043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Femur head necrosis, also known as osteonecrosis of the femoral head (ONFH), is a widespread disabling pathology mostly affecting young and middle-aged population and one of the major causes of total hip arthroplasty in the elderly. Currently, there are limited number of different clinical or medication options for the treatment or the reversal of progressive ONFH, but their clinical outcomes are neither satisfactory nor consistent. In pursuit of more reliable therapeutic strategies for ONFH, including recently emerged tissue engineering and biomaterials approaches, in vivo animal models are extremely important for therapeutic efficacy evaluation and mechanistic exploration. Based on the better understanding of pathogenesis of ONFH, animal modeling method has evolved into three major routes, including steroid-, alcohol-, and injury/trauma-induced osteonecrosis, respectively. There is no consensus yet on a standardized ONFH animal model for tissue engineering and biomaterial research; therefore, appropriate animal modeling method should be carefully selected depending on research purposes and scientific hypotheses. In this work, mainstream types of ONFH animal model and their modeling techniques are summarized, showing both merits and demerits for each. In addition, current studies and experimental techniques of evaluating therapeutic efficacy on the treatment of ONFH using animal models are also summarized, along with discussions on future directions related to tissue engineering and biomaterial research. Impact statement Exploration of tissue engineering and biomaterial-based therapeutic strategy for the treatment of femur head necrosis is important since there are limited options available with satisfactory clinical outcomes. To promote the translation of these technologies from benchwork to bedside, animal model should be carefully selected to provide reliable results and clinical outcome prediction. Therefore, osteonecrosis of the femoral head animal modeling methods as well as associated tissue engineering and biomaterial research are overviewed and discussed in this work, as an attempt to provide guidance for model selection and optimization in tissue engineering and biomaterial translational studies.
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Affiliation(s)
- Jiali Ma
- School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People's Republic of China
| | - Yuting Sun
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China
| | - Huan Zhou
- School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People's Republic of China.,Center for Health Sciences and Engineering, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, People's Republic of China
| | - Xinle Li
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China
| | - Yanjie Bai
- School of Chemical Engineering, Hebei University of Technology, Tianjin, People's Republic of China
| | - Chunyong Liang
- School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People's Republic of China.,Changzhou Blon Minimally Invasive Medical Device Technology Co. Ltd., Jiangsu, People's Republic of China
| | - Xiaowei Jia
- School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People's Republic of China
| | - Ping Zhang
- Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People's Republic of China
| | - Lei Yang
- School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People's Republic of China.,Center for Health Sciences and Engineering, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, People's Republic of China
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Chen CY, Rao SS, Yue T, Tan YJ, Yin H, Chen LJ, Luo MJ, Wang Z, Wang YY, Hong CG, Qian YX, He ZH, Liu JH, Yang F, Huang FY, Tang SY, Xie H. Glucocorticoid-induced loss of beneficial gut bacterial extracellular vesicles is associated with the pathogenesis of osteonecrosis. SCIENCE ADVANCES 2022; 8:eabg8335. [PMID: 35417243 PMCID: PMC9007505 DOI: 10.1126/sciadv.abg8335] [Citation(s) in RCA: 81] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2021] [Accepted: 02/24/2022] [Indexed: 06/14/2023]
Abstract
Osteonecrosis of the femoral head (ONFH) commonly occurs after glucocorticoid (GC) therapy. The gut microbiota (GM) participates in regulating host health, and its composition can be altered by GC. Here, this study demonstrates that cohousing with healthy mice or colonization with GM from normal mice attenuates GC-induced ONFH. 16S rRNA gene sequencing shows that cohousing with healthy mice rescues the GC-induced reduction of gut Lactobacillus animalis. Oral supplementation of L. animalis mitigates GC-induced ONFH by increasing angiogenesis, augmenting osteogenesis, and reducing cell apoptosis. Extracellular vesicles from L. animalis (L. animalis-EVs) contain abundant functional proteins and can enter the femoral head to exert proangiogenic, pro-osteogenic, and antiapoptotic effects, while its abundance is reduced after exposure to GC. Our study suggests that the GM is involved in protecting the femoral head by transferring bacterial EVs, and that loss of L. animalis and its EVs is associated with the development of GC-induced ONFH.
