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Hu Y, Yang Q, Zhang J, Peng Y, Guang Q, Li K. Methods to predict osteonecrosis of femoral head after femoral neck fracture: a systematic review of the literature. J Orthop Surg Res 2023; 18:377. [PMID: 37217998 DOI: 10.1186/s13018-023-03858-7] [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: 01/25/2023] [Accepted: 05/15/2023] [Indexed: 05/24/2023] Open
Abstract
BACKGROUND Femoral neck fracture (FNF) is a very common traumatic disorder and a major cause of blood supply disruption to the femoral head, which may lead to a severe long-term complication, osteonecrosis of femoral head (ONFH). Early prediction and evaluation of ONFH after FNF could facilitate early treatment and may prevent or reverse the development of ONFH. In this review paper, we will review all the prediction methods reported in the previous literature. METHODS Studies on the prediction of ONFH after FNF were included in PubMed and MEDLINE databases with articles published before October 2022. Further screening criteria were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This study highlights all the advantages and disadvantages of the prediction methods. RESULTS There were a total of 36 studies included, involving 11 methods to predict ONFH after FNF. Among radiographic imaging, superselective angiography could directly visualize the blood supply of the femoral head, but it is an invasive examination. As noninvasive detection methods, dynamic enhanced magnetic resonance imaging (MRI) and SPECT/CT are easy to operate, have a high sensitivity, and increase specificity. Though still at the early stage of development in clinical studies, micro-CT is a method of highly accurate quantification that can visualize femoral head intraosseous arteries. The prediction model relates to artificial intelligence and is easy to operate, but there is no consensus on the risk factors of ONFH. For the intraoperative methods, most of them are single studies and lack clinical evidence. CONCLUSION After reviewing all the prediction methods, we recommend using dynamic enhanced MRI or single photon emission computed tomography/computed tomography in combination with the intraoperative observation of bleeding from the holes of proximal cannulated screws to predict ONFH after FNF. Moreover, micro-CT is a promising imaging technique in clinical practice.
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Affiliation(s)
- Yi Hu
- Department of Orthopaedics, The First People's Hospital of Changde City, Changde, China
| | - Qin Yang
- Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, China
| | - Jun Zhang
- Department of Orthopaedics, The First People's Hospital of Changde City, Changde, China
| | - Yu Peng
- Department of Orthopaedics, The First People's Hospital of Changde City, Changde, China
| | - Qingqing Guang
- Department of Orthopaedics, The First People's Hospital of Changde City, Changde, China
| | - Kaihu Li
- Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, China.
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Rezaei A, Li Y, Turmaine M, Bertazzo S, Howard CA, Arnett TR, Shakib K, Jell G. Hypoxia mimetics restore bone biomineralisation in hyperglycaemic environments. Sci Rep 2022; 12:13944. [PMID: 35977987 PMCID: PMC9385857 DOI: 10.1038/s41598-022-18067-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 08/04/2022] [Indexed: 11/08/2022] Open
Abstract
Diabetic patients have an increased risk of fracture and an increased occurrence of impaired fracture healing. Diabetic and hyperglycaemic conditions have been shown to impair the cellular response to hypoxia, via an inhibited hypoxia inducible factor (HIF)-1α pathway. We investigated, using an in vitro hyperglycaemia bone tissue engineering model (and a multidisciplinary bone characterisation approach), the differing effects of glucose levels, hypoxia and chemicals known to stabilise HIF-1α (CoCl2 and DMOG) on bone formation. Hypoxia (1% O2) inhibited bone nodule formation and resulted in discrete biomineralisation as opposed to the mineralised extracellular collagen fibres found in normoxia (20% O2). Unlike hypoxia, the use of hypoxia mimetics did not prevent nodule formation in normal glucose level. Hyperglycaemic conditions (25 mM and 50 mM glucose) inhibited biomineralisation. Interestingly, both hypoxia mimetics (CoCl2 and DMOG) partly restored hyperglycaemia inhibited bone nodule formation. These results highlight the difference in osteoblast responses between hypoxia mimetics and actual hypoxia and suggests a role of HIF-1α stabilisation in bone biomineralisation that extends that of promoting neovascularisation, or other system effects associated with hypoxia and bone regeneration in vivo. This study demonstrates that targeting the HIF pathway may represent a promising strategy for bone regeneration in diabetic patients.
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Affiliation(s)
- Azadeh Rezaei
- Division of Surgery & Interventional Science, University College London, 9th Floor Royal Free Hospital, London, NW3 2QG, UK
| | - Yutong Li
- Division of Surgery & Interventional Science, University College London, 9th Floor Royal Free Hospital, London, NW3 2QG, UK
| | - Mark Turmaine
- Department of Cell & Developmental Biology, University College London, London, WC1E 6BT, UK
| | - Sergio Bertazzo
- Department of Medical Physics & Biomedical Engineering, University College London, London, WC1E 6BT, UK
| | - Christopher A Howard
- Department of Physics & Astronomy, University College London, London, WC1E 6BT, UK
| | - Timothy R Arnett
- Department of Cell & Developmental Biology, University College London, London, WC1E 6BT, UK
| | - Kaveh Shakib
- Division of Surgery & Interventional Science, University College London, 9th Floor Royal Free Hospital, London, NW3 2QG, UK.
| | - Gavin Jell
- Division of Surgery & Interventional Science, University College London, 9th Floor Royal Free Hospital, London, NW3 2QG, UK.
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Kondo T, Otsuka Y, Aoki H, Goto Y, Kawaguchi Y, Waguri-Nagaya Y, Miyazawa K, Goto S, Aoyama M. The Inducible Nitric Oxide Synthase Pathway Promotes Osteoclastogenesis under Hypoxic Culture Conditions. THE AMERICAN JOURNAL OF PATHOLOGY 2021; 191:2072-2079. [PMID: 34560064 DOI: 10.1016/j.ajpath.2021.08.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 08/09/2021] [Accepted: 08/31/2021] [Indexed: 11/25/2022]
Abstract
Bone homeostasis depends on the balance between bone resorption by osteoclasts (OCs) and bone formation by osteoblasts. Bone resorption can become excessive under various pathologic conditions, including rheumatoid arthritis. Previous studies have shown that OC formation is promoted under hypoxia. However, the precise mechanisms behind OC formation under hypoxia have not been elucidated. The present study investigated the role of inducible nitric oxide synthase (iNOS) in OC differentiation under hypoxia. Primary bone marrow cells obtained from mice were stimulated with receptor activator of NF-κB ligand and macrophage colony-stimulating factor to induce OC differentiation. The number of OCs increased in culture under hypoxia (oxygen concentration, 5%) compared with that under normoxia (oxygen concentration, 20%). iNOS gene and protein expression increased in culture under hypoxia. Addition of an iNOS inhibitor under hypoxic conditions suppressed osteoclastogenesis. Addition of a nitric oxide donor to the normoxic culture promoted osteoclastogenesis. Furthermore, insulin-like growth factor 2 expression was significantly altered in both iNOS inhibition experiments and nitric oxide donor experiments. These data might provide clues to therapies for excessive osteoclastogenesis under several hypoxic pathologic conditions, including rheumatoid arthritis.
