|
1
|
Glueck CJ. Thrombophilia, hypofibrinolysis and osteonecrosis. ORTHOPADIE (HEIDELBERG, GERMANY) 2025; 54:376-385. [PMID: 39969562 DOI: 10.1007/s00132-024-04606-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/16/2024] [Indexed: 02/20/2025]
Abstract
Anticoagulation in most patients with familial thrombophilia-hypofibrinolysis and primary osteonecrosis (ON) before hip or knee collapse relieves pain, prevents joint collapse and usually averts the need for joint replacement but is not successful in secondary ON or if started after joint collapse. Anticoagulation in Perthes disease and in ON acutely appearing in post-COVID patients, particularly when factor V Leiden is present, may be valuable as an approach to prevent the otherwise high likelihood of subsequent joint failure. Anticoagulation in primary ON with concurrent thrombophilia-hypofibrinolysis should be considered within the treatment spectrum of ON.
Collapse
Affiliation(s)
- Charles J Glueck
- Cholesterol, Metabolism, and Thrombosis Research Center, Middleton Ave, 3906, Cincinnati, OH, USA.
| |
Collapse
|
|
2
|
Lou Y, Wu J, Zhong Y, Tong P, Du W. Etiology, pathology, and treatment of osteonecrosis of the femoral head in adolescents: A comprehensive review. Medicine (Baltimore) 2024; 103:e39102. [PMID: 39058826 PMCID: PMC11272257 DOI: 10.1097/md.0000000000039102] [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: 02/09/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Femoral head necrosis is a common refractory disease in orthopedics, and shows a trend of getting younger. The occurrence of femoral head necrosis in adolescents is related to the use of glucocorticoids, autoimmune diseases, trauma, and other factors. Because adolescent patients are in the period of physical development, high activity requirements, and have fertility needs in the future, treatment is relatively difficult. Early artificial joint replacement may have problems such as wear and loosening, so total hip replacement is not the preferred treatment for adolescent patients with femoral head necrosis. This article will elaborate the research progress of femoral head necrosis in adolescents from 3 aspects, and summarize the benefits and side effects of core decompression combined with autologous stem cell transplantation in the treatment of early femoral head necrosis, so as to provide clinical ideas for the treatment of femoral head necrosis in adolescents.
Collapse
Affiliation(s)
- Yuhan Lou
- Jinhua Hospital of Traditional Chinese Medicine, Jinhua, China
| | - Jiawen Wu
- Jinhua Hospital of Traditional Chinese Medicine, Jinhua, China
| | - Ying Zhong
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Peijian Tong
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Wenxi Du
- The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| |
Collapse
|
|
3
|
Ko YS, Ha JH, Park JW, Lee YK, Kim TY, Koo KH. Updating Osteonecrosis of the Femoral Head. Hip Pelvis 2023; 35:147-156. [PMID: 37727298 PMCID: PMC10505838 DOI: 10.5371/hp.2023.35.3.147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Revised: 06/16/2023] [Accepted: 06/16/2023] [Indexed: 09/21/2023] Open
Abstract
Osteonecrosis of the femoral head (ONFH), a condition characterized by the presence of a necrotic bone lesion in the femoral head, is caused by a disruption in the blood supply. Its occurrence is more common in young and middle-aged adults and it is the main reason for performance of total hip arthroplasty in this age group. Its incidence is increasing along with increased use of glucocorticoids for management of adjuvant therapy for treatment of leukemia as well as organ transplantation and other myelogenous diseases. Current information on etiology and pathogenesis, as well as natural history, stage system, and treatments is provided in this review. A description of the Association Research Circulation Osseous (ARCO) criteria for classification of glucocorticoids- and alcohol-associated ONFH, 2019 ARCO staging system, and 2021 ARCO classification using computed tomography for the early stages of ONFH is also provided.
Collapse
Affiliation(s)
- Young-Seung Ko
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Joo Hyung Ha
- Department of Orthopaedic Surgery, Gumdan Top General Hospital, Incheon, Korea
| | - Jung-Wee Park
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young-Kyun Lee
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Tae-Young Kim
- Department of Orthopaedic Surgery, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Kyung-Hoi Koo
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seongnam, Korea
- Kay Joint Center at Cheil Orthopaedic Hospital, Seoul, Korea
| |
Collapse
|
|
4
|
Woerner M, Voelkl K, Bliemel C, Ferner F, Weber M, Renkawitz T, Grifka J, Craiovan B. Comparison of two joint-preserving treatments for osteonecrosis of the femoral head: core decompression and core decompression with additional cancellous bone grafting. J Int Med Res 2023; 51:3000605231190453. [PMID: 37585739 PMCID: PMC10416661 DOI: 10.1177/03000605231190453] [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: 10/28/2022] [Accepted: 07/11/2023] [Indexed: 08/18/2023] Open
Abstract
OBJECTIVE Femoral head necrosis (FHN) affects mostly young and active people. The most common operative therapy is core decompression (CD) with optional cancellous bone grafting (CBG). Because little information is available on the long-term results of these procedures, we investigated the effectiveness of CD and CD + CBG in patients with ARCO stage II FHN in terms of postoperative pain, range of motion, patient-reported outcome measures (Harris Hip Score, Hip Disability and Osteoarthritis Outcome Score, EuroQol 5D, and Short Form 36 Questionnaire), and disease progression. METHODS We retrospectively compared 11 patients treated with CD alone 48.0 months (range, 26.3-68.5 months) postoperatively versus 11 patients treated with CD + CBG 69.2 months (range, 38.0-92.9 months) postoperatively. All patients were assessed according to a routine clinical protocol involving a clinical examination, questionnaires, and radiological imaging (X-ray and magnetic resonance imaging). RESULTS The clinical and radiological results showed no significant differences between the two groups. Both interventions demonstrated equal results according to clinical scores. CONCLUSIONS Our data may encourage application of the less invasive technique of CD alone without CBG, which is more surgically demanding. Further prospective studies with longer follow-up are necessary to clarify the risk factors for therapy failure.
Collapse
Affiliation(s)
- Michael Woerner
- Klinikum Bamberg, Klinik für Orthopädie und Unfallchirurgie, Buger Strasse 80, Bamberg
- Universitätsklinikum Regensburg Klinik für Orthopädie, Kaiser-Karl V-Allee 3, Bad Abbach
- Universitätsklinikum Regensburg, Klinik für Orthopädie, Kaiser-Karl V-Allee 3, Bad Abbach
| | - Korbinian Voelkl
- Universitätsklinikum Regensburg Klinik für Orthopädie, Kaiser-Karl V-Allee 3, Bad Abbach
| | - Christopher Bliemel
- Universitätsklinikum Marburg, Klinik für Orthopädie und Unfallchirurgie, Baldingertrasse, Marburg
| | - Felix Ferner
- Klinikum Lichtenfels, Klinik für Orthopädie und Unfallchirurgie, Professor-Arneth-Straße 2b, Lichtenfels
| | - Markus Weber
- Universitätsklinikum Regensburg, Franz-Josef-Strauß-Allee 11, Regensburg
| | - Tobias Renkawitz
- Universitätsklinikum Heidelberg, Klinik für Orthopädie, Schlierbacher Landstraße 200a, Heidelberg
| | - Joachim Grifka
- Universitätsklinikum Regensburg Klinik für Orthopädie, Kaiser-Karl V-Allee 3, Bad Abbach
| | - Benjamin Craiovan
- Universitätsklinikum Regensburg Klinik für Orthopädie, Kaiser-Karl V-Allee 3, Bad Abbach
- Universitätsklinikum Marburg, Klinik für Orthopädie und Unfallchirurgie, Baldingertrasse, Marburg
- Universitätsklinikum Regensburg, Klinik für Orthopädie, Kaiser-Karl V-Allee 3, Bad Abbach
| |
Collapse
|
|
5
|
Avascular necrosis of the femoral head: three-dimensional measurement of drilling precision reveals high accuracy and no difference between fluoroscopically controlled core decompression and cancellous bone grafting. Arch Orthop Trauma Surg 2023:10.1007/s00402-022-04753-2. [PMID: 36656351 DOI: 10.1007/s00402-022-04753-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Accepted: 12/28/2022] [Indexed: 01/20/2023]
Abstract
INTRODUCTION Avascular osteonecrosis of the femoral head (AVN) is a widespread disease affecting mostly young and active people, often exacerbating in progressive stages, ending in joint replacement. The most common joint preserving operative therapy for early stages is core decompression (CD), optional with cancellous bone grafting (CBG). For success it is vital that the necrotic area is hit and the sclerotic rim is broken by drilling into the defect zone to relieve intraosseous pressure. The aim of this study was to investigate if both techniques are precise enough to hit the center of the necrosis and if there is a difference in precision between drilling with small pins (CD) and the trephine (CBG). PATIENTS AND METHODS 10 patients underwent CD, 12 patients CBG with conventional C-arm imaging. Postoperatively 3D MRI reconstructions of the necrotic area and the drilling channels were compared. The deviation of the drilling channel from the center of the necrotic area was measured. PROMs (HHS, HOOS, EQ-5D, SF-36) were evaluated to compare the clinical success of these procedures. RESULTS Neither with CD nor with CBG the defect zone was missed. The drilling precision of both procedures did not differ significantly: distance to center 3.58 mm for CD (range 0.0-14.06, SD 4.2) versus 3.91 mm for CBG (range 0.0-15.27, SD 4.7). PROMs showed no significant difference. CONCLUSION Concerning the most important difference between the two procedures-the surgical higher demanding technique of CBG-we suggest applying the less invasive technique of CD alone.
Collapse
|
|
6
|
Teimouri M, Motififard M, Hatami S. Etiology of Femoral Head Avascular Necrosis in Patients: A Cross-Sectional Study. Adv Biomed Res 2022; 11:115. [PMID: 36798919 PMCID: PMC9926026 DOI: 10.4103/abr.abr_235_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 11/20/2021] [Accepted: 11/23/2021] [Indexed: 12/28/2022] Open
Abstract
Background Avascular necrosis (AVN), known as osteonecrosis, aseptic necrosis, or ischemic bone necrosis, results in the destruction of bone cells. In the present study, we aimed to report the most common causes of AVN in in patients referred to Isfahan educational and medical centers. Materials and Methods This study is a cross-sectional study that was performed on all patients with AVN in medical educational centers in Isfahan during 2019 and 2020. We included all patients diagnosed with AVN. Patients' information including age, sex, cause of femoral head necrosis, medical history, and drug usage were collected. Finally, reliable data from 99 patients were recorded. Results We collected data of 99 patients in this study. The most prevalent cause of ANV was corticosteroids use (32.3%), and it was more prevalent among women (51.4%); the second prevalent cause of AVN in our study sample was trauma (28.28%), and it was more prevalent among men (32.8%). Conclusion The most common cause of AVN was corticosteroids, which was consistent with previous studies. Other main causes of AVN were traumatic or idiopathic issues.