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Affiliation(s)
- Chun-Yuan Chen
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Shan-Shan Rao
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Xiangya School of Nursing, Central South University, Changsha, Hunan 410013, China
| | - Tao Yue
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yi-Juan Tan
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Hao Yin
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Ling-Jiao Chen
- Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510220, China
| | - Ming-Jie Luo
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Xiangya School of Nursing, Central South University, Changsha, Hunan 410013, China
| | - Zun Wang
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Xiangya School of Nursing, Central South University, Changsha, Hunan 410013, China
| | - Yi-Yi Wang
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Chun-Gu Hong
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Yu-Xuan Qian
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Ze-Hui He
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Jiang-Hua Liu
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Fei Yang
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China
| | - Fei-Yu Huang
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China
| | - Si-Yuan Tang
- Xiangya School of Nursing, Central South University, Changsha, Hunan 410013, China
| | - Hui Xie
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Movement System Injury and Repair Research Center, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Department of Sports Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
- Hunan Key Laboratory of Organ Injury, Aging and Regenerative Medicine, Changsha, Hunan 410008, China
- Hunan Key Laboratory of Bone Joint Degeneration and Injury, Changsha, Hunan 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
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Xiong J, Niu Y, Liu W, Zeng F, Cheng JF, Chen SQ, Zeng XZ. Effect of L3MBTL3/PTPN9 polymorphisms on risk to alcohol-induced ONFH in Chinese Han population. Neurol Sci 2022; 43:2823-2830. [PMID: 34373992 DOI: 10.1007/s10072-021-05486-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 07/16/2021] [Indexed: 11/26/2022]
Abstract
PURPOSE Alcohol-induced osteonecrosis femoral head necrosis (ONFH) is a disease that seriously affects human health. Abnormal expression of L3MBTL3/PTPN9 gene can cause a variety of human diseases. The purpose of this study is to investigate the effect of L3MBTL3/PTPN9 gene polymorphism on the susceptibility of alcohol-induced ONFH in Chinese Han population. METHODS A total of 308 alcohol-induced ONFH patients and 425 healthy controls were enrolled in this case-control study. Alleles, genotypes, genetic models, haplotypes, and multifactor dimensionality reduction analyses (MDR) based on age-corrected by using odds ratio (OR) and 95% confidence interval (CI) were performed. RESULTS Our result revealed rs2068957 in the L3MBTL3 gene increased the risk of alcohol ONFH under the recessive model after correction. Besides, we also found that rs75393192 in the PTPN9 gene was a protective site in stratification over 40 years of age and stage. In stratified analysis of necrotic sites, we only found that rs2068957 was associated with increased susceptibility of alcohol-induced ONFH under the co-dominant model and recessive model. Haplotype "GC" in the block (rs76107647|rs10851882 in PTPN9 gene) significantly decreased the susceptibility of alcoholic ONFH. CONCLUSIONS Our results provide evidence that L3MBTL3/PTPN9 polymorphisms are associated with alcohol-induced ONFH risk in Chinese Han population.
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Affiliation(s)
- Jun Xiong
- Department of Orthopedic Trauma, the Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Haikou, 570311, Hainan Province, China
| | - Yi Niu
- Department of Emergency and Critical Care Medicine, the Haikou Orthopedic and Diabetes Hospital of Shanghai Sixth People's Hospital, No. 3, Changxiu Road, Haikou, 570300, Hainan Province, China
| | - Wei Liu
- Department of Orthopedic Trauma, the Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Haikou, 570311, Hainan Province, China
| | - Fan Zeng
- Department of Orthopedic Trauma, the Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Haikou, 570311, Hainan Province, China
| | - Jian-Fei Cheng
- Department of Orthopedic Trauma, the Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Haikou, 570311, Hainan Province, China
| | - Shi-Qiang Chen
- Department of Orthopedic Trauma, the Hainan Affiliated Hospital of Hainan Medical University, No. 19, Xiuhua Road, Haikou, 570311, Hainan Province, China
| | - Xiang-Zhou Zeng
- Department of Pharmacology, School of Basic Medicine and Life Science, the Hainan Medical University, No. 3, Xueyuan Road, Haikou, 571199, Hainan Province, China.