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Affiliation(s)
- Takao Kondo
- Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan
| | - Yuto Otsuka
- Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan
| | - Hiromasa Aoki
- Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan
| | - Yoh Goto
- Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Yohei Kawaguchi
- Department of Glial Cell Biology, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan; Department of Orthopaedic Surgery, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan
| | - Yuko Waguri-Nagaya
- Department of Orthopaedic Surgery, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan
| | - Ken Miyazawa
- Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Shigemi Goto
- Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan
| | - Mineyoshi Aoyama
- Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, Nagoya, Japan.
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Xu H, Wang C, Liu C, Peng Z, Li J, Jin Y, Wang Y, Guo J, Zhu L. Cotransplantation of mesenchymal stem cells and endothelial progenitor cells for treating steroid-induced osteonecrosis of the femoral head. Stem Cells Transl Med 2021; 10:781-796. [PMID: 33438370 PMCID: PMC8046137 DOI: 10.1002/sctm.20-0346] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 11/14/2020] [Accepted: 12/06/2020] [Indexed: 11/20/2022] Open
Abstract
Steroid-induced osteonecrosis of the femoral head (ONFH) is characterized by decreased osteogenesis, angiogenesis, and increased adipogenesis. While bone tissue engineering has been widely investigated to treat ONFH, its therapeutic effects remain unsatisfactory. Therefore, further studies are required to determine optimal osteogenesis, angiogenesis and adipogenesis in the necrotic area of the femoral head. In our study, we developed a carboxymethyl chitosan/alginate/bone marrow mesenchymal stem cell/endothelial progenitor cell (CMC/ALG/BMSC/EPC) composite implant, and evaluated its ability to repair steroid-induced ONFH. Our in vitro studies showed that BMSC and EPC coculture displayed enhanced osteogenic and angiogenic differentiation. When compared with single BMSC cultures, adipogenic differentiation in coculture systems was reduced. We also fabricated a three-dimensional (3D) CMC/ALG scaffold for loading cells, using a lyophilization approach, and confirmed its good cell compatibility characteristics, that is, high porosity, low cytotoxicity and favorable cell adhesion. 3D coculture of BMSCs and EPCs also promoted secretion of osteogenic and angiogenic factors. Then, we established an rabbit model of steroid-induced ONFH. The CMC/ALG/BMSC/EPC composite implant was transplanted into the bone tunnel of the rabbit femoral head after core decompression (CD) surgery. Twelve weeks later, radiographical and histological analyses revealed CMC/ALG/BMSC/EPC composite implants had facilitated the repair of steroid-induced ONFH, by promoting osteogenesis and angiogenesis, and reducing adipogenesis when compared with CD, CMC/ALG, CMC/ALG/BMSC and CMC/ALG/EPC groups. Thus, our data show that cotransplantation of BMSCs and EPCs in 3D scaffolds is beneficial in treating steroid-induced ONFH.
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Affiliation(s)
- Haixia Xu
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
| | - Chengqiang Wang
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
| | - Chun Liu
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
| | - Ziyue Peng
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
| | - Jianjun Li
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
| | - Yanglei Jin
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
| | - Yihan Wang
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
| | - Jiasong Guo
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
- Department of Histology and EmbryologySouthern Medical UniversityGuangzhouPeople's Republic of China
- Key Laboratory of Tissue Construction and Detection of Guangdong ProvinceGuangzhouPeople's Republic of China
- Institute of Bone BiologyAcademy of Orthopaedics, Guangdong ProvinceGuangzhouPeople's Republic of China
| | - Lixin Zhu
- Department of Spinal Surgery, Orthopedic Medical CenterZhujiang Hospital, Southern Medical UniversityGuangzhouPeople's Republic of China
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Non-operative predictors for subsequent interventions after intracapsular femoral neck fractures in elderly: A comprehensive analysis of the Hungarian nationwide health insurance database. Injury 2021; 52 Suppl 1:S31-S36. [PMID: 32067768 DOI: 10.1016/j.injury.2020.02.055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 02/09/2020] [Indexed: 02/02/2023]
Abstract
OBJECTIVES To investigate the correlation between non-operative prognostic factors and non-prosthetic fracture-related treatments following internal fixation of intracapsular femoral neck fractures in elderly patients. DESIGN AND SETTING Retrospective observational cohort study. Comprehensive analysis of the Hungarian nationwide health insurance database. PARTICIPANTS Data of in-patient records with S7200 ICD-10 codes were collected from the Hungarian National Health Insurance Fund Administration (HNHIFA) and from the health care provider institutes. The patients with femoral neck fractures in the year of 2000, following reduction and internal fixation aged 60 years or older were evaluated. The secondary, non-prosthetic fracture related treatments during the 8 year follow-up period were registered. MAIN OUTCOME MEASURES Of the prognostic factors, age, gender, type of fracture, season and day of the primary surgery, length of waiting time to the operation and the accompanied diseases were evaluated as risk factors for all type of fracture-related further interventions, with the exception of arthroplasties. RESULTS A total of 2895 patients with intracapsular femoral neck fractures met the study criteria. The mean age was 77.96 years (SD: 8.54). The cohort of the patients was observed for a total of 10,077.8 person-years. The non-prosthetic fracture related treatment was performed in 265 patients (9,2%); the median of the time elapsed to the secondary definitive treatment was 3.5 months. With Cox regression analysis, significant correlation was revealed between the incidence of non-prosthetic treatment and younger age (year, HR = 0.977, p = 0.002), surgical delay (12-24 h vs 0-6 h, HR = 1.518, p = 0.023; 24h+ vs 0-6 h, HR = 1.372, p = 0.050), season of primary osteosynthesis (fall vs summer, HR = 0.636, p = 0.012), and type of femoral neck fracture (intracapsular displaced vs intracapsular undisplaced, HR = 1.340, p = 0,047). There was no significant effect of the day of primary surgery, the gender and the presence of co-morbidities on the incidence of further surgical interventions. CONCLUSION The summertime primary surgical intervention, delay of surgery longer than 12 h and type of femoral neck fracture are independent predictors of non-prosthetic further treatment of femoral neck fractures in elderly patients. LEVEL OF EVIDENCE Level IV, evidence from cohort studies.