Collapse
Affiliation(s)
- Mehdi Teimouri
- Department of Orthopedic Surgery, School of Medicine, Kashani University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehdi Motififard
- Department of Orthopedic Surgery, School of Medicine, Kashani University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Saeed Hatami
- Department of Orthopedic Surgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran,Address for correspondence: Dr. Saeed Hatami, Department of Orthopedic Surgery School of Medicine, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran. E-mail:
| |
Collapse
|
|
7
|
Association of Nitric Oxide Synthase Polymorphism and Coagulopathy in Patients with Osteonecrosis of the Femoral Head. J Clin Med 2022; 11:jcm11174963. [PMID: 36078892 PMCID: PMC9457043 DOI: 10.3390/jcm11174963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/17/2022] [Accepted: 08/20/2022] [Indexed: 11/19/2022] Open
Abstract
Genetic polymorphism of nitric oxide synthase (NOS) can cause reduction of nitric oxide (NO) levels and may be associated with osteonecrosis of the femoral head (ONFH). However, the association of coagulopathy and NOS polymorphism in ONFH patients has not been confirmed. Between November 2005 and October 2013, 155 patients with ONFH were recruited in the study of serum coagulation profiles and NOS polymorphism. Another 43 patients who had dysplasia, osteoarthritis, or trauma of hip joints were included as controls. PCR genotyping for the analysis of NOS 27-bp polymorphism in intron 4 was performed. The analysis of coagulation profiles included fibrinogen, fibrinogen degradation product (FDP), protein S, protein C, and anti-thrombin III. The results showed that 27-bp repeat polymorphism was significantly associated with ONFH (OR 4.32). ONFH patients had significantly higher fibrinogen, FDP, protein S, and anti-thrombin III levels than that of the controls. The incidence of coagulopathy was significantly higher in ONFH patients (73.2%), and the odds ratio increased from 2.38 to 7.33 when they had 27-bp repeat polymorphism. Patients with hyperfibrinogenemia, elevated FDP levels, and with the risk factor of alcohol or steroid use had significantly higher risks of bilateral hip involvement. This study demonstrated the presence of NOS polymorphism, and a resultant reduction in NO production was associated with coagulopathy, which in turn might contribute to higher risks of bilateral ONFH. Our data suggests that checking NOS polymorphism and coagulopathy may provide a new avenue in managing ONFH.
Collapse
|
|
8
|
Lin RLC, Sung PH, Wu CT, Tu YK, Lu YD, Yip HK, Lee MS. Decreased Ankyrin Expression Is Associated with Repressed eNOS Signaling, Cell Proliferation, and Osteogenic Differentiation in Osteonecrosis of the Femoral Head. J Bone Joint Surg Am 2022; 104:2-12. [PMID: 35389901 DOI: 10.2106/jbjs.20.00465] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND Reduced nitric oxide synthase (NOS) activity and decreased reparative potentials in stem cells may be involved in the pathogenesis of osteonecrosis of the femoral head (ONFH), but the underlying mechanism is not clear. Ankyrin, a cytoskeletal protein, can promote NOS expression and many cellular functions when it interacts with the CD44 receptors on the stem cells. This study investigated whether ankyrin is involved in the pathogenesis of ONFH. MATERIALS AND METHODS Bone marrow stem cells (BMSCs) from ONFH patients were compared with cells from patients with proximal femoral fracture and BMSC cell lines (PT-2501, Lonza, NC, USA). Differences in the expression levels and downstream signal pathway of ankyrin-Akt-eNOS in BMSCs were studied between ONFH and control. The involvement of ankyrin in the signal cascade, cell proliferation, and differentiation were further investigated by silencing ankyrin using small interfering (si)RNA. RESULTS We found the basal mRNA levels of ankyrin and CD44 in BMSCs from the ONFH group were significantly lower as compared with those from the control group. The signal transduction of CD44-ankyrin-Akt-eNOS was significantly repressed in the ONFH group as compared with the control group after hyaluronic acid treatment. Knockdown of ankyrin by siRNA could attenuate the eNOS signaling as well as the BMSCs proliferation and osteogenic differentiation. The proliferation ability and osteogenic differentiation potential of the BMSCs from the ONFH group were significantly reduced as compared with the control group, but they can be enhanced to the baseline levels of the control group by hyaluronic acid treatment. CONCLUSION The aberrant eNOS signaling, reduced cell proliferation, and osteogenic differentiation potential in BMSCs from ONFH patients are associated with the decreased ankyrin expression. CLINICAL RELEVANCE Altered signal transduction, proliferation, and osteogenic differentiation ability in BMSCs may be involved in the pathogenesis of ONFH. These need further studies especially in BMSC-based cell therapy.
Collapse
Affiliation(s)
- Rio L C Lin
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Pei-Hsun Sung
- Department of Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Chen-Ta Wu
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Yuan-Kun Tu
- Department of Orthopedic Surgery, EDa Hospital, Kaohsiung, Taiwan
| | - Yu-Der Lu
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Hon-Kan Yip
- Department of Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| | - Mel S Lee
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Taiwan
| |
Collapse
|
|
9
|
Hines JT, Jo WL, Cui Q, Mont MA, Koo KH, Cheng EY, Goodman SB, Ha YC, Hernigou P, Jones LC, Kim SY, Sakai T, Sugano N, Yamamoto T, Lee MS, Zhao D, Drescher W, Kim TY, Lee YK, Yoon BH, Baek SH, Ando W, Kim HS, Park JW. Osteonecrosis of the Femoral Head: an Updated Review of ARCO on Pathogenesis, Staging and Treatment. J Korean Med Sci 2021; 36:e177. [PMID: 34155839 PMCID: PMC8216992 DOI: 10.3346/jkms.2021.36.e177] [Citation(s) in RCA: 101] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 05/25/2021] [Indexed: 11/22/2022] Open
Abstract
Non-traumatic osteonecrosis of the femoral head (ONFH) usually affects adults younger than 50 years and frequently leads to femoral head collapse and subsequent arthritis of the hip. It is becoming more prevalent along with increasing use of corticosteroids for the adjuvant therapy of leukemia and other myelogenous diseases as well as management of organ transplantation. This review updated knowledge on the pathogenesis, classification criteria, staging system, and treatment of ONFH.
Collapse
Affiliation(s)
- Jeremy T Hines
- Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Woo Lam Jo
- Department of Orthopaedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Quanjun Cui
- Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Michael A Mont
- Department of Orthopaedic Surgery, Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Kyung Hoi Koo
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
| | - Edward Y Cheng
- Department of Orthopaedic Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Stuart B Goodman
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, CA, USA
| | - Yong Chan Ha
- Department of Orthopaedic Surgery, Chung-Ang University College of Medicine, Seoul, Korea
| | | | - Lynne C Jones
- Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Shin Yoon Kim
- Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Takashi Sakai
- Department of Orthopedic Surgery, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan
| | - Nobuhiko Sugano
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Takuaki Yamamoto
- Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Mel S Lee
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Dewei Zhao
- Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Wolf Drescher
- Department of Orthopedic Surgery, RWTH University Hospital, Aachen, Germany
| | - Tae Young Kim
- Department of Orthopaedic Surgery, Konkuk University College of Medicine, Seoul, Korea
| | - Young Kyun Lee
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Byung Ho Yoon
- Department of Orthopaedic Surgery, Ewha Womans University College of Medicine, Seoul, Korea
| | - Seung Hoon Baek
- Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu, Korea
| | - Wataru Ando
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hong Seok Kim
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jung Wee Park
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| |
Collapse
|
|
10
|
Quaranta M, Miranda L, Oliva F, Aletto C, Maffulli N. Osteotomies for avascular necrosis of the femoral head. Br Med Bull 2021; 137:98-111. [PMID: 33454780 DOI: 10.1093/bmb/ldaa044] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 11/27/2020] [Accepted: 11/27/2020] [Indexed: 11/14/2022]
Abstract
BACKGROUND In osteonecrosis of the femoral head (ONFH), blood supply is insufficient for the metabolic requirements of the bone. The initial management is conservative, and, in case of failure, surgery is indicated. Osteotomies aim to change the spatial position of the necrotic portion of the femoral head. This systematic review evaluates the effectiveness and safety of osteotomies for ONFH. SOURCE OF DATA The systematic review, organized, conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, was performed on PubMed and Google Scholar. We analysed outcomes in term of Harris Hip Score, leg shortening, secondary collapse and blood loss. We also verified the percentage of patients who required total hip replacement (THR) after osteotomy for ONFH. AREAS OF AGREEMENT A total of 16 articles were selected, including 775 patients and 852 osteotomies [curved varus osteotomy in 369 (43.3%) patients; transtrochanteric rotational osteotomy in 435 (51.05%) patients; half wedge osteotomy in 48 (5.6%) patients]. There was an overall THR conversion rate of 31.5% (268 hips on 852 osteotomies). AREAS OF CONTROVERSY There were no prospective randomized trials, and the outcome measures employed were often heterogeneous. GROWING POINTS Approximately one-third of the osteotomies performed in cases of ONFH are converted to THR over a period of ~7 years. In older patients, primary THR should be considered, especially as the conversion to THR after osteotomy is technically demanding. AREAS TIMELY FOR DEVELOPING RESEARCH Randomized clinical studies should be conducted in order to define the parameters of the patient that can direct towards the most suitable osteotomic technique.