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Li F, Cao Z, Li K, Huang K, Yang C, Li Y, Zheng C, Ye Y, Zhou T, Peng H, Liu J, Wang C, Xie K, Tang Y, Wang L. Cryogenic 3D Printing of ß-TCP/PLGA Composite Scaffolds Incorporated With BpV (Pic) for Treating Early Avascular Necrosis of Femoral Head. Front Bioeng Biotechnol 2022; 9:748151. [PMID: 35118053 PMCID: PMC8804314 DOI: 10.3389/fbioe.2021.748151] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 12/06/2021] [Indexed: 01/26/2023] Open
Abstract
Avascular necrosis of femoral head (ANFH) is a disease that is characterized by structural changes and collapse of the femoral head. The exact causes of ANFH are not yet clear, but small advances in etiopathogenesis, diagnosis and treatment are achieved. In this study, ß-tricalcium phosphate/poly lactic-co-glycolic acid composite scaffolds incorporated with bisperoxovanadium [bpV (pic)] (bPTCP) was fabricated through cryogenic 3D printing and were utilized to treat rat models with early ANFH, which were constructed by alcohol gavage for 6 months. The physical properties of bPTCP scaffolds and in vitro bpV (pic) release from the scaffolds were assessed. It was found that the sustained release of bpV (pic) promoted osteogenic differentiation and inhibited adipose differentiation of bone marrow-derived mesenchymal stem cells. Micro-computed tomography scanning and histological analysis confirmed that the progression of ANFH in rats was notably alleviated in bPTCP scaffolds. Moreover, it was noted that the bPTCP scaffolds inhibited phosphatase and tensin homolog and activated the mechanistic target of rapamycin signaling. The autophagy induced by bPTCP scaffolds could partially prevent apoptosis, promote osteogenesis and angiogenesis, and hence eventually prevent the progression of ANFH, suggesting that the bPTCP scaffold are promising candidate to treat ANFH.
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Affiliation(s)
- Feng Li
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
- Youjiang Medical University for Nationalities, Baise, China
| | - Zhifu Cao
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
- Youjiang Medical University for Nationalities, Baise, China
| | - Kai Li
- The Third Affiliated Hospital of Southern Medical University, Guangzhou, China
| | - Ke Huang
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Chengliang Yang
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Ye Li
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
- Youjiang Medical University for Nationalities, Baise, China
| | - Chuanchuan Zheng
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
- Youjiang Medical University for Nationalities, Baise, China
| | - Yulu Ye
- Youjiang Medical University for Nationalities, Baise, China
| | - Tingjie Zhou
- Youjiang Medical University for Nationalities, Baise, China
| | - Haoqiang Peng
- Youjiang Medical University for Nationalities, Baise, China
| | - Jia Liu
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
- Youjiang Medical University for Nationalities, Baise, China
- Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Baise, China
- Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Baise, China
- *Correspondence: Jia Liu, ; Chong Wang, ; Yujin Tang,
| | - Chong Wang
- School of Mechanical Engineering, Dongguan University of Technology, Dongguan, China
- *Correspondence: Jia Liu, ; Chong Wang, ; Yujin Tang,
| | - Kegong Xie
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
| | - Yujin Tang
- Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China
- Youjiang Medical University for Nationalities, Baise, China
- Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Baise, China
- Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Baise, China
- *Correspondence: Jia Liu, ; Chong Wang, ; Yujin Tang,
| | - Liqiang Wang