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Noh JH, Lee JY, Hwang S, Lee KH. Prediction of femoral head avascular necrosis following femoral neck fracture: "pin-tract sign" of 99mTc-HDP pinhole bone scan after metallic fixation. Hip Int 2020; 30:641-648. [PMID: 31280602 PMCID: PMC7406965 DOI: 10.1177/1120700019860492] [Citation(s) in RCA: 4] [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] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate the predicting value of 99mTc-hydroxydiphosphonate (HDP) pinhole bone scan in development of osteonecrosis of femoral head (ONFH) in patients with femoral neck fracture after cannulated screw fixation. METHODS Pinhole bone scan of patients with metallically fixed femoral neck fracture from 2001 to 2015 were retrospectively reviewed. Initial pinhole bone scan was obtained within 2-3 weeks after surgery. Findings of initial pinhole bone scan were divided in to 4 groups. Group CU included cold defect in affected femoral head, group HU with no cold defect. Group PP with increased uptake along the inserted screws and group PN with no increased uptake along the inserted screws. More than 6 months of follow-up with pinhole bone scan and clinico-radiological evidence for ONFH was reviewed. RESULTS 72 patients (mean age 54.01 years, male 22, female 50) were included. 19 patients were in group CU, 53 in group HU. 60 patients were in group PP, 12 in group PN. During the follow-up, 13 patients were diagnosed as ONFH. 9 (47.36%) patients in group CU developed ONFH and 4 (7.5%) in group HU. 4 (6.66%) patients in group PP developed ONFH and 9 (75%) in group PN. CONCLUSIONS To predict ONFH of femoral head followed by neck fracture, many imaging techniques with variable results were known. In this study, cold defect in early postoperative pinhole bone scans could predict ONFH, and loss of increased uptake along screw inserted site could be a strong indicative sign of ONFH. Further evaluation with a larger population is necessary.
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Affiliation(s)
| | | | | | - Kee Haeng Lee
- Kee Haeng Lee, Department of Orthopaedic Surgery, The Catholic University of Korea, Bucheon St. Mary’s Hospital, 327 Sosa-ro, Wonmi-gu, Bucheon, 14647, Republic of Korea.
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Liu GZ, Chen C, Kong N, Tian R, Li YY, Li Z, Wang KZ, Yang P. Identification of potential miRNA biomarkers for traumatic osteonecrosis of femoral head. J Cell Physiol 2020; 235:8129-8140. [PMID: 31951022 DOI: 10.1002/jcp.29467] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Accepted: 01/07/2020] [Indexed: 12/13/2022]
Abstract
Traumatic osteonecrosis of femoral head (TONFH) is a common orthopedic disease caused by physical injury in hip. However, the unclear pathogenesis mechanism of TONFH and lacking of simple noninvasive early diagnosis method cause the necessity of hip replacement for most patients with TONFH. In this study, we aimed to identify circulating microRNAs (miRNAs) by integrated bioinformatics analyses as potential biomarker of TONFH. mRNA expression profiles were downloaded from the Gene Expression Omnibus database. Then we combined two miRNA screen methods: Weighted gene co-expression network analysis and fold change based differentially expressed miRNAs analysis. As a result, we identified 14 key miRNAs as potential biomarkers for TONFH. Besides, 302 target genes of these miRNAs were obtained and the miRNA-mRNA interaction network was constructed. Furthermore, the results of Kyoto Encyclopedia of Gene and Genome pathway analysis, Gene Ontology function analysis, protein-protein interaction (PPI) network analysis and PPI network module analysis showed close correlation between these 14 key miRNAs and TONFH. Then we established receiver operating characteristic curves and identified 6-miRNA signature with highly diagnosis value including miR-93-5p (area under the curve [AUC] = 0.93), miR-1324 (AUC = 0.92), miR-4666a-3p (AUC = 0.92), miR-5011-3p (AUC = 0.92), and miR-320a (AUC = 0.89), miR-185-5p (AUC = 0.89). Finally, the results of quantitative real-time polymerase chain reaction confirmed the significantly higher expression of miR-93-5p and miR-320a in the serum of patients with ONFH. These circulating miRNAs could serve as candidate early diagnosis markers and potential treatment targets of TONFH.
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Affiliation(s)
- Guan-Zhi Liu
- Bone and Joint Surgery Center, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Chen Chen
- Department of Cardiovascular Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Ning Kong
- Bone and Joint Surgery Center, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Run Tian
- Bone and Joint Surgery Center, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Yi-Yang Li
- Bone and Joint Surgery Center, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhe Li
- Bone and Joint Surgery Center, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Kun-Zheng Wang
- Bone and Joint Surgery Center, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Pei Yang
- Bone and Joint Surgery Center, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
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Li G, Jin D, Shao X, Liu Z, Duan J, Akileh R, Cao S, Liu T. Effect of cannulated screws with deep circumflex iliac artery-bone grafting in the treatment of femoral neck fracture in young adults. Injury 2018; 49:1587-1593. [PMID: 29929779 DOI: 10.1016/j.injury.2018.06.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 06/11/2018] [Indexed: 02/02/2023]
Abstract
OBJECTIVES Surgical treatment of femoral neck fracture in young adults is clinically challenging due to the high incidence of avascular necrosis of femoral head and fracture nonunion. The objective of this study is to evaluate the effectiveness of cannulated screws with deep circumflex iliac artery bone grafting (DCIABG) by comparing to the routinely used method in the treatment of femoral neck fracture in young adults. METHODS From March 2006 to December 2012, a total of 185 patients with femoral neck fracture were admitted to the hospital for internal fixation surgery, 103 patients (61 males and 42 females, mean age of 39.1 years) were treated with three cannulated screws with DCIABG (group A), and 82 patients (49 males and 33 females, mean age of 35.5 years) were treated with three cannulated screws without DCIABG (group B). RESULTS All patients were followed up for at least 24 months after the surgery. The patients in group A had a significantly higher Harris Hip Score (p < 0.001), shorter fracture healing time (p < 0.001), lower occurrence rate of avascular necrosis of femoral head (p = 0.008) and fracture nonunion (p = 0.012) compared to the patients in group B. However, the operation time and intraoperative blood loss were significantly lower in patients in group B than those in group A (p < 0.001). CONCLUSIONS Cannulated screws with DCIABG significantly reduced femoral head osteonecrosis and fracture nonunion. Therefore, it is a feasible and effective method in the treatment of young adult patients with femoral neck fracture.
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Affiliation(s)
- Guanghui Li
- Department of Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, 510630, China; Department of Orthopedic Surgery, The First Traditional Chinese Medical Hospital of Hunan Changde, Changde, Hunan, 415000, China
| | - Dadi Jin
- Department of Orthopedic Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, 510630, China.
| | - Xianfang Shao
- Department of Orthopedic Surgery, The First Traditional Chinese Medical Hospital of Hunan Changde, Changde, Hunan, 415000, China
| | - Zhijun Liu
- Department of Orthopedic Surgery, The First Traditional Chinese Medical Hospital of Hunan Changde, Changde, Hunan, 415000, China
| | - Jianhui Duan
- Department of Orthopedic Surgery, The First Traditional Chinese Medical Hospital of Hunan Changde, Changde, Hunan, 415000, China
| | - Raji Akileh
- Department of Biomedical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, WV, 24901, United States
| | - Shousong Cao
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, 646000, China
| | - Tuoen Liu
- Department of Biomedical Sciences, West Virginia School of Osteopathic Medicine, Lewisburg, WV, 24901, United States.