Collapse
Affiliation(s)
- Marco Quaranta
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, 84084 Baronissi, Italy.,Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, 84131 Salerno, Italy
| | - Luca Miranda
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, 84084 Baronissi, Italy.,Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, 84131 Salerno, Italy
| | - Francesco Oliva
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, 84084 Baronissi, Italy.,Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, 84131 Salerno, Italy
| | - Cristian Aletto
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, 84084 Baronissi, Italy.,Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, 84131 Salerno, Italy
| | - Nicola Maffulli
- Department of Musculoskeletal Disorders, Faculty of Medicine and Surgery, University of Salerno, 84084 Baronissi, Italy.,Clinica Ortopedica, Ospedale San Giovanni di Dio e Ruggi D'Aragona, 84131 Salerno, Italy.,Queen Mary University of London, Barts and the London School of Medicine and Dentistry, Centre for Sports and Exercise Medicine, Mile End Hospital, 275 Bancroft Road, London E1 4DG UK.,Faculty of Medicine, School of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Thornburrow Drive, Hartshill, Stoke-on-Trent ST4 7QB, UK
| |
Collapse
|
|
11
|
Cui Q, Jo WL, Koo KH, Cheng EY, Drescher W, Goodman SB, Ha YC, Hernigou P, Jones LC, Kim SY, Lee KS, Lee MS, Lee YJ, Mont MA, Sugano N, Taliaferro J, Yamamoto T, Zhao D. ARCO Consensus on the Pathogenesis of Non-traumatic Osteonecrosis of the Femoral Head. J Korean Med Sci 2021; 36:e65. [PMID: 33724736 PMCID: PMC7961868 DOI: 10.3346/jkms.2021.36.e65] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 01/08/2021] [Indexed: 02/04/2023] Open
Abstract
Osteonecrosis of the femoral head (ONFH) is a devastating disease frequently leading to femoral head collapse and hip arthritis. Specifically, non-traumatic ONFH primarily affects young and middle-aged adults. Although compromised local circulation of the femoral head seems to be pathognomonic for the disease, the pathogenesis is perplexing and continues to be an area of scrutiny and research. Comprehension of the pathogenesis is of crucial importance for developing and guiding treatments for the disease. Therefore, we provide an up-to-date consensus on the pathogenesis of non-traumatic ONFH.
Collapse
Affiliation(s)
- Quanjun Cui
- Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Woo Lam Jo
- Department of Orthopaedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
| | - Kyung Hoi Koo
- Department of Orthopaedic Surgery, Seoul National University Bundang Hospital and Medical College of Seoul National University, Seongnam, Korea
| | - Edward Y Cheng
- Department of Orthopaedic Surgery, University of Minnesota Medical School, Minneapolis, MN, USA
| | - Wolf Drescher
- Department of orthopedic surgery, RWTH University Hospital, Aachen, Germany
| | - Stuart B Goodman
- Department of Orthopaedic Surgery, Stanford University School of Medicine, Redwood City, CA, USA
| | - Yong Chan Ha
- Department of Orthopaedic Surgery, Chung-Ang University College of Medicine, Seoul, Korea
| | | | - Lynne C Jones
- Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Shin Yoon Kim
- Department of Orthopedic Surgery, Graduate School of Medicine, Kyungpook National University, Daegu, Korea
| | - Kyu Sang Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Mel S Lee
- Department of Orthopaedic Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Yun Jong Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital and Medical College of Seoul National University, Seongnam, Korea
| | - Michael A Mont
- Department of Orthopaedic Surgery, Lenox Hill Hospital, Northwell Health, New York, NY, USA
| | - Nobuhiko Sugano
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - John Taliaferro
- Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA
| | - Takuaki Yamamoto
- Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Dewei Zhao
- Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| |
Collapse
|
|
12
|
Paderno E, Zanon V, Vezzani G, Giacon TA, Bernasek TL, Camporesi EM, Bosco G. Evidence-Supported HBO Therapy in Femoral Head Necrosis: A Systematic Review and Meta-Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18062888. [PMID: 33808951 PMCID: PMC7999152 DOI: 10.3390/ijerph18062888] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/08/2021] [Accepted: 03/10/2021] [Indexed: 12/19/2022]
Abstract
Although many studies have shown that hyperbaric oxygen (HBO) therapy can significantly improve symptoms and quality of life of patients affected by femoral head necrosis, this therapy is not worldwide approved yet. This meta-analysis was performed to evaluate its clinical effect. Relevant studies published before May 2020 were systematically searched using terms related to HBO and femoral head necrosis. Fixed and random-effects models were used to estimate the odds ratio (OR) with 95% confidence intervals (CI). Subgroup analyses and publication bias tests were carried out to explore potential study heterogeneity and bias. Ten studies involving 353 controls and 368 HBO-treated cases were included, most of which were conducted on Asian population. The clinical effect in the HBO therapy group was 3.84 times higher than in the control group (OR = 3.84, 95% CI (2.10, 7.02), p < 0.00001). Subgroup analyses showed that the clinical effect of HBO therapy was statistically significant in the Asian subpopulation which represented most of the subjects (OR = 3.53, 95% CI (1.87, 6.64), p < 0.00001), but not in the non-Asian subpopulation, probably because of insufficient numerosity (OR = 7.41, 95% CI (0.73, 75.71), p = 0.09). The results of this meta-analysis suggest that patients with femoral head necrosis treated with HBO therapy can achieve a significant clinical improvement.
Collapse
Affiliation(s)
- Emma Paderno
- Environmental and Respiratory Physiology Lab and II Level Master in Diving and Hyperbaric Medicine, Department of Biomedical Sciences, University of Padova, 35122 Padova, Italy; (E.P.); (G.V.); (G.B.)
- DHMU at ICCB, Istituti Ospedalieri Bresciani, GSD—University and Research Hospitals, 25128 Brescia, Italy
| | - Vincenzo Zanon
- Environmental and Respiratory Physiology Lab and II Level Master in Diving and Hyperbaric Medicine, Department of Biomedical Sciences, University of Padova, 35122 Padova, Italy; (E.P.); (G.V.); (G.B.)
- DHMU at ICCB, Istituti Ospedalieri Bresciani, GSD—University and Research Hospitals, 25128 Brescia, Italy
- Correspondence: (V.Z.); (T.A.G.)
| | - Giuliano Vezzani
- Environmental and Respiratory Physiology Lab and II Level Master in Diving and Hyperbaric Medicine, Department of Biomedical Sciences, University of Padova, 35122 Padova, Italy; (E.P.); (G.V.); (G.B.)
| | - Tommaso Antonio Giacon
- Environmental and Respiratory Physiology Lab and II Level Master in Diving and Hyperbaric Medicine, Department of Biomedical Sciences, University of Padova, 35122 Padova, Italy; (E.P.); (G.V.); (G.B.)
- Correspondence: (V.Z.); (T.A.G.)
| | - Thomas L. Bernasek
- Adult Reconstruction, Florida Orthopaedic Institute, Tampa, FL 33625, USA;
| | | | - Gerardo Bosco
- Environmental and Respiratory Physiology Lab and II Level Master in Diving and Hyperbaric Medicine, Department of Biomedical Sciences, University of Padova, 35122 Padova, Italy; (E.P.); (G.V.); (G.B.)
| |
Collapse
|
|
13
|
Sun HS, Yang QR, Bai YY, Hu NW, Liu DX, Qin CY. Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing: A pilot study. World J Clin Cases 2020; 8:2530-2541. [PMID: 32607330 PMCID: PMC7322418 DOI: 10.12998/wjcc.v8.i12.2530] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 05/09/2020] [Accepted: 05/18/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Some gene loci such as complement C3d receptor 2 (CR2), nitric oxide synthase 3 (NOS3), collagen type II alpha 1 chain (COL2A1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were reported to be involved in this process.
AIM To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes.
METHODS SNVs in the CR2, NOS3, COL2A1, PTPN22, and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows–wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs.
RESULTS Six of the 49 patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S).
CONCLUSION The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2.
Collapse
Affiliation(s)
- Hong-Sheng Sun
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Qing-Rui Yang
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Yan-Yan Bai
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Nai-Wen Hu
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Dong-Xia Liu
- Department of Rheumatology and Immunology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| | - Cheng-Yong Qin
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China
| |
Collapse
|
|
14
|
Chang C, Greenspan A, Gershwin ME. The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis. J Autoimmun 2020; 110:102460. [PMID: 32307211 DOI: 10.1016/j.jaut.2020.102460] [Citation(s) in RCA: 144] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 12/28/2022]
Abstract
Corticosteroid associated osteonecrosis is bone death resulting from the use of chronic glucocorticoids and most commonly affects the femoral head, although the bones such as around knee joint, wrist joint and ankle joint can be affected. The pathogenesis is likely multifactorial, with genetic and environmental factors playing a role. Epigenetics may be the mechanism by which environment exerts it effects. In spite of recent discoveries, the exact pathogenesis of corticosteroid associated osteonecrosis is unknown. Over the past few years, more miRNA's have been found to be associated with osteonecrosis. The older mechanisms such as a coagulopathy, abnormalities in apoptosis and lipid metabolism dysfunction are still believed to play a role. The role of inflammatory pathways including the PDK1/AKT/mTOR signaling pathway, the PERK and Parkin pathways have been increasingly recognized as playing a mechanistic role. Histological damage to the joint can occur before the presence of symptoms. The most common symptoms are pain and an inability to bear weight. Differential diagnosis includes infection, bone marrow edema syndrome or subchondral fracture. Early detection is important for successful management of the condition. MRI is the best radiologic technique to diagnosis femoral head osteonecrosis. Multiple staging systems for osteonecrosis have been used over the years, including the Ficat and Arlet system and the Steinberg criteria. The later stages of these staging systems are irreversible. Both non-surgical (conservative) and surgical modes of therapy are used in the treatment of osteonecrosis.