- State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
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Liu W, Wang X, Chen J, Zeng F, Xiong J. The polymorphisms of MIR31HG gene is correlated with alcohol-induced osteonecrosis of the femoral head in Chinese Han male population. Front Endocrinol (Lausanne) 2022; 13:976165. [PMID: 36506078 PMCID: PMC9731210 DOI: 10.3389/fendo.2022.976165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 10/26/2022] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Alcoholic osteonecrosis of the femoral head (ONFH) is a multifaceted illness that seriously disturbs the patients' quality of life. The role of lncRNAs in alcoholic ONFH has attracted widespread attention in recent years. This study mainly explored whether MIR31HG polymorphism affects the risk of ONFH. METHODS There were 733 males (308 alcohol-induced ONFH patients and 425 healthy controls). Seven single nucleotide polymorphisms from MIR31HG were genotyped using the Agena MassARRAY platform. Odds ratio (OR) and 95% confidence intervals (CI) via logistic regression was applied to assess the contribution of MIR31HG variants to alcoholic ONFH susceptibility. RESULTS We found that rs10965059 was related to a lower risk of alcoholic ONFH in the overall, age, and necrotic sites analysis. Rs10965064 also showed a risk-reducing effect in the occurrence of alcoholic ONFH patients older than 40 years old. CONCLUSIONS We confirmed that MIR31HG variants have a significant correlation with the occurrence of alcoholic ONFH among the Chinese Han male population. our findings may provide new ideas for understanding the effect of MIR31HG on the prevention and diagnosis of alcoholic ONFH.
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Lu C, Qi H, Xu H, Hao Y, Yang Z, Yu W, Xu P. Global research trends of steroid-induced osteonecrosis of the femoral head: A 30-year bibliometric analysis. Front Endocrinol (Lausanne) 2022; 13:1027603. [PMID: 36325458 PMCID: PMC9618610 DOI: 10.3389/fendo.2022.1027603] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 10/03/2022] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE To explore the global research trends and hotspots of steroid-induced osteonecrosis of the femoral head (SONFH) through qualitative and quantitative analysis of bibliometrics. METHODS All publications on SONFH published from 1992 to 2021 were extracted from the Web of Science Core Collection database. CiteSpace was used for the visualization analysis of major countries, active institutions, productive authors, and the burst of keywords. VOSviewer was used for coupling analysis of countries/regions, institutions, and authors. Microsoft Excel 2017 was used for statistical analysis, drawing bar charts, pie charts, and cumulative area charts. The software of MapInfo was used to draw the distribution map of the publications. RESULTS A total of 780 publications were included for analyses. The most productive year was 2020 with 98 records. China was the most influential country with 494 publications, an H-index of 59, and total citations of 16820. The most prolific institution was Shanghai Jiaotong University in China with 53 publications and 998 citations. Clinical Orthopaedics and Related Research (IF = 4.755, 2021) was the most active journal with 26 articles. The hot keywords were "osteonecrosis", "avascular necrosis", "osteogenic differentiation", "proliferation", "PPAR gamma", "apoptosis", "oxidative stress", "genetic polymorphism" and "mesenchymal stem cells". The keywords like "proliferation", "PPAR gamma" and "genome-wide" have emerged in recent years. CONCLUSION The number of publications in SONFH has increased significantly in the last three decades. The pathologic mechanism of SONFH gathered most research interests. Genomics and cell molecular biology of SONFH are the research frontiers.