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Fan W, Zhu L, Chen J, Guo C, Yan Z. Identifying Patients Who Will Most Benefit from Single Photon Emission Computerized Tomography and Computerized Tomography After Femoral Neck Fracture. Med Sci Monit 2017; 23:5669-5674. [PMID: 29182595 PMCID: PMC5717992 DOI: 10.12659/msm.904026] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 06/07/2017] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND Single photon emission computerized tomography and computerized tomography (SPECT/CT) is useful for assessing blood supply within the femoral head after femoral neck fracture, but its use in all femoral neck fracture patients is not feasible. Therefore, the present study aimed to identify the patients for whom SPECT/CT examination will be most beneficial. MATERIAL AND METHODS Sixty-five patients with a unilateral femoral neck fracture who underwent SPECT/CT examination of the hip and were treated via closed reduction and internal fixation with three screws were enrolled between January 2009 and March 2011. A decision tree model (C 5.0) was used to identify the factors that best reflect blood supply and to build a flowchart for identifying patients who would benefit from SPECT/CT. RESULTS Fracture type was most strongly associated with the Fracture/Normal (F/N) ratio, which reflects the blood supply to the fractured femoral head. Age and the time interval from injury to examination were also associated with the F/N ratio. SPECT/CT examination is most beneficial for patients with a displaced fracture, especially if they are over 58 years old and the time interval from injury to examination is less than 10 days. CONCLUSIONS Our results indicate that elderly people with a displaced fracture are most likely to benefit from SPECT/CT examination, which can show the blood supply to the femoral head within a relatively short window of time after the injury.
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Affiliation(s)
| | | | | | | | - Zuoqin Yan
- Corresponding Author: Zuoqin Yan, e-mail:
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Lazaro LE, Dyke JP, Thacher RR, Nguyen JT, Helfet DL, Potter HG, Lorich DG. Focal osteonecrosis in the femoral head following stable anatomic fixation of displaced femoral neck fractures. Arch Orthop Trauma Surg 2017; 137:1529-1538. [PMID: 28849268 DOI: 10.1007/s00402-017-2778-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2017] [Indexed: 12/22/2022]
Abstract
INTRODUCTION Femoral head (FH) osteonecrosis (ON) and subsequent segmental collapse is a major concern following displaced femoral neck fractures (FNF). We aimed to quantify residual perfusion to the FH following FNF and evaluate the viability of the FH overtime after surgical fixation. MATERIALS AND METHODS Twenty-three patients with FNF underwent dynamic contrast-enhanced (DCE)-MRI to estimate bone perfusion in the FH, using the contralateral side as control. Following open anatomic reduction and a length/angle-stable fixation, a special MRI sequence evaluated the FH for ON changes over time at 3 and 12 months after surgery. RESULTS We found significant compromise of both arterial inflow [83.1%-initial area under the curve (IAUC) and 73.8%-peak) and venous outflow (243.2%-elimination rate (K el)] in the FH of the fractured side. The supero-medial quadrant suffered the greatest decrease in arterial inflow with a significant decrease of 71.6% (IAUC) and 68.5% (peak). Post-operative MRI revealed a high rate (87%-20/23) of small ON segments within the FH, and all developed in the anterior aspect of the supero-medial quadrants. Fracture characteristics, including subcapital FNF, varus deformity, posterior roll-off ≥20° and Pauwel's angle of 30°-50° demonstrated a greater decrease in perfusion compared to contralateral controls. CONCLUSION FNF significantly impaired the vascular supply to the FH, resulting in high incidence of small ON segments in the supero-medial quadrant of the FH. However, maintained perfusion, probably through the inferior retinacular system, coupled with urgent open anatomic reduction and stable fixation resulted in excellent clinical and radiographic outcomes despite a high rate of small ON segments noted on MRI. LEVEL OF EVIDENCE Level I: Prognostic Investigation.
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Affiliation(s)
- Lionel E Lazaro
- Hospital for Special Surgery and New York Presbyterian Hospital, 535 East 70th Street, New York, NY, USA. .,Weill Medical College of Cornell University, New York, NY, USA. .,Orthopaedic Trauma Service, New York, USA.
| | - Jonathan P Dyke
- Citigroup Biomedical Imaging Center, Weill Medical College of Cornell University, New York, NY, USA
| | - Ryan R Thacher
- Hospital for Special Surgery and New York Presbyterian Hospital, 535 East 70th Street, New York, NY, USA.,Weill Medical College of Cornell University, New York, NY, USA.,Orthopaedic Trauma Service, New York, USA
| | - Joseph T Nguyen
- Departments of Epidemiology and Biostatistics Core, Hospital for Special Surgery, New York, NY, USA
| | - David L Helfet
- Hospital for Special Surgery and New York Presbyterian Hospital, 535 East 70th Street, New York, NY, USA.,Weill Medical College of Cornell University, New York, NY, USA.,Orthopaedic Trauma Service, New York, USA
| | - Hollis G Potter
- Department of Radiology and Imaging, Hospital for Special Surgery and Weill Medical College of Cornell University, New York, NY, USA
| | - Dean G Lorich
- Hospital for Special Surgery and New York Presbyterian Hospital, 535 East 70th Street, New York, NY, USA.,Weill Medical College of Cornell University, New York, NY, USA.,Orthopaedic Trauma Service, New York, USA
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Regulation of Osteogenic Differentiation of Placental-Derived Mesenchymal Stem Cells by Insulin-Like Growth Factors and Low Oxygen Tension. Stem Cells Int 2017; 2017:4576327. [PMID: 29138637 PMCID: PMC5613461 DOI: 10.1155/2017/4576327] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Accepted: 07/20/2017] [Indexed: 01/20/2023] Open
Abstract
Placental mesenchymal stem cells (PMSCs) are multipotent cells that can differentiate in vitro to multiple lineages, including bone. Insulin-like growth factors (IGFs, IGF-1 and IGF-2) participate in maintaining growth, survival, and differentiation of many stem cells, including osteoprogenitors. Low oxygen tension (PO2) can maintain stem cell multipotency and impede osteogenic differentiation. In this study, we investigated whether PMSC osteogenic differentiation is influenced by low PO2 and by IGFs. Our results indicated that low PO2 decreased osteogenic markers RUNX2 and OPN; however, re-exposure to higher oxygen tension (room air) restored differentiation. IGFs, especially IGF-1, triggered an earlier expression of RUNX2 and enhanced OPN and mineralization. RUNX2 was phosphorylated in room air and augmented by IGFs. IGF-1 receptor (IGF-1R) was increased in low PO2 and reduced by IGFs, while insulin receptor (IR) was increased in differentiating PMSCs and enhanced by IGF-1. Low PO2 and IGFs maintained higher IR-A which was switched to IR-B in room air. PI3K/AKT was required for osteogenic differentiation, while MEK/ERK was required to repress an RUNX2 and OPN increase in low PO2. Therefore, IGFs, specifically IGF-1, trigger the earlier onset of osteogenic differentiation in room air, whereas, reversibly, low PO2 impedes complete differentiation by maintaining higher multipotency and lower differentiation markers.