Collapse
Affiliation(s)
- Christopher Chang
- Division of Pediatric Immunology and Allergy, Joe DiMaggio Children's Hospital, Hollywood, FL, 33021, USA; Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, Davis, CA, 95616, USA.
| | - Adam Greenspan
- Department of Radiology, University of California, Davis School of Medicine, Sacramento, CA, 95817, USA
| | - M Eric Gershwin
- Division of Pediatric Immunology and Allergy, Joe DiMaggio Children's Hospital, Hollywood, FL, 33021, USA.
| |
Collapse
|
|
15
|
Suyasa IK, Wiradewi Lestari AA. Low expression of vascular endothelial growth factor and high serum level of cyclic guanine monophosphate as the risk factors of femoral head osteonecrosis in alcohol-exposed Wistar rat. Chin J Traumatol 2020; 23:107-112. [PMID: 31980236 PMCID: PMC7156883 DOI: 10.1016/j.cjtee.2019.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 09/19/2019] [Accepted: 09/30/2019] [Indexed: 02/04/2023] Open
Abstract
PURPOSE Severe damage to the femoral head in patients with osteonecrosis has a high impact on morbidity. Despite early diagnosis, the treatment outcome is still unsatisfactory. This study aimed to explore the expression of vascular endothelial growth factor (VEGF) and cyclic guanine monophosphate (cGMP) serum level as the risk factors of femoral head osteonecrosis in alcohol-exposed Wistar rats. METHODS This was an experimental study using randomized post-test only control group design, with samples using 10-14 weeks Wistar male rats. Rats were then divided into 6 groups: 3 groups without intervention, and 3 groups with intervention using 40% alcohol given perorally. Each one group from intervention and control group was euthanized by the end of the week for 3 consecutive weeks. Proximal femurs were examined under microscope for osteonecrosis, immunohistochemically for VEGF, and blood serum for cGMP levels. RESULTS VEGF expression in the femoral head of alcohol-exposed Wistar rats was lower than those not exposed to alcohol (p < 0.005). Blood serum cGMP levels of alcohol-exposed Wistar rats were higher than those not exposed to alcohol (p < 0.005). The number of necrotic osteocytes in the femoral head of Wistar rats exposed to alcohol was greater than those not exposed to alcohol (p < 0.005). There are significant differences between VEGF, cGMP levels, and number of necrotic osteocytes in the control group and treatment at 1st, 2nd, and 3rd week (p < 0.005). CONCLUSIONS Based on the result of this study, VEGF and cGMP may be considered as diagnostic biomarkers for alcohol-induced femoral head osteonecrosis.
Collapse
Affiliation(s)
- I Ketut Suyasa
- Department of Orthopedic and Traumatology, Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Anak Agung Wiradewi Lestari
- Department of Clinical Pathology, Faculty of Medicine, Udayana University, Bali, Indonesia,Corresponding author.
| |
Collapse
|
|
16
|
CORR® ORS Richard A. Brand Award: Disruption in Peroxisome Proliferator-Activated Receptor-γ (PPARG) Increases Osteonecrosis Risk Through Genetic Variance and Pharmacologic Modulation. Clin Orthop Relat Res 2019; 477:1800-1812. [PMID: 31135556 PMCID: PMC7000017 DOI: 10.1097/corr.0000000000000713] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND The pathophysiology of osteonecrosis of the femoral head (ONFH) is poorly understood, and the diagnosis is idiopathic in as many as 40% of patients. Genetic and epigenetic etiologies have been postulated, yet no single nucleotide polymorphisms (SNPs) with intuitive biologic implications have been elucidated. QUESTIONS/PURPOSES (1) Do individuals with ONFH share common biologically relevant genetic variants associated with disease development? (2) What is the mechanism by which these SNPs may impact the expression or function of the affected gene or protein? METHODS This retrospective genome-wide association study (GWAS) evaluated participants from the Mayo Clinic Biobank and Mayo Clinic Genome Consortium between August 2009 and March 2017. We included every patient with atraumatic ONFH in each of these respective registries and every control patient in a previous GWAS with an acceptable platform to perform statistical imputation. The study was performed in two phases, with an initial discovery cohort and a subsequent validation cohort. The initial discovery cohort consisted of 102 patients with ONFH and 4125 controls. A logistic regression analysis was used to evaluate associations between SNPs and the risk of ONFH, adjusted for age and sex. Seven SNPs were identified in a gene of biological interest, peroxisome proliferator-activated receptor gamma (PPARG), which were then evaluated in a subsequent validation cohort of 38 patients with ONFH and 464 controls. Age, sex, race, and previous steroid exposure were similar between patients with ONFH and controls in both the discovery and validation cohorts. Separate from the two-phase genetic investigation, we performed targeted pharmacosurveillance to evaluate the risk association between the use of antidiabetic thiazolidinediones, a class of PPARG agonists, and development of ONFH by referencing 9,638,296 patient records for individuals treated at Mayo Clinic. RESULTS A combined analysis of the discovery and validation cohorts revealed that seven SNPs were tightly clustered adjacent to the 3' end of PPARG, suggesting an association with the risk of ONFH (p = 1.58 x 10-5.50 x10). PPARG gene-level significance was achieved (p = 3.33 x 10) when all seven SNPs were considered. SNP rs980990 had the strongest association with the risk of ONFH (odds ratio [OR], 1.95; 95% CI, 1.46-2.59; p = 5.50 x 10).The seven identified SNPs were mapped to a region near the PPARG gene and fell in a highly conserved region consisting of several critical transcription factor binding sites. Nucleotide polymorphisms at these sites may compromise three-dimensional chromatin organization and alter PPARG 3' end interactions with its 5' promoter and transcription start site. Pharmacosurveillance identified that patients who were exposed to thiazolidinediones had an increased relative risk of developing ONFH of 5.6 (95% CI, 4.5-7.1). CONCLUSIONS We found that disruption of PPARG regulatory domains is linked to an increased risk of ONFH. Mechanistically, aberrant regulation of PPARG compromises musculoskeletal differentiation because this master regulator creates a proadipogenic and antiosteogenic state. Furthermore, PPARG alters steroid metabolism and vasculogenesis, processes that are inextricably linked with ONFH. Pharmacologically, predisposition to ONFH was further exposed with thiazolidinedione use, which upregulates the expression of PPARG and is known to alter bone metabolism. Collectively, these findings provide a foundation to perform confirmatory studies of our proposed mechanism in preclinical models to develop screening diagnostics and potential therapies in patients with limited options. LEVEL OF EVIDENCE Level III, prognostic study.
Collapse
|
|
17
|
Etiologic Classification Criteria of ARCO on Femoral Head Osteonecrosis Part 1: Glucocorticoid-Associated Osteonecrosis. J Arthroplasty 2019; 34:163-168.e1. [PMID: 30348552 DOI: 10.1016/j.arth.2018.09.005] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 08/28/2018] [Accepted: 09/10/2018] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Glucocorticoid usage, a leading cause of osteonecrosis of the femoral head (ONFH), and its prevalence was reported in 25%-50% of non-traumatic ONFH patients. Nevertheless, there have been no unified criteria to classify glucocorticoid-associated ONFH (GA-ONFH). In 2015, the Association Research Circulation Osseous addressed the issue of developing a classification scheme. METHODS In June 2017, a task force was set up to conduct a Delphi survey concerning ONFH. The task force invited 28 experts in osteonecrosis/bone circulation from 8 countries. Each round of the Delphi survey consists of questionnaires, analysis of replies, and feedback reports to the panel. After 3 rounds of the survey, the panel reached a consensus on the classification criteria. The response rates were 100% (Round 1), 96% (Round 2), and 100% (Round 3), respectively. RESULTS The consensus on the classification criteria of GA-ONFH included the following: (1) patients should have a history of glucocorticoid use >2 g of prednisolone or its equivalent within a 3-month period; (2) osteonecrosis should be diagnosed within 2 years after glucocorticoid usage, and (3) patients should not have other risk factor(s) besides glucocorticoids. CONCLUSION Association Research Circulation Osseous established classification criteria to standardize clinical studies concerning GA-ONFH.
Collapse
|
|
18
|
Wang T, Azeddine B, Mah W, Harvey EJ, Rosenblatt D, Séguin C. Osteonecrosis of the femoral head: genetic basis. INTERNATIONAL ORTHOPAEDICS 2018; 43:519-530. [PMID: 30328481 DOI: 10.1007/s00264-018-4172-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2018] [Accepted: 09/18/2018] [Indexed: 12/19/2022]
Abstract
PURPOSE Genetic factors and hereditary forms of osteonecrosis of the femoral head (ONFH) have been elucidated through genetic association studies. The significance of these cases is that they suggest an alternative hypothesis to the development of the disease. This review presents a summary of single nucleotide polymorphisms (SNPs) and other genetic mutation variations found in association with ONFH, including our recent identification of a novel mutation in the transient receptor potential vanilloid 4 (TRPV4) gene in association with inherited ONFH. The purpose of this review is to consolidate and categorize genetic linkages according to physiological pathways. METHODS A systematic review of literature from PubMed and Google Scholar was undertaken with a focus on genetic linkages and hereditary case studies of the disease. Recent genetic analysis studies published after 2007 were the focus of genetic linkages in non-hereditary cases. RESULTS The summary of these genetic findings identifies biological processes believed to be involved in the development of ONFH, which include circulation, steroid metabolism, immunity, and the regulation of bone formation. CONCLUSION Taken together, these associations may lead to new pathways of bone repair and remodeling while opening new avenues for therapeutic targets. Knowledge of genetic variations could help identify individuals considered to be at higher risk of developing ONFH and prevent the multiple hit effect.
Collapse
Affiliation(s)
- Tracy Wang
- Vascular Biology Research lab, Research Institute (RI) McGill University Health Centre, C9 Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
| | - Bouziane Azeddine
- Vascular Biology Research lab, Research Institute (RI) McGill University Health Centre, C9 Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada
| | - Wayne Mah
- Vascular Biology Research lab, Research Institute (RI) McGill University Health Centre, C9 Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada
| | - Edward J Harvey
- Department Surgery, Division Orthopaedic Surgery, McGill University Health Centre, B5 Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada
| | - David Rosenblatt
- Department of Human Genetics, McGill University, Montreal, Quebec, Canada
| | - Chantal Séguin
- Vascular Biology Research lab, Research Institute (RI) McGill University Health Centre, C9 Montreal General Hospital, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada. .,Department of Medicine, Division of Hematology and Oncology, McGill University Health Centre, Montreal, Quebec, H4A 3J1, Canada. .,Glen Site, Cedars Cancer Centre, McGill University Health Centre, 1001 Décarie Blvd., room D02.7519, Montreal, Quebec, H4A 3J1, Canada.
| |
Collapse
|
|
19
|
Kao GS, Tu YK, Sung PH, Wang FS, Lu YD, Wu CT, Lin RLC, Yip HK, Lee MS. MicroRNA-mediated interacting circuits predict hypoxia and inhibited osteogenesis of stem cells, and dysregulated angiogenesis are involved in osteonecrosis of the femoral head. INTERNATIONAL ORTHOPAEDICS 2018; 42:1605-1614. [PMID: 29700584 DOI: 10.1007/s00264-018-3895-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Accepted: 03/13/2018] [Indexed: 01/07/2023]
Abstract
PURPOSE MicroRNAs (miRNAs) are associated with various pathologic conditions and can serve as diagnostic or therapeutic biomarkers. This study tried to identify the differentially expressed miRNAs to predict the possible pathomechanisms involved in osteonecrosis of the femoral head (ONFH). METHODS We compared the peripheral blood miRNAs in 46 patients with ONFH and 85 healthy controls by microarray and droplet digital polymerase chain reaction (ddPCR). Putative interacted networks between the differentially responded miRNAs were analyzed by web-based bioinformatics prediction tools. RESULTS Microarray identified 51 differentially expressed miRNAs with at least twofold change (upregulation in 34 and downregulation in 17), and the results were validated by ddPCR using six selected miRNAs. Bioinformatics genetic network analysis focusing on the six miRNAs found the upregulated miR-18a and miR-19a are associated with angiogenesis after induction of ischemia; the upregulated miR-138-1 can inhibit osteogenic differentiation of mesenchymal stem cells; the most targeted genes, p53 and SERBP1, are associated with hypoxia and hypofibrinolysis. CONCLUSIONS This study combined the miRNA analysis with the bioinformatics and predicts that hypoxia, inhibited osteogenesis of stem cells, and dysregulated angiogenesis might be orchestrated through the miRNA interacting circuits in the pathogenesis of ONFH.