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Affiliation(s)
- Chao Lu
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Haodong Qi
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
- Graduate School, Shaanxi University of traditional Chinese Medicine, Xi’an, China
| | - Hanbo Xu
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
- Graduate School, Shaanxi University of traditional Chinese Medicine, Xi’an, China
| | - Yangquan Hao
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Zhi Yang
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
| | - Wenxing Yu
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
- *Correspondence: Peng Xu, ; Wenxing Yu,
| | - Peng Xu
- Department of Joint Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, China
- *Correspondence: Peng Xu, ; Wenxing Yu,
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He XM, He MC, Yang P, Zhang QW, Chen ZQ, He W, Wei QS. The Therapeutic Effect of Huo Xue Tong Luo Capsules in Association Research Circulation Osseous (ARCO) Stage II Osteonecrosis of the Femoral Head: A Clinical Study With an Average Follow-up Period of 7.95 Years. Front Pharmacol 2021; 12:773758. [PMID: 34899331 PMCID: PMC8652332 DOI: 10.3389/fphar.2021.773758] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 11/01/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Huo Xue Tong Luo (HXTL) capsules are an oral preparation that could relieve pain and ameliorate osteonecrosis in patients with asymptomatic osteonecrosis of femoral head (ONFH). We wanted to verify whether it could be a treatment option for ARCO stage II ONFH. Methods: A total of 44 patients (66 hips) with ARCO stage II ONFH were recruited from June 1996 to October 2013 (clinical trial registry number: ChiCTR-RPC-15006,290). HXTL capsules were given under a specific protocol, and the endpoint was set as femoral head collapse. The clinical indicators [including visual analog scale (VAS) and Harris Hip Score (HHS)] and radiological indicators [including Tonnis classification, ARCO stage, Japanese Investigation Committee (JIC) classification, lateral preserved angle (LPA), anterior preserved angle (APA), and combined preserved angle (CPA)] before and after treatment were compared. Kaplan–Meier survival analysis and Cox regression analysis were used to identify the risk factors associated with femoral head collapse. Result: Twenty-six males and 18 females with an average age of 38.3 ± 2.8 were followed for an average of 7.95 years. Forty-six of the 66 (69.7%) hips had no progression in pain or collapse, and patients exhibited a higher HHS (p < 0.05) after therapy. Twenty of the 66 (30.3%) hips progressed in Tonnis classification and ARCO stage, but only one of the 66 (1.5%) hips required total hip arthroplasty (THA). The Kaplan–Meier survivorship curve suggested that the survival rates were 96.97% at 5 years, 69.15% at 10 years, and 40.33% at 15 years. Patients with type A necrotic lesions on anteroposterior (AP) and frog-leg lateral (FLL) radiographs revealed 100% survival rates. Multivariate Cox regression analysis revealed that patients with an LPA ≤ 60.9 exhibited a 3.87 times higher risk of collapse of the femoral head [95% confidence interval (CI), 1.241–5.673] than did those patients with an LPA>60.9. Conclusion: HXTL capsules could be a treatment option for ARCO stage II ONFH, resulting in improved hip function and delayed progression to femoral head collapse, especially when the anterior and lateral portions of the femoral head were not affected. However, an LPA of less than 60.9° may be a risk factor for collapse of the femoral head. Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=10829, identifier ChiCTR-OPC-15007030
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Affiliation(s)
- Xiao-Ming He
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, China.,Joint Center, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Min-Cong He
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, China.,Joint Center, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Peng Yang
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, China.,Joint Center, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qing-Wen Zhang
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, China.,Joint Center, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zhen-Qiu Chen
- The Third Orthopaedic Region, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wei He
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, China.,Joint Center, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qiu-Shi Wei
- Guangdong Research Institute for Orthopedics and Traumatology of Chinese Medicine, Guangzhou, China.,Joint Center, The Third Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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Liu T, Cao Y, Han C, An F, Wang T, Sun M, Ma C, Dong Q, Wang J. Association of MIR17HG and MIR155HG gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern China. J Orthop Surg Res 2021; 16:673. [PMID: 34781979 PMCID: PMC8594148 DOI: 10.1186/s13018-021-02669-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 08/11/2021] [Indexed: 01/05/2023] Open
Abstract
Introduction Steroid-induced osteonecrosis of the femoral head (ONFH) is a disease of the bone. Metabolism and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China. Methods A total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH. Results In the codominant model, patients with the MIR17HG SNPs (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039); in the recessive model, patients with the MIR17HG SNP (rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and the MIR155HG SNPs (rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). In the MIR17HG SNP (rs75267932), patients with different genotypes had different levels of triglyceride (TG). The MIR155HG SNPs (rs77699734, rs1893650, and rs34904192) showed differences in triglyceride (TG), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) levels in patients with different genotypes. Conclusion Our results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.