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12
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Chen L, Hong G, Fang B, Zhou G, Han X, Guan T, He W. Predicting the collapse of the femoral head due to osteonecrosis: From basic methods to application prospects. J Orthop Translat 2017; 11:62-72. [PMID: 29662770 PMCID: PMC5866406 DOI: 10.1016/j.jot.2016.11.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 09/28/2016] [Accepted: 11/10/2016] [Indexed: 12/25/2022] Open
Abstract
Collapse of the femoral head is the most significant pathogenic complication arising from osteonecrosis of the femoral head. It is related to the disruption of the maintenance of cartilage and bone, and results in an impaired function of the vascular component. A method for predicting the collapse of the femoral head can be treated as a type of clinical index. Efforts in recent years to predict the collapse of the femoral head due to osteonecrosis include multiple methods of radiographic analysis, stress distribution analysis, finite element analysis, and other innovative methods. Prediction methods for osteonecrosis of the femoral head complications originated in Western countries and have been further developed in Asia. Presently, an increasing number of surgeons have chosen to focus on surgical treatments instead of prediction methods to guide more conservative interventions, resulting in a growing reliance on the more prevalent and highly effective total hip arthroplasty, rather than on more conservative treatments. In this review, we performed a literature search of PubMed and Embase using search terms including "osteonecrosis of femoral head," "prediction," "collapse," "finite element," "radiographic images," and "stress analysis," exploring the basic prediction method and prospects for new applications.
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Affiliation(s)
- Leilei Chen
- Guangzhou University of Chinese Medicine, The National Key Discipline and The Orthopedic Laboratory, Guangzhou, Guangdong, PR China.,Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China
| | - GuoJu Hong
- Guangzhou University of Chinese Medicine, The National Key Discipline and The Orthopedic Laboratory, Guangzhou, Guangdong, PR China.,Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China.,School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA, Australia
| | - Bin Fang
- Guangzhou University of Chinese Medicine, The National Key Discipline and The Orthopedic Laboratory, Guangzhou, Guangdong, PR China.,Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China
| | - Guangquan Zhou
- Guangzhou University of Chinese Medicine, The National Key Discipline and The Orthopedic Laboratory, Guangzhou, Guangdong, PR China.,Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China
| | - Xiaorui Han
- Guangzhou University of Chinese Medicine, The National Key Discipline and The Orthopedic Laboratory, Guangzhou, Guangdong, PR China.,Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China
| | - Tianan Guan
- Guangzhou University of Chinese Medicine, The National Key Discipline and The Orthopedic Laboratory, Guangzhou, Guangdong, PR China.,Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China
| | - Wei He
- Guangzhou University of Chinese Medicine, The National Key Discipline and The Orthopedic Laboratory, Guangzhou, Guangdong, PR China.,Department of Orthopedics, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, PR China
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Chen J, Chen L, Chang CC, Zhang Z, Li W, Swain MV, Li Q. Micro-CT based modelling for characterising injection-moulded porous titanium implants. INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN BIOMEDICAL ENGINEERING 2017; 33. [PMID: 26916052 DOI: 10.1002/cnm.2779] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Revised: 02/15/2016] [Accepted: 02/21/2016] [Indexed: 06/05/2023]
Abstract
Design of prosthetic implants to ensure rapid and stable osseointegration remains a significant challenge, and continuous efforts have been directed to new implant materials, structures and morphology. This paper aims to develop and characterise a porous titanium dental implant fabricated by metallic powder injection-moulding. The surface morphology of the specimens was first examined with a scanning electron microscope (SEM), followed by microscopic computerised tomography (μ-CT) scanning to capture its 3D microscopic features non-destructively. The nature of porosity and pore sizes were determined statistically. A homogenisation technique based on the Hills-energy theorem was adopted to evaluate its directional elastic moduli, and the conservation of mass theorem was employed to quantify the oxygen diffusivity for bio-transportation feature. This porous medium was found to have pore sizes varying from 50 to 400 µm and the average porosity of 46.90 ± 1.83%. The anisotropic principal elastic moduli were found fairly close to the upper range of cortical bone, and the directional diffusivities could potentially enable radial osseous tissue ingrowth and vascularisation. This porous titanium successfully reduces the elastic modulus mismatch between implant and bone for dental and orthopaedic applications, and provides improved capacity for transporting oxygen, nutrient and waste for pre-vascular network formation. Copyright © 2016 John Wiley & Sons, Ltd.
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Affiliation(s)
- Junning Chen
- School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, NSW, 2006, Australia
| | - Liangjian Chen
- State Key Laboratory of Powder Metallurgy, Central South University, Changsha, 410083, People's Republic of China
| | - Che-Cheng Chang
- School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, NSW, 2006, Australia
| | - Zhongpu Zhang
- School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, NSW, 2006, Australia
| | - Wei Li
- School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, NSW, 2006, Australia
| | - Michael V Swain
- Faculty of Dentistry, The University of Sydney, NSW, 2006, Australia
| | - Qing Li
- School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, NSW, 2006, Australia
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14
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Dargan DP, Callachand F, Diamond OJ, Connolly CK. Three-year outcomes of intracapsular femoral neck fractures fixed with sliding hip screws in adults aged under sixty-five years. Injury 2016; 47:2495-2500. [PMID: 27637999 DOI: 10.1016/j.injury.2016.09.013] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2016] [Revised: 08/14/2016] [Accepted: 09/06/2016] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Intracapsular femoral neck fractures remain associated with high rates of post-traumatic femoral head necrosis, non-union, and revision surgery. AIM Our aim was to identify factors associated with revision surgery in intracapsular femoral neck fractures treated with sliding hip screws (SHS) in adults aged <65 years. PATIENTS AND METHODS Consecutive admissions were identified retrospectively from the Royal Victoria Hospital, Belfast, which was the largest volume hospital on the National Hip Fracture Database. Of 2201 hip fractures between 1st August 2008 and 31st December 2010, 97 (4%) intracapsular fractures treated with SHS in adults <65 years were followed for a mean of 2.9 years (range 0-6.6). RESULTS Twenty-one (22%) hips were revised to arthroplasty. Avascular necrosis developed in 28 (29%) femoral heads. Eight (8%) fractures proceeded to non-union. Displaced fractures (p<0.001, Fisher's exact [FE]), posterior comminution (p=0.049, FE), chronic respiratory disease (p=0.006, FE) and residual distraction (p=0.011, χ2) were associated with revision to arthroplasty. Multiple regression found displaced fractures (p=0.006) and chronic respiratory disease (p=0.017) significant; in the latter 4 of 6 were revised (67%), including all four patients with chronic obstructive pulmonary disease (COPD). Eleven (11%) individuals required walking aids before injury, which rose to 34 (35%) at one year (p<0.0001, χ2). Eighty-nine (92%) individuals could walk alone outdoors before injury, but only 76 (78%) at one year (p=0.009, χ2). CONCLUSIONS Displaced fractures in individuals with chronic respiratory disease should be considered high risk for revision to arthroplasty. Posterior cortex deficiency should be evaluated prior to choice of operation. Fracture biology and revascularisation play a greater role than operation timing. A significant proportion of individuals do not recovery pre-morbid mobility by one year.