Collapse
Affiliation(s)
- Gour-Shenq Kao
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan.,Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan
| | - Yuan-Kun Tu
- Department of Orthopedic Surgery, Eda Hospital, Kaohsiung, Taiwan
| | - Pei-Hsun Sung
- Division of Cardiology, Department of Internal Medicine, Kaohisung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan
| | - Feng-Sheng Wang
- Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan.,Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Taoyuan City, Taiwan
| | - Yu-Der Lu
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan
| | - Chen-Ta Wu
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan
| | - Rio L C Lin
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan.,Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan
| | - Hon-Kan Yip
- Division of Cardiology, Department of Internal Medicine, Kaohisung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan.
| | - Mel S Lee
- Department of Orthopedic Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niao-Sung, Kaohsiung, 833, Taiwan.
| |
Collapse
|
|
20
|
Wang Y, Yang X, Shi J, Zhao Y, Pan L, Zhou J, Wang G, Wang J. Combination analysis of NOS3, ABCB1 and IL23R polymorphisms with alcohol-induced osteonecrosis of the femoral head risk in Chinese males. Oncotarget 2018; 8:33770-33778. [PMID: 28422712 PMCID: PMC5464910 DOI: 10.18632/oncotarget.16809] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2016] [Accepted: 03/16/2017] [Indexed: 12/02/2022] Open
Abstract
Background Common variants of multiple genes played a crucial role in osteonecrosis of the femoral head (ONFH) onset which was proved by many previous reports. We hypothesized that polymorphisms in NOS3, ABCB1 and IL23R were related to individual differences in alcohol sensitivity and the development of alcohol-induced ONFH. Methods In this case-control study, we evaluated 8 SNPs in three genes in the Chinese Han population including 355 male cases and 355 healthy male controls. These SNPs were genotyped by Sequenom MassARRAY RS1000. To identify their relationship with alcohol-induced ONFH susceptibility using χ2 test and genetic model analysis. Results We found an association with alcohol-induced ONFH susceptibility for 4 SNPs (rs743506, rs3918184, rs13233308 and rs6693831) in three genes after adjusted by age. The genotype “G/A” of rs743506 in NOS3 gene acts as a risk factor in genotype (P = 0.003), dominant (P = 0.048), recessive (P = 0.005) and additive model(P = 0.006); The genotype “T/C” of rs3918184 in NOS3 gene acts as a risk factor in genotype (P = 0.012) and recessive model (P = 0.009); The genotype “T/C” of rs13233308 in ABCB1 gene acts as a risk factor in genotype (P = 0.038) and additive model(P = 0.041); The genotype “T/C” of rs6693831 in IL23R gene acts as a protective factor in genotype model (P = 0.046). Conclusions This study provides evidence for three alcohol-induced ONFH susceptibility genes (NOS3, ABCB1 and IL23R) in Chinese males and polymorphisms of them may be associated with alcohol-induced ONFH risk.
Collapse
Affiliation(s)
- Yuan Wang
- Department of Orthopedics, the People's Hospital of Manzhouli City, Manzhouli 021400, Inner Mongolia, China
| | - Xuejun Yang
- Department of Orthopedics, the Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia, China.,The College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia, China
| | - Jianping Shi
- The College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia, China
| | - Yan Zhao
- Department of Orthopedics, the Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia, China.,The College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia, China
| | - Linlin Pan
- Department of Orthopedics, the Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia, China.,The College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia, China
| | - Jinqiu Zhou
- Department of Endocrine, the 253th Hospital of People's Liberation Army of China, Hohhot 010010, Inner Mongolia, China
| | - Guoqiang Wang
- Department of Orthopedics, the Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia, China.,The College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia, China
| | - Jianzhong Wang
- Department of Orthopedics, the Second Affiliated Hospital, Inner Mongolia Medical University, Hohhot 010030, Inner Mongolia, China.,The College of Traditional Chinese Medicine, Inner Mongolia Medical University, Hohhot 010010, Inner Mongolia, China
| |
Collapse
|
|
21
|
Association of eNOS polymorphisms with susceptibility to osteonecrosis of the femur head : A meta-analysis. Z Rheumatol 2017; 76:267-273. [PMID: 27312465 DOI: 10.1007/s00393-016-0093-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVE The aim of the present study was to determine whether polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are associated with susceptibility to osteonecrosis of the femoral head (ONFH). METHODS We conducted a meta-analysis to assess the association between the 4b/a, G894T, and T786C polymorphisms of eNOS and the susceptibility to ONFH. RESULTS A total of five studies, which included 566 cases and 833 controls, were included in the meta-analysis. Meta-analysis revealed a significant association between allele a of the 4b/a polymorphism and ONFH in all study subjects (odds ratio, OR 3.237; 95 % confidence interval, CI 2.036-5.148; P = 6.9 × 10-7); stratification by ethnicity indicated an association between this allele and ONFH in Caucasians and Asians (OR 2.985; 95 % CI 1.592-5.597; P = 0.001 and OR 3.567; 95 % CI 1.793-7.095; P = 2.9 × 10-4, respectively). Meta-analysis stratified by ONFH type showed a significant association between allele a of the 4b/a polymorphism and idiopathic and secondary ONFH (OR 3.411; 95 % CI 2.049-5.679; P = 2.4 × 10-6 and OR 3.163; 95 % CI 1.781-5.619, P = 8.6 × 10 -5, respectively). However, the meta-analysis did not show any allelic association between the G894T and T786C polymorphisms and ONFH (OR 1.718; 95 % CI 0.796-3.707; P = 0.168 and OR 1.027; 95 % CI 0.191-5.517; P = 0.976, respectively). CONCLUSION Our meta-analysis of published studies shows that the 4b/a polymorphism is associated with the development of idiopathic and secondary ONFH in Caucasians and Asians.
Collapse
|
|
22
|
Khan AM, Choi J, Freiberg RA, Glueck CJ, Goldenberg N, Wang P. T786C Mutation in the Endothelial Nitric Oxide Synthase Gene in Patients With Primary Osteonecrosis. Orthopedics 2017; 40:e898-e903. [PMID: 28877324 DOI: 10.3928/01477447-20170824-03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2017] [Accepted: 07/31/2017] [Indexed: 02/03/2023]
Abstract
Mutations in the T786C endothelial nitric oxide synthase gene (eNOS) are associated with osteonecrosis and Prinzmetal's angina. Nitric oxide is necessary for bone health and ameliorates Prinzmetal's angina. This study compared mutations of T786C eNOS in 146 patients with primary osteonecrosis, 114 patients with Prinzmetal's angina, and 83 normal control subjects. Patients with osteonecrosis had more mutant eNOS alleles than control subjects (42% vs 22%, respectively; P<.0001) but had the same number of mutant alleles as patients with Prinzmetal's angina (42% vs 41%, respectively; P=.7), who in turn had more mutant eNOS alleles than control subjects (41% vs 22%, respectively; P=.0001). Of 146 patients with primary osteonecrosis, 65 (45%) had none of the 5 thrombophilias (Factor V Leiden heterozygosity, high levels of Factors VIII and XI, anticardiolipin antibody immunoglobulin M, and homocysteine) that otherwise distinguished patients with osteonecrosis from control subjects (P<.05). No associations were found between eNOS hetero-homozygosity and the 5 major thrombophilias in primary osteonecrosis. Of the 65 patients who had osteonecrosis but no major thrombophilias, for 41 (28% of the total sample of 146), eNOS hetero-homozygosity was the only abnormality. Normalization of nitric oxide levels with l-arginine 9 g/d or l-citrulline 800 mg/d, both of which relieve vasospastic angina in Prinzmetal's angina, which has the same eNOS genotype as primary osteonecrosis, may slow or stop the progression of osteonecrosis. Placebo-controlled trials of patients with primary osteonecrosis who are hetero-homozygous for the T786C eNOS mutation and have no major thrombophilias are needed to assess the safety and efficacy of this treatment. [Orthopedics. 2017; 40(5):e898-e903.].