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Affiliation(s)
- Tingting Liu
- Inner Mongolia Medical University, Hohhot, 010110, Jinshan Development Zone, China.,The Second Affiliated Hospital of Inner Mongolia Medical University, No. 1, Yingfang Road, Huhhot, 010030, Hui District, China
| | - Yuju Cao
- Zhengzhou Traditional Chinese Medicine (TCM) Traumatology Hospital, No.1266, First Street, Hanghai East Road, Zhengzhou, 450009, China
| | - Changxu Han
- The Second Affiliated Hospital of Inner Mongolia Medical University, No. 1, Yingfang Road, Huhhot, 010030, Hui District, China
| | - Feimeng An
- Inner Mongolia Autonomous Region Hospital of Traditional Chinese Medicine, No. 11, Xingcheng District, Hohhott, 010010, China
| | - Tiantian Wang
- Inner Mongolia Medical University, Hohhot, 010110, Jinshan Development Zone, China.,The Second Affiliated Hospital of Inner Mongolia Medical University, No. 1, Yingfang Road, Huhhot, 010030, Hui District, China
| | - Menghu Sun
- Inner Mongolia Medical University, Hohhot, 010110, Jinshan Development Zone, China.,The Second Affiliated Hospital of Inner Mongolia Medical University, No. 1, Yingfang Road, Huhhot, 010030, Hui District, China
| | - Chao Ma
- The Second Affiliated Hospital of Inner Mongolia Medical University, No. 1, Yingfang Road, Huhhot, 010030, Hui District, China
| | - Qiumei Dong
- College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot, 010110, Jinshan Development Zone, China.
| | - Jianzhong Wang
- The Second Affiliated Hospital of Inner Mongolia Medical University, No. 1, Yingfang Road, Huhhot, 010030, Hui District, China.
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Li Y, Xu Z, Chang S. Glucocorticoids induce osteonecrosis of the femoral head through the Hippo signaling pathway. Open Life Sci 2021; 16:1130-1140. [PMID: 34746414 PMCID: PMC8549681 DOI: 10.1515/biol-2021-0102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2020] [Revised: 07/16/2021] [Accepted: 07/28/2021] [Indexed: 11/15/2022] Open
Abstract
Osteonecrosis of the femoral head (ONFH) induced by glucocorticoids (GCs) has been considered to be associated with the dysfunction of bone marrow mesenchymal stem cells (BMSCs). Studies have reported that GCs can regulate the normal differentiation of BMSCs. However, the exact mechanism of this regulation remains unclear. In this study, we used methylprednisolone (MPS) to induce BMSCs, and then found that the Hippo signaling pathway was upregulated in a dose-dependent manner compared to that in the control group. In addition, the osteogenic ability of BMSCs was decreased, as evaluated by Alizarin Red S staining analysis and alkaline phosphatase activity assays, accompanied by the downregulated expression of Runx2, osteopontin, and osteocalcin. Additionally, the adipogenic capacity of BMSCs under the MPS conditions was increased, as identified by Oil Red O staining with upregulated triglyceride and PPARγ expression. Moreover, suppression by knockdown of MST1 was found to attenuate the Hippo signaling pathway and adipogenic differentiation, while enhancing osteogenic differentiation. In conclusion, our findings revealed that the Hippo signaling pathway was involved in GC-ONFH by affecting the osteogenic and adipogenic differentiation capacities of BMSCs. Our study could provide a basis for further investigation of the specific function of the Hippo pathway in ONFH.
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Affiliation(s)
- Yugang Li
- Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, No. 278 Baoguang Avenue, Xindu District, Chengdu 610500, Sichuan, People's Republic of China
| | - Zechuan Xu
- Department of Orthopedics, The Second Affiliated Hospital of Chengdu Medical College (Nuclear Industry 416 Hospital), Chengdu 610057, Sichuan, People's Republic of China
| | - Shan Chang
- Department of Orthopedics, The First Affiliated Hospital of Chengdu Medical College, No. 278 Baoguang Avenue, Xindu District, Chengdu 610500, Sichuan, People's Republic of China
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