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Affiliation(s)
- D P Dargan
- Department of Trauma and Orthopaedics, Royal Victoria Hospital, Belfast, BT12 6BA, Northern Ireland.
| | - F Callachand
- Department of Trauma and Orthopaedics, Royal Victoria Hospital, Belfast, BT12 6BA, Northern Ireland
| | - O J Diamond
- Department of Trauma and Orthopaedics, Royal Victoria Hospital, Belfast, BT12 6BA, Northern Ireland
| | - C K Connolly
- Department of Trauma and Orthopaedics, Royal Victoria Hospital, Belfast, BT12 6BA, Northern Ireland
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Abstract
OBJECTIVES Avascular necrosis (AVN) of the femoral head is a devastating complication following fixation of femoral neck fractures in younger adults. In this study, we investigate the prognostic utility of disuse osteopenia. DESIGN Retrospective study. SETTING Three academic Level 1 trauma centers. PATIENTS One hundred twenty patients younger than 60 years treated for a femoral neck fracture. INTERVENTION N/A. MAIN OUTCOME MEASURES The presence of sclerosis or osteopenia, compared to the contralateral femoral head, was measured 6 weeks from injury both subjectively and using a novel radiographic measure, the relative density ratio (RDR). The outcome measure was radiographic development of AVN. RESULTS The presence of relative sclerosis was associated with AVN and overall treatment failure. Patients with subjective relative sclerosis had a 12.6 (95% confidence interval, 2.9-61.3; P < 0.001) times higher odds of developing AVN. Multiple logistic regression showed that for every 0.10 increase in the RDR, there was a 5.2 increase in the odds (95% confidence interval, 2.1-26.9; P = 0.009) of developing AVN. Patients with an RDR of ≥1.2 have an 80% probability of AVN, whereas those with an RDR ≤0.8 have a <1% probability of developing AVN. CONCLUSIONS Disuse osteopenia detected on 6-week radiographs is a favorable prognostic sign following fixation of femoral neck fractures. Patients who have relative sclerosis of the femoral head at 6-week follow-up are at a higher risk of developing AVN. LEVEL OF EVIDENCE Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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Wang T, Sun JY, Zha GC, Jiang T, You ZJ, Yuan DJ. Analysis of risk factors for femoral head necrosis after internal fixation in femoral neck fractures. Orthopedics 2014; 37:e1117-23. [PMID: 25437087 DOI: 10.3928/01477447-20141124-60] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Accepted: 03/25/2014] [Indexed: 02/03/2023]
Abstract
Femoral head necrosis is a rare but devastating complication following femoral neck fracture. The reported incidence of avascular necrosis after femoral neck fracture fixation varies widely, and there is no consensus regarding its risk factors. The aim of this study was to analyze the risk factors for femoral head necrosis after internal fixation in femoral neck fracture. This retrospective study included 166 patients with femoral neck fractures treated with surgical reduction and internal fixation at the authors' institution from January 2004 to December 2008. Eight patients died for reasons unrelated to the surgery, and 12 patients were lost to follow-up. The remaining 146 patients (146 fractures) were followed until union or until conversion to total hip arthroplasty. The patients included 61 males and 85 females with an average age of 47.5 years (range, 18-68 years). The authors analyzed the following factors: age, sex, Garden classification, reduction quality, surgical methods, injury-to-surgery interval, preoperative traction, weight-bearing time, and implant removal. All patients were followed for a mean of 52 months (range, 6-90 months). The incidence of femoral head necrosis was 14.4% (21/146). Garden classification (P=.012), reduction quality (P=.008), implant removal (P=.020), and preoperative traction (P=.003) were significantly associated with femoral head necrosis. Patient age (P=.990), sex (P=.287), injury-to-surgery interval (P=.360), weight-bearing time (P=.868), and surgical methods (P=.987) were not significantly associated with femoral head necrosis. In multivariate logistic regression analysis, implant removal was not a significant risk factor for femoral head necrosis development (P=.498). Garden classification, reduction quality, and preoperative traction had a significant effect on femoral head necrosis development.
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17
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Pauyo T, Drager J, Albers A, Harvey EJ. Management of femoral neck fractures in the young patient: A critical analysis review. World J Orthop 2014; 5:204-217. [PMID: 25035822 PMCID: PMC4095012 DOI: 10.5312/wjo.v5.i3.204] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Revised: 04/17/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Femoral neck fractures account for nearly half of all hip fractures with the vast majority occurring in elderly patients after simple falls. Currently there may be sufficient evidence to support the routine use of hip replacement surgery for low demand elderly patients in all but non-displaced and valgus impacted femoral neck fractures. However, for the physiologically young patients, preservation of the natural hip anatomy and mechanics is a priority in management because of their high functional demands. The biomechanical challenges of femoral neck fixation and the vulnerability of the femoral head blood supply lead to a high incidence of non-union and osteonecrosis of the femoral head after internal fixation of displaced femoral neck fractures. Anatomic reduction and stable internal fixation are essentials in achieving the goals of treatment in this young patient population. Furthermore, other management variables such as surgical timing, the role of capsulotomy and the choice of implant for fixation remain controversial. This review will focus both on the demographics and injury profile of young patients with femoral neck fractures and the current evidence behind the surgical management of these injuries as well as their major secondary complications.
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18
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Kumar MN, Belehalli P, Ramachandra P. PET/CT study of temporal variations in blood flow to the femoral head following low-energy fracture of the femoral neck. Orthopedics 2014; 37:e563-70. [PMID: 24972438 DOI: 10.3928/01477447-20140528-57] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2013] [Accepted: 11/25/2013] [Indexed: 02/03/2023]
Abstract
Earlier studies on femoral neck fractures have assessed the blood flow in either the pre- or postoperative period and information is lacking regarding changes in vascular flow to the femoral head after injury. Sixty-two adults with low-energy intracapsular femoral neck fractures were studied prospectively. Mean patient age was 57.2 years (range, 45-82 years). All patients underwent positron emission tomography/computed tomography (PET/CT) prior to surgical intervention and 6 weeks after internal fixation. Internal fixation was done using cannulated cancellous titanium screws and serial follow-up radiographs were obtained (at monthly intervals for the first 3 months followed by 3 monthly intervals between radiographs up to 2 years). On the preoperative PET/CT, 13 patients showed intact vascularity, 31 showed total loss of vascularity, and 18 showed partial loss of vascularity of the femoral head. The 6-week postoperative PET/CT scan showed recovery of blood supply in 23 of the 31 patients with total loss of vascularity and 15 of the 18 patients with partial loss of vascularity of the femoral head. Eleven of 62 patients had total or partial avascularity at the 6-week postoperative PET/CT scan and all 11 patients showed evidence of avascular necrosis on plain radiographs at the end of 2 years. The association between the vascular status of the femoral head at 6 weeks and avascular necrosis at the end of 2 years was statistically significant (P<.001). This study shows that the femoral head undergoes temporal variations in blood flow following femoral neck fracture. Decreased or absent vascularity is seen in approximately 75% of the fractures and 80% of the femoral heads with initial vascular compromise seem to regain blood flow within 6 weeks. Thus, prognostication about vascularity based on single-point preoperative imaging is difficult. The 6-week postoperative PET/CT scan seems to be reliable in predicting the future status of the femoral head. However, decision making regarding hemiarthroplasty or internal fixation at the time of injury may have to depend on factors other than the preoperative vascular status of the femoral head.