Collapse
|
|
23
|
Wei BF, Feng Z, Wei W, Chen X. Associations of TNF-α -238 A/G and IL-10 -1082 G/A Genetic Polymorphisms With the Risk of NONFH in the Chinese Population. J Cell Biochem 2017; 118:4872-4880. [PMID: 28543357 DOI: 10.1002/jcb.26167] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Accepted: 05/23/2017] [Indexed: 02/06/2023]
Abstract
The study aims to explore the roles of common polymorphisms of Tumor Necrosis Factor-α (TNF-α) (-238 A/G and -308 A/G) and IL-10 (-819 T/C and -1082 G/A) genes in the risk of non-traumatic osteonecrosis of the femoral head (NONFH). One hundred and forty-seven NONFH patients and 135 healthy individuals were selected as the case and control groups. qRT-PCR and Western blotting techniques detected mRNA as well as protein expressions of TNF-α and IL-10 of each genotype in both the case and control groups. The GA genotype and the A allele of TNF-α -238 A/G were higher in the case group than in the control group. Compared with the control group, AA, GA, and AG + AA genotypes as well as the A allele of IL-10-1082 G/A were all lower in the case group. In the case groups increased levels of TNF-α as well as decreased levels of IL-10 expression when compared with the control group. TNF-α expression of TNF-α-238 GA genotype was significantly higher than that in patients with GG genotype, while the IL-10 expression of GA and AA genotypes of IL-10-1082 was significantly lower than in that of patients with the GG genotype. TNF-α protein expression in the GA genotype was significantly higher than in the GG genotype. In relation to TNF-α -238, TNF-α protein expression of GA and AA genotypes had significantly reduced more so than the GG genotype in IL-10-1082. TNF-α-238 A/G and IL-10-1082 G/A may be involved as risk factors of NONFH. J. Cell. Biochem. 118: 4872-4880, 2017. © 2017 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Biao-Fang Wei
- Department of Femoral Head, Linyi People's Hospital, Linyi, 276000, China
| | - Zhi Feng
- Department of Femoral Head, Linyi People's Hospital, Linyi, 276000, China
| | - Wei Wei
- Department of Orthopaedic, First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China
| | - Xiao Chen
- Department of Emergency, Women and Children's Health Care Hospital of Linyi, Linyi, 276016, China
| |
Collapse
|
|
24
|
Abstract
Younger patients are affected more often by osteonecrosis than by osteoarthritis, and osteonecrosis has significantly greater long-term morbidity. Corticosteroids are the most common cause of nontraumatic osteonecrosis. The femoral head is the most common site of osteonecrosis. In rare instances, osteonecrosis of the jaw has been associated with bisphosphonate exposure. This phenomenon is more common with repeated intravenous infusions of bisphosphonates. Case reports of osteonecrosis of the jaw in association with other medications, such as denosumab, have been reported. The final common pathway in the pathogenesis of osteonecrosis is disruption of blood supply to a segment of bone. Abnormalities in lipid metabolism, bone homeostasis, regulation of apoptosis, coagulopathies, innate immunity, and oxidative stress may play a role in the pathogenesis of osteonecrosis. Epigenetics may alter the predisposition to develop osteonecrosis. MRI is currently the optimal test for early diagnosis and identification of the extent of osteonecrosis. Nonsurgical treatment of osteonecrosis does not change the natural history of the disease. Although surgical treatment of femoral head osteonecrosis has many variations, most symptomatic patients eventually require total hip arthroplasty. Knowledge of risk factors and early detection are crucial to the successful management of osteonecrosis. Because of the lack of successful treatment options, new modes of management focus on the prevention of osteonecrosis.
Collapse
|
|
25
|
Carli A, Albers A, Séguin C, Harvey EJ. The Medical and Surgical Treatment of ARCO Stage-I and II Osteonecrosis of the Femoral Head: A Critical Analysis Review. JBJS Rev 2016; 2:01874474-201402000-00002. [PMID: 27490931 DOI: 10.2106/jbjs.rvw.m.00066] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Alberto Carli
- McGill University Health Center, Shriners Hospital for Children, 1529 Cedar Avenue, Montreal, Quebec, Canada H3G 1A6
| | - Anthony Albers
- McGill University Health Center, Shriners Hospital for Children, 1529 Cedar Avenue, Montreal, Quebec, Canada H3G 1A6
| | - Chantal Séguin
- McGill University Health Center, Department of Hematology and Oncology, Montreal General Hospital B7, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4
| | - Edward J Harvey
- McGill University Health Center, Montreal General Hospital B5, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4
| |
Collapse
|
|
26
|
Badhiwala JH, Nayiager T, Athale UH. The development of thromboembolism may increase the risk of osteonecrosis in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 2015; 62:1851-4. [PMID: 25931304 DOI: 10.1002/pbc.25553] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Accepted: 03/23/2015] [Indexed: 11/11/2022]
Abstract
Previous studies indicate pathophysiological and epidemiological parallels between osteonecrosis (ON) and thromboembolism (TE), two common treatment-related morbidities in acute lymphoblastic leukemia (ALL). To elucidate risk factors for ON and explore the relationship between ON and TE, we undertook a retrospective study of children (n = 208) with ALL. Twenty-one (10.1%) children developed ON and 42 (20.2%) TE on therapy. Thromboembolism was a significant predictor of ON on univariate (OR 8.85) and multivariate analysis, along with older age and PEGylated asparaginase. This observation supports a role for hypercoagulability in the pathogenesis of ON. Larger prospective studies are needed to further test these findings.
Collapse
Affiliation(s)
- Jetan H Badhiwala
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Trishana Nayiager
- Division of Hematology-Oncology, McMaster Children's Hospital, Hamilton Health Sciences, Hamilton, Ontario, Canada
| | - Uma H Athale
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.,Division of Hematology-Oncology, McMaster Children's Hospital, Hamilton Health Sciences, Hamilton, Ontario, Canada.,Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada
| |
Collapse
|
|
27
|
Choi HR, Steinberg ME, Y Cheng E. Osteonecrosis of the femoral head: diagnosis and classification systems. Curr Rev Musculoskelet Med 2015; 8:210-20. [PMID: 26088795 DOI: 10.1007/s12178-015-9278-7] [Citation(s) in RCA: 82] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Osteonecrosis of femoral head is a rare but disabling condition that usually results in progressive femoral head collapse and secondary arthritis necessitating total hip arthroplasty if not treated appropriately in early stages. However, early diagnosis is challenging as the onset of disease is insidious and the symptoms and signs are usually minimal and nonspecific until it becomes advanced. Of several diagnostic modalities, magnetic resonance imaging (MRI) is considered the imaging method of choice with the highest sensitivity and specificity, while detection of potential risk factors is very important as well. Many investigators have developed several different classification systems; however, there still is controversy regarding the optimal classification system. Diagnostic methods and the evolution of different classification systems will be reviewed in this paper.
Collapse
Affiliation(s)
- Ho-Rim Choi
- Department of Orthopaedic Surgery, University of Minnesota Medical School, 2450 Riverside Avenue, Minneapolis, MN, 55454, USA,
| | | | | |
Collapse
|
|
28
|
Silva PGDB, Ferreira Junior AEC, Teófilo CR, Barbosa MC, Lima Júnior RCP, Sousa FB, Mota MRL, Ribeiro RDA, Alves APNN. Effect of different doses of zoledronic acid in establishing of bisphosphonate-related osteonecrosis. Arch Oral Biol 2015; 60:1237-45. [PMID: 26093347 DOI: 10.1016/j.archoralbio.2015.05.015] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Revised: 05/13/2015] [Accepted: 05/24/2015] [Indexed: 10/23/2022]
Abstract
OBJECTIVES To establish osteonecrosis of the jaws in rats treated with different doses of zoledronic acid (ZA). METHODS Male Wistar rats (n=6-7) received three consecutive weekly intravenous ZA infusions at doses of 0.04, 0.20 or 1.00mg/kg ZA or saline (control). Four weeks after the last administration, the animals were submitted to simple extraction of the lower left first molar. An additional dose of ZA was administered seven days later, and the animals were sacrificed 28 days after exodontia. Weight was measured and blood was collected weekly for analysis. The jaw was radiographically and microscopically examined along with the liver, spleen, kidney and stomach. RESULTS All ZA doses showed a higher radiolucent area than the control (p<0.0001), but the dose of 0.04mg/kg did not show BRONJ. Doses of 0.20 and 1.00mg/kg ZA showed histological evidence of bone necrosis (p=0.0004). Anaemia (p<0.0001, r(2)=0.8073) and leucocytosis (p<0.0001, r(2)=0.9699) are seen with an increase of lymphocytes (p<0.0001, r(2)=0.6431) and neutrophils and monocytes (p=0.0218, r(2)=0.8724) in all the animals treated with an increasing dose of ZA. Haemorrhage and ectasia were observed in the spleen (p=0.0004) and stomach (p=0.0168) in a dose-dependent manner, and the animals treated with ZA showed a lower rate of weight gain (p<0.0001). CONCLUSIONS We designed a bisphosphonate-related osteonecrosis of the jaw model that reproduces radiographic and histological parameters and mimics clinical alterations such as leucocytosis, anaemia and idiosyncratic inflammatory post infusion reactions.
Collapse
Affiliation(s)
- Paulo Goberlânio de Barros Silva
- Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil.
| | - Antonio Ernando Carlos Ferreira Junior
- Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil
| | - Carolina Rodrigues Teófilo
- Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil
| | - Maritza Cavalcante Barbosa
- Department of Clinical Analysis, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil
| | | | - Fabrício Bitú Sousa
- Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil
| | - Mário Rogério Lima Mota
- Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil
| | | | - Ana Paula Negreiros Nunes Alves
- Department of Dental Clinic, Division of Oral Pathology, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceara, Fortaleza, Ceara, Brazil
| |
Collapse
|
|
29
|
Peng KT, Huang KC, Huang TW, Lee YS, Hsu WH, Hsu RWW, Ueng SWN, Lee MS. Single nucleotide polymorphisms other than factor V Leiden are associated with coagulopathy and osteonecrosis of the femoral head in Chinese patients. PLoS One 2014; 9:e104461. [PMID: 25119470 PMCID: PMC4131902 DOI: 10.1371/journal.pone.0104461] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2014] [Accepted: 07/09/2014] [Indexed: 12/25/2022] Open
Abstract
Single nucleotide polymorphisms (SNPs) of factor V Leiden have been associated with osteonecrosis of the femoral head (ONFH) in Caucasians but remains controversial in Asians. We used an SNP microarray to screen 55 loci of factor V gene in patients with ONFH of Chinese. Significantly different candidate SNPs at 14 loci were analyzed in 146 patients and 116 healthy controls using MALDI-TOF (matrix-assisted laser desorption/ionization time-of-flight) mass spectrometry and gene sequencing. The factor V Leiden (rs6025) was not found in all participants. Six SNP loci (rs9332595, rs6020, rs9332647, rs3766110, rs10919186, and rs12040141) were confirmed with significant differences in patients but not in controls. The rs6020 G-to-A polymorphism was found in 88.9% of the patients. In addition, a high percentage (87.6%) of the patients had an abnormal coagulation profile that included hyperfibrinogen, elevated fibrinogen degradation products, elevated D-dimer, abnormal protein S, abnormal protein C, or a decrease in anti-thrombin III. Patients with the rs6020 G-to-A polymorphism (mutation) had a higher risk (odds ratio: 4.62; 95% confidence interval: 1.44-14.8) of having coagulation abnormalities than did those without the mutation (wild-type) (χ(2) p = 0.006). Our findings suggested that the rs6020 polymorphism might be the genetic trait that accounts for the higher prevalence of ONFH in the Chinese population than in Westerners. Exposure to risk factors such as alcohol and steroids in patients with the rs6020 polymorphism causes coagulation abnormalities and, subsequently, thromboembolisms in the femoral head.