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19
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Tumor necrosis factor stimulates osteoclastogenesis from human bone marrow cells under hypoxic conditions. Exp Cell Res 2014; 321:167-77. [DOI: 10.1016/j.yexcr.2013.11.020] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2013] [Revised: 11/06/2013] [Accepted: 11/27/2013] [Indexed: 02/07/2023]
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20
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Sarkar S, Germeraad WTV, Rouschop KMA, Steeghs EMP, van Gelder M, Bos GMJ, Wieten L. Hypoxia induced impairment of NK cell cytotoxicity against multiple myeloma can be overcome by IL-2 activation of the NK cells. PLoS One 2013; 8:e64835. [PMID: 23724099 PMCID: PMC3665801 DOI: 10.1371/journal.pone.0064835] [Citation(s) in RCA: 128] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2012] [Accepted: 04/19/2013] [Indexed: 12/15/2022] Open
Abstract
Background Multiple Myeloma (MM) is an incurable plasma cell malignancy residing within the bone marrow (BM). We aim to develop allogeneic Natural Killer (NK) cell immunotherapy for MM. As the BM contains hypoxic regions and the tumor environment can be immunosuppressive, we hypothesized that hypoxia inhibits NK cell anti-MM responses. Methods NK cells were isolated from healthy donors by negative selection and NK cell function and phenotype were examined at oxygen levels representative of hypoxic BM using flowcytometry. Additionally, NK cells were activated with IL-2 to enhance NK cell cytotoxicity under hypoxia. Results Hypoxia reduced NK cell killing of MM cell lines in an oxygen dependent manner. Under hypoxia, NK cells maintained their ability to degranulate in response to target cells, though, the percentage of degranulating NK cells was slightly reduced. Adaptation of NK- or MM cells to hypoxia was not required, hence, the oxygen level during the killing process was critical. Hypoxia did not alter surface expression of NK cell ligands (HLA-ABC, -E, MICA/B and ULBP1-2) and receptors (KIR, NKG2A/C, DNAM-1, NCRs and 2B4). It did, however, decrease expression of the activating NKG2D receptor and of intracellular perforin and granzyme B. Pre-activation of NK cells by IL-2 abrogated the detrimental effects of hypoxia and increased NKG2D expression. This emphasized that activated NK cells can mediate anti-MM effects, even under hypoxic conditions. Conclusions Hypoxia abolishes the killing potential of NK cells against multiple myeloma, which can be restored by IL-2 activation. Our study shows that for the design of NK cell-based immunotherapy it is necessary to study biological interactions between NK- and tumor cells also under hypoxic conditions.
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Affiliation(s)
- Subhashis Sarkar
- Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Wilfred T. V. Germeraad
- Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Kasper M. A. Rouschop
- Department of Radiation Oncology (Maastro Lab), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Elisabeth M. P. Steeghs
- Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Michel van Gelder
- Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Gerard M. J. Bos
- Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Lotte Wieten
- Department of Transplantation Immunology, Maastricht University Medical Center+, Maastricht, The Netherlands
- * E-mail:
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Gao YS, Guo SC, Ding H, Zhang CQ. Caspase-3 may be employed as an early predictor for fracture‑induced osteonecrosis of the femoral head in a canine model. Mol Med Rep 2012; 6:611-4. [PMID: 22735815 DOI: 10.3892/mmr.2012.958] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2012] [Accepted: 06/15/2012] [Indexed: 11/06/2022] Open
Abstract
The aim of the current study was to investigate the local expression of caspase-3 following femoral neck fractures in a canine model and to investigate its effect on the occurrence of fracture-induced osteonecrosis of the femoral head (ONFH). Eight dogs had surgically-induced femoral neck fractures on the left side which remained untreated. Radiological and histological examinations were employed to detect morphological changes of the femoral head. Immunohistochemical staining of caspase-3 was used to evaluate cell apoptosis, which may play an important role in ONFH. The results were compared to the normal side for statistical analysis. As a result, all eight dogs had ONFH, with non-union in five and malunion in three on radiological examination. Histologically, the untreated femoral heads developed osteonecrosis with an accumulation of bone marrow cell debris, empty lacunae and/or ghost nuclei in the lacunae, and an increase in the number of fat cells. Immunohistochemical staining of caspase-3 indicated that it was upregulated in fracture-induced ONFH two weeks postoperatively, which showed a statistical difference when compared to the normal side. In conclusion, the local expression of caspase-3 was upregulated in fracture-induced ONFH, suggesting that cell apoptosis is crucial in traumatic ONFH. Caspase-3 may therefore be employed as an effective and early predictor for fracture-induced ONFH.
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Affiliation(s)
- You-Shui Gao
- Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, PR China
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22
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Abstract
OBJECTIVES The aim of our study was to develop a minimally invasive endoscopic procedure (osteoscopy), which is capable of visualizing blood supply and quantitatively assessing circulation to the femoral head at the time of definitive surgery. METHODS The new diagnostic technique was developed in animal experiments (four piglets) and was subsequently tested in nine consecutive patients requiring surgery for a femoral neck fracture. The direct visualization of the femoral head circulation was performed in the mortise prepared for the implant. The osteoscope optic fiber was placed at the orifice of the cavity created by the custom-made drill bit. The "mortise-sleeve-optic" system was connected to a manometer and a saline reservoir. The bleeding from the wall of bony cavity was observed, meanwhile the inner pressure of the "mortise-sleeve-optic" system was changed gradually. The pressure measurement at the first appearance of bleeding and the intraosseal pressure was recorded. RESULTS The animal investigations demonstrated that the osteoscopy readily distinguished among diffuse bleeding, pulsatile bleeding, and the absence of bleeding in the femoral head. The human experiments proved that a different quality of the femoral head circulation can be observed during osteoscopy. CONCLUSIONS Preliminary findings indicate that clinical osteoscopy may be a useful tool in the assessment of blood circulation to the femoral head.