Collapse
Affiliation(s)
- Kou-Ti Peng
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kuo-Chin Huang
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Tsan-Wen Huang
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Yun-Shien Lee
- Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan
- Genomic Medicine Research Core Laboratory, Chang Gung Memorial Hospital, Taiwan
| | - Wei-Hsiu Hsu
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Robert W. W. Hsu
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Steve W. N. Ueng
- Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
| | - Mel S. Lee
- Department of Orthopaedic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan
- Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan
- Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- * E-mail:
| |
Collapse
|
|
30
|
The association of eNOS gene polymorphism with avascular necrosis of femoral head. PLoS One 2014; 9:e87583. [PMID: 24498338 PMCID: PMC3911980 DOI: 10.1371/journal.pone.0087583] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Accepted: 12/23/2013] [Indexed: 01/10/2023] Open
Abstract
Objectives Necrosis of femoral head is a severe pathological state with multiple etiologies. This study investigated the association of the 27-bp repeat polymorphism in intron 4 and G894T polymorphism in exon 7 of the endothelial nitric oxide synthase (eNOS) gene with the pathogenesis of avascular necrosis of femoral head (ANFH). Methods A total of 125 non-traumatic ANFH patients and 126 healthy controls were recruited for this study. The 27-bp repeat polymorphisms in intron 4 were analyzed by polymerase chain reaction (PCR) and sequencing. The G894T polymorphisms in exon 7 were analyzed by PCR– restriction fragment length polymorphism (PCR-RFLP) analysis. Results All alleles were observed in non-traumatic ANFH patients and control subjects. Both ANFH patients and idiopathic subgroup of ANFH patients showed higher frequency of the 4a/b genotype than controls (p = 0.001 and p = 0.020, respectively). Significantly higher frequency of G/T genotype was observed in ANFH patients and idiopathic subgroup of ANFH patients compared to controls (p = 0.009 and p = 0.035, respectively). Conclusion eNOS gene polymorphisms may be a risk factor for ANFH. The 27-bp repeat polymorphism in intron 4, G894T polymorphism in exon 7, and subsequently reduced eNOS activity may be involved in the etiology of idiopathic ANFH.
Collapse
|
|
31
|
Gómez-Puerta JA, Peris P, Reverter JC, Espinosa G, Martinez-Ferrer A, Monegal A, Monteagudo J, Tàssies D, Guañabens N. High prevalence of prothrombotic abnormalities in multifocal osteonecrosis: description of a series and review of the literature. Medicine (Baltimore) 2013; 92:295-304. [PMID: 24145698 PMCID: PMC4553995 DOI: 10.1097/md.0000000000000007] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Multifocal or multiple osteonecrosis (ON), defined by the involvement of 3 or more anatomic sites, is unusual, being observed in only 3%-10% of patients diagnosed with ON. We report the clinical characteristics of a cohort of 29 patients with multifocal ON from a single center and evaluate the prevalence of associated prothrombotic abnormalities in 26 of these patients. We conducted a retrospective study of all patients diagnosed with multifocal ON evaluated in our institution during the last 20 years. We recorded clinical manifestations and underlying diagnoses. A wide thrombophilic profile was performed, including antithrombin, protein C, protein S, lupus anticoagulant, anticardiolipin antibodies, activated protein C resistance, factor V Leiden, mutation G-20210-A of the prothrombin gene, and factor VIII. Coagulation test results were compared with those in a healthy control group and a group of patients with history of lower-extremity deep venous thrombosis. The mean age of the patients was 49.2 ± 15 years (range, 28-81 yr). The mean number of ON localizations per patient was 5.2 ± 2.3 (range, 3-11). Hips were the most commonly affected joint (82%), followed by knees (58%), shoulders (37%), and ankles (13%). Most patients had an underlying disease process, and 12 of 25 (48%) patients had coagulation test abnormalities. The most common alterations were high factor VIII levels and antiphospholipid antibody (aPL) positivity in 24% and 20% of cases, respectively. These abnormalities were more prevalent in patients with multifocal ON compared with patients in the control groups. Sixty-one percent of patients had a history of corticosteroid treatment. Patients with coagulation abnormalities had a higher number of ON localizations per patient (6.5 ± 2.7 vs. 3.88 ± 0.8; p = 0.002) and a higher prevalence of atypical ON localizations (25% vs. 0%; p = 0.05). In conclusion, in the present cohort of patients with multifocal ON, 48% of the patients had at least 1 prothrombotic factor, especially high levels of factor VIII and aPL. These findings have major implications for the diagnosis and treatment of multifocal ON and clearly indicate the need to perform a thrombophilic profile in these patients.
Collapse
Affiliation(s)
- Jose A Gómez-Puerta
- From the Department of Rheumatology (JAG-P, PP, AM-F, AM, NG), CIBERehd; and Hemotherapy and Haemostasis Service (JCR, JM, DT), Hospital Clínic, Barcelona; Department of Autoimmune Diseases (GE), Hospital Clínic, University of Barcelona, Barcelona, Spain; and Division of Rheumatology, Immunology and Allergy (JAG-P), Brigham and Women's Hospital, Boston, Massachusetts, United States
| | | | | | | | | | | | | | | | | |
Collapse
|
|
32
|
Kim HS, Bae SC, Kim TH, Kim SY. Endothelial nitric oxide synthase gene polymorphisms and the risk of osteonecrosis of the femoral head in systemic lupus erythematosus. INTERNATIONAL ORTHOPAEDICS 2013; 37:2289-96. [PMID: 23775455 DOI: 10.1007/s00264-013-1966-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 06/01/2013] [Indexed: 01/29/2023]
Abstract
PURPOSE Nitric oxide (NO), a short-lived gaseous free radical, is a potent mediator of biological responses involved in the pathogenesis of autoimmune rheumatic diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Nitric oxide also serves as an important signal in physiological processes, including angiogenesis, thrombosis, and bone turnover, which are known to be related to the pathogenesis of osteonecrosis. We investigated whether NOS3 gene polymorphisms are associated with risk of osteonecrosis of the femoral head (ONFH). METHODS Five polymorphisms in the NOS3 gene were genotyped using TaqMan assays in 306 controls, 150 SLE patients, and 50 SLE patients with ONFH (SLE_ONFH). RESULTS We found that Asp258Asp and Glu298Asp (G894T) polymorphisms in the NOS3 gene were significantly associated with risk of ONFH. Additionally, we calculated haplotype frequencies of a linkage disequilibrium (LD) block in NOS3 (rs1799983 - rs1800780) and tested for haplotype associations. The haplotypes G-A and T-A showed significant protective (P = 1.6 × 10(-3); OR 0.39, 95 % confidence intervals (CI) 0.22-0.7) and increased risk (P = 2.0 x 10(-5)-6.0 x 10(-4); OR 3.17-3.73) effects for ONFH, respectively. CONCLUSIONS These results suggest that exonic NOS3 polymorphisms may increase the risk of ONFH in Korean SLE patients.
Collapse
Affiliation(s)
- Hak Soo Kim
- Department of Orthopaedic Surgery, Graduate School of Medicine, Kyungpook National University, 130 Dongdeok-ro, Jung-gu, Daegu, 700-721, Korea
| | | | | | | |
Collapse
|
|
33
|
Endothelial nitric oxide synthase gene intron 4 polymorphism in non-traumatic osteonecrosis of the femoral head. INTERNATIONAL ORTHOPAEDICS 2013; 37:1381-5. [PMID: 23604198 PMCID: PMC3685672 DOI: 10.1007/s00264-013-1892-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2013] [Accepted: 03/30/2013] [Indexed: 11/02/2022]
Abstract
PURPOSE Nitric oxide (NO) synthesised by endothelial NO synthase (eNOS) is a potent regulator of internal haemodynamics. A polymorphism in intron 4 of the eNOS is associated with different vascular disorders. We investigated the potential involvement of this polymorphism in idiopathic and secondary osteonecrosis of the femoral head (ONFH) in Polish patients. METHODS We performed a study involving 68 patients with ONFH (45 idiopathic and 23 secondary) and 100 healthy controls. All subjects were genotyped for the eNOS4 polymorphism by the polymerase chain reaction followed by agarose gel electrophoresis. RESULTS The analysis revealed that the frequencies of eNOS4 genotypes were significantly different in ONFH patients (both idiopathic and secondary) than in controls. The frequencies of the 4a allele were significantly higher in the total group of patients versus controls [22.79 vs 9%, p = 0.00039, odds ratio (OR) 2.98]. In subgroup analysis the 4a allele increased significantly in both idiopathic (20 vs 9%, p = 0.0074, OR = 2.52) and secondary (28.26 vs 9%, p = 0.00047, OR = 3.98) ONFH patients compared to control subjects. The frequency of the 4a/b genotype in the total group of patients (36.76 vs 16%, p = 0.0011, OR = 3.24) as well as patients with idiopathic (35.56 vs 16%, p = 0.0069, OR = 2.96) and secondary (39.13 vs 16 %, p = 0.0073, OR = 3.89) ONFH was higher than in the control group. CONCLUSIONS There was a significantly higher frequency of eNOS 4a allele carriers among the total group of patients as well as in idiopathic and secondary ONFH. This suggests that the eNOS gene polymorphism may be associated with increased risk of ONFH.
Collapse
|
|
34
|
Gong LL, Fang LH, Wang HY, Peng JH, Si K, Zhu J, Han FF, Wang YH, Du GH, Pei LX, Liu LH. Genetic risk factors for glucocorticoid-induced osteonecrosis: a meta-analysis. Steroids 2013; 78:401-8. [PMID: 23357434 DOI: 10.1016/j.steroids.2013.01.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2012] [Revised: 12/11/2012] [Accepted: 01/11/2013] [Indexed: 12/17/2022]
Abstract
Glucocorticoid-induced osteonecrosis is a common and severe adverse event. We conducted a meta-analysis to investigate whether polymorphisms in target genes were associated with the risk of corticosteroid-induced osteonecrosis. Published literature from PubMed and EMBASE were searched for eligible publications. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a fixed- or random-effects model. There were 23 articles with 35 genes described the relationship between polymorphisms and glucocorticoid-induced osteonecrosis. Meta-analyses were carried out for those SNPs with three or more eligible studies, which included four SNPs located in three genes (PAI-1, MTHFR, ABCB1). The meta-analysis revealed that the PAI-1 4G allele was associated with an increased risk of osteonecrosis compared with the 5G allele (combined studies: OR=1.932, 95% CI=1.145-3.261). The OR for the 4G/4G vs. 5G/5G genotype of PAI-1 was 3.217 (95% CI 1.667-6.209 with combined studies), The relative risk of osteonecrosis was increased in the 4G allele vs. 5G/5G and 4G/4G genotype vs. 5G allele, with odds ratios of 2.304 (95% CI=1.235-4.299) and 2.307 (95% CI=1.527-3.485) in combined studies, respectively. The ABCB1 C3435T genotype distributions available confirmed that the C allele increased osteonecrosis risk compared with the T allele (OR 1.668, 95% CI=1.214-2.293) and TT genotype (OR 2.946, 95% CI=1.422-6.101). There was no evidence for significant association between MTHFR C677T and ABCB1 G2677T/A polymorphisms and risk of osteonecrosis. Results of this meta-analysis indicate that the PAI-1 4G/5G and ABCB1 C3435T polymorphisms may be risk factors for osteonecrosis.
Collapse
Affiliation(s)
- Li-Li Gong
- Beijing Chao-Yang Hospital, Affiliate of Capital Medical University, Beijing 100020, China.
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Carulli C, Innocenti M, Brandi ML. Bone vascularization in normal and disease conditions. Front Endocrinol (Lausanne) 2013; 4:106. [PMID: 23986744 PMCID: PMC3752619 DOI: 10.3389/fendo.2013.00106] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Accepted: 08/06/2013] [Indexed: 01/14/2023] Open
Abstract
Bone vasculature is essential for many processes, such as skeletal development and growth, bone modeling and remodeling, and healing processes. Endothelium is an integral part of bone tissue, expressing a physiological paracrine function via growth factors and chemokines release, and interacting with several cellular lines. Alterations of the complex biochemical interactions between vasculature and bone cells may lead to various clinical manifestations. Two different types of pathologies result: a defect or an excess of bone vasculature or endothelium metabolism. Starting from the molecular basis of the interactions between endothelial and bone cells, the Authors present an overview of the recent acquisitions in the physiopathology of the most important clinical patterns, and the modern therapeutic strategies for their treatments.
Collapse
Affiliation(s)
- Christian Carulli
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Massimo Innocenti
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Maria Luisa Brandi
- Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
- *Correspondence: Maria Luisa Brandi, Department of Surgery and Translational Medicine, University of Florence, Viale Pieraccini, 650139 Florence, Italy e-mail:
| |
Collapse
|
|
36
|
Abstract
Osteonecrosis affects younger patients more often than osteoarthritis and has significantly greater long-term morbidity. Corticosteroids constitute the most common cause of nontraumatic osteonecrosis. The femoral head is the most common site of osteonecrosis. Bisphosphonate use is associated with osteonecrosis of the jaw. The final common pathway in the pathogenesis of osteonecrosis is disruption of blood supply to a segment of bone. Abnormalities in lipid metabolism, bone homeostasis, regulation of apoptosis, coagulopathies, and oxidative stress may play a role in the pathogenesis of osteonecrosis. Magnetic resonance imaging is currently the optimal test for early diagnosis and identification of the extent of osteonecrosis. Nonsurgical treatment of osteonecrosis does not change the natural history of the disease. Although there are many variations on surgical treatment of femoral head osteonecrosis, most patients eventually require total hip arthroplasty. Knowledge of risk factors and early detection are crucial to the successful management of osteonecrosis. Due to the lack of successful treatment options, new modes focus on prevention of osteonecrosis.
Collapse
|
|
37
|
The pathogenesis of nontraumatic osteonecrosis. ARTHRITIS 2012; 2012:601763. [PMID: 23243507 PMCID: PMC3518945 DOI: 10.1155/2012/601763] [Citation(s) in RCA: 117] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2012] [Accepted: 10/28/2012] [Indexed: 12/13/2022]
Abstract
Nontraumatic osteonecrosis continues to be a challenging problem causing debilitating major joint diseases. The etiology is multifactorial, but steroid- and alcohol-induced osteonecrosis contribute to more than two thirds of all cases with genetic risk factors playing an important role in many other cases, especially when they contribute to hypercoagulable states. While the exact mechanisms remain elusive, many new insights have emerged from research in the last decade that have given us a clearer picture of the pathogenesis of nontraumatic osteonecrosis of the femoral head. Progression to end stage osteonecrosis of the femoral head appears to be related to four main factors: interactions involving the differentiation pathway of osteoprogenitor cells that promote adipogenesis, decreased angiogenesis, direct suppression of osteogenic gene expression and proliferation of bone marrow stem cells, and genetic anomalies or other diseases that promote hypercoagulable states.
Collapse
|
|
38
|
Takahashi S, Fukushima W, Kubo T, Iwamoto Y, Hirota Y, Nakamura H. Pronounced risk of nontraumatic osteonecrosis of the femoral head among cigarette smokers who have never used oral corticosteroids: a multicenter case-control study in Japan. J Orthop Sci 2012; 17:730-6. [PMID: 22927108 DOI: 10.1007/s00776-012-0293-x] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2012] [Accepted: 08/06/2012] [Indexed: 11/28/2022]
Abstract
BACKGROUND Cigarette smoking has been linked to an increased risk of nontraumatic osteonecrosis of the femoral head (ONFH) in previous studies. However, the effect of smoking amount, duration and cessation, and interaction with corticosteroids remains unclear. The purpose of this study was to precisely evaluate the effects of smoking and the interaction with corticosteroid use. METHODS This was a multicenter, matched case-control study in Japan. Cases were defined as patients who were newly diagnosed with ONFH at an initial visit or during the previous year if they were referred patients. For each case, matched controls were selected from patients without ONFH. The matching conditions were sex, age, and ethnicity. A logistic regression model was used to compute odds ratios (OR) and 95 % confidence intervals (95 % CI). RESULTS We compared 72 cases with 244 matched controls. ORs were 3.89 (95 % CI 1.46-10.4) for current smokers, 3.89 (1.22-12.4) for smokers consuming more than 20 cigarettes per day, 4.26 (1.32-13.7) for smokers with 26 pack-years or more, and 3.11 (0.92-11.5) for smokers with a history of 29 years or more, with significant or marginally significant dose-response relationships. OR for current smokers was 10.3 among those who had never used corticosteroids and 1.56 among past or current corticosteroid users (P for interaction 0.010). CONCLUSIONS Our results revealed that heavier cigarette smoking was associated with a higher risk of ONFH. The elevated risk from cigarette smoking was markedly pronounced among those who had never used oral corticosteroids.
Collapse
Affiliation(s)
- Shinji Takahashi
- Department of Public Health, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
| | | | | | | | | | | |
Collapse
|
|
39
|
Sekkat J, Rachidi O, Janani S, Mkinsi O. Idiopathic avascular necrosis of the femoral heads in five members of a Moroccan family. Joint Bone Spine 2012; 79:504-6. [DOI: 10.1016/j.jbspin.2012.06.012] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/25/2012] [Indexed: 11/24/2022]
|
|
40
|
Glueck CJ, Freiberg RA, Boriel G, Khan Z, Brar A, Padda J, Wang P. The role of the factor V Leiden mutation in osteonecrosis of the hip. Clin Appl Thromb Hemost 2012; 19:499-503. [PMID: 22696591 DOI: 10.1177/1076029612449901] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
We examined the hypothesis that the factor V Leiden (FVL) and G20101A prothrombin gene mutations are commonly associated with hip osteonecrosis. We prospectively evaluated 244 consecutively referred adults with osteonecrosis (ON), 161 idiopathic and 83 secondary. Cases (n = 244) did not differ from 104 normal controls by race. Of the 244 patients, 23 (9.4%) were FVL heterozygotes versus 2 of 104 controls (1.9%), P = .013, risk ratio (RR) = 4.90, 95% confidence interval (CI) 1.18 to 20.4. Of the 161 patients with idiopathic ON, 15 (9.3%) were FVL heterozygotes versus 2 of 104 normal controls (1.9%), P = .017, RR = 4.84, 95% CI 1.13 to 20.8. Of the 83 patients with secondary ON, 8 (9.6%) FVL heterozygotes versus 2 of 104 normal controls (1.9%), P = .024, RR = 5.01, 95% CI 1.09 to 23.0. Prothrombin gene heterozygosity in normal controls (2.9%) did not differ from ON cases (3.4%), P = 1.0. The thrombophilic FVL mutation is commonly associated with and may be pathoetiologic for hip osteonecrosis.
Collapse
Affiliation(s)
- Charles J Glueck
- 1Cholesterol Center, Jewish Hospital of Cincinnati, Cincinnati, OH, USA
| | | | | | | | | | | | | |
Collapse
|
|
41
|
Liu B, Cao Y, Wang D, Yao G, Bi Z. Vascular endothelial growth factor -634G/C polymorphism associated with osteonecrosis of the femoral head in a Chinese population. Genet Test Mol Biomarkers 2012; 16:739-43. [PMID: 22612467 DOI: 10.1089/gtmb.2011.0384] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
An impeded blood flow through the femoral head is incriminated in the etiopathogenesis of osteonecrosis of the femoral head (ONFH). Vascular endothelial growth factor (VEGF) is a strong angiogenic protein and also plays a role in the formation of cartilage and bone. The aim of this study was to evaluate the association of VEGF -634G/C polymorphism with ONFH in a Chinese population. A total of 220 unrelated patients with nontraumatic ONFH and 220 unrelated control subjects were consecutively enrolled in a hospital-based case-control study. A polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect the VEGF -634G/C genotype. Patients with ONFH had a significantly higher frequency of the CC genotype (odds ratio=1.64, 95% confidence interval=1.03, 2.60; p=0.04) than controls. There were no significant associations between any genotypes and the cause of ONFH. Our results support the hypothesis that the VEGF -634CC genotype is a risk factor of ONFH in the Chinese population. However, current results should be validated prospectively in larger cohorts.
Collapse