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23
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Sebestyén A, Boncz I, Tóth F. Intra-operative femoral head vascularity assessment: An innovative and simple technique (Letter 2). Indian J Orthop 2012; 46:114-5. [PMID: 22345821 PMCID: PMC3270598 DOI: 10.4103/0019-5413.91649] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Andor Sebestyén
- National Health Insurance Fund, South-Transdanubian Regional Office, Pécs, Hungary,Address for correspondence: Dr. Andor Sebestyén, National Health Insurance Fund South-Transdanubian Regional Office, Pécs, Hungary, Pécs H 7623, Nagy Lajos király ut 3, Hungary. E-mail:
| | - Imre Boncz
- Institute for Health Insurance, University of Pécs, Pécs, Hungary
| | - Ferenc Tóth
- CARE UK Ltd, NHS Barlborough Treatment Centre, UK
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24
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Zhao Y, Chen G, Zhang W, Xu N, Zhu JY, Jia J, Sun ZJ, Wang YN, Zhao YF. Autophagy regulates hypoxia-induced osteoclastogenesis through the HIF-1α/BNIP3 signaling pathway. J Cell Physiol 2011; 227:639-48. [DOI: 10.1002/jcp.22768] [Citation(s) in RCA: 111] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Martin SK, Diamond P, Gronthos S, Peet DJ, Zannettino ACW. The emerging role of hypoxia, HIF-1 and HIF-2 in multiple myeloma. Leukemia 2011; 25:1533-42. [PMID: 21637285 DOI: 10.1038/leu.2011.122] [Citation(s) in RCA: 93] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hypoxia is an imbalance between oxygen supply and demand, which deprives cells or tissues of sufficient oxygen. It is well-established that hypoxia triggers adaptive responses, which contribute to short- and long-term pathologies such as inflammation, cardiovascular disease and cancer. Induced by both microenvironmental hypoxia and genetic mutations, the elevated expression of the hypoxia-inducible transcription factor-1 (HIF-1) and HIF-2 is a key feature of many human cancers and has been shown to promote cellular processes, which facilitate tumor progression. In this review, we discuss the emerging role of hypoxia and the HIFs in the pathogenesis of multiple myeloma (MM), an incurable hematological malignancy of BM PCs, which reside within the hypoxic BM microenvironment. The need for current and future therapeutic interventions to target HIF-1 and HIF-2 in myeloma will also be discussed.
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Affiliation(s)
- S K Martin
- Division of Haematology, Centre for Cancer Biology, SA Pathology, CSCR, University of Adelaide, Adelaide, South Australia
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26
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Ehlinger M, Moser T, Adam P, Bierry G, Gangi A, de Mathelin M, Bonnomet F. Early prediction of femoral head avascular necrosis following neck fracture. Orthop Traumatol Surg Res 2011; 97:79-88. [PMID: 21087905 DOI: 10.1016/j.otsr.2010.06.014] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2010] [Revised: 05/28/2010] [Accepted: 06/21/2010] [Indexed: 02/02/2023]
Abstract
Femoral neck fracture puts at risk functional prognosis in young patients and can be life-threatening in the elderly. The present study reviews methods of femoral head vascularity assessment following neck fracture, to address the following issues: what is the risk of osteonecrosis? And what, in the light of this risk, is the best-adapted treatment to avoid iterative surgery? Femoral head vascularity depends on retinacular vessels and especially the lateral epiphyseal artery, which contributes from 70 to 80% of the femoral head vascular supply. Fracture causes vascular lesions, which are in turn the prime cause of necrosis. Other factors combine with this: hematoma tamponade effect, reduced joint space and increased pressure due to lower extremity positioning in extension/internal rotation/abduction during surgery. Head deformity is not due to direct cell death but to the repair process originating from the surrounding living bone. In post-traumatic necrosis, proliferation rapidly invades the head, with significant osteogenesis. Pathologic fractures occur at the boundary between the new and dead bone. Many techniques have been reported to help assess residual hemodynamics and risk of necrosis. Some are invasive: superselective angiography, intra-osseous oxygen pressure measurement, or Doppler-laser hemodynamic measurement; others involve imaging: scintigraphy, conventionnal or dynamic MRI. The future seems to lie with dynamic MRI, which allows a new classification of femoral neck fractures, based on a non-invasive assessment of femoral head vascularity.
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Affiliation(s)
- M Ehlinger
- Orthopedic Surgery and Traumatology Department, Hautepierre Hospital, Strasbourg University Hospitals, 1, avenue Molière, 67098 Strasbourg cedex, France.
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Knowles HJ, Athanasou NA. Acute hypoxia and osteoclast activity: a balance between enhanced resorption and increased apoptosis. J Pathol 2009; 218:256-64. [PMID: 19291710 DOI: 10.1002/path.2534] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Osteoclasts are the primary mediators of pathological bone resorption in many conditions in which micro-environmental hypoxia is associated with disease progression. However, effects of hypoxia on human osteoclast activity have not been reported. Mature human osteoclasts were differentiated from peripheral blood or obtained from giant cell tumour of bone. Osteoclasts were exposed to a constant hypoxic environment and then assessed for parameters including resorption (toluidine blue staining of dentine slices), membrane integrity (trypan blue exclusion), apoptosis (TUNEL, DAPI), and osteolysis-associated enzyme activity (TRAP, cathepsin K). 24 h exposure to 2% O(2) produced a 2.5-fold increase in resorption associated with increased TRAP and cathepsin K enzyme activity. Hypoxia-Inducible Factor-1alpha (HIF-1alpha) siRNA completely ablated the hypoxic increase in osteoclast resorption. 24 h at 2% O(2) also increased the number of osteoclasts with compromised membrane integrity from 6% to 21%, with no change in the total osteoclast number or the proportion of late-stage apoptotic cells. Transient reoxygenation returned the percentage of trypan blue-positive cells to normoxic levels, suggesting that osteoclasts can recover from the early stages of cell death. Repeated over an extended period, hypoxia/reoxygenation enhanced osteoclast differentiation at this pO(2). These data suggest that in diseased bone, where the pO(2) may fall to <or=2% O(2), a delicate balance between hypoxia-induced osteoclast activation and hypoxia-induced osteoclast apoptosis mediates pathological bone resorption.
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Affiliation(s)
- Helen J Knowles
- Botnar Research Centre, University of Oxford, Nuffield Orthopaedic Centre, Oxford, UK.
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Finch ME, McGrory BJ. Osteonecrosis of the femoral head after subtrochanteric fracture: a case report. CURRENT ORTHOPAEDIC PRACTICE 2009. [DOI: 10.1097/bco.0b013e3181944d99] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Rubin LE, Galante NJ, Smith BG, DeLuca PA. Direct intraosseous pressure monitoring of the femoral head during surgery for slipped capital femoral epiphysis. Orthopedics 2008; 31:663-6. [PMID: 18705558 DOI: 10.3928/01477447-20110505-11] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Preventing avascular necrosis following surgical management of pediatric slipped capital femoral epiphysis is a critical goal. The direct intraosseous pressure monitor is a readily available and affordable technique that can easily be used by surgeons around the world.
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Affiliation(s)
- Lee E Rubin
- Department of Orthopaedics and Rehabilitation, Yale-New Haven Hospital, New Haven, Connecticut 06520, USA
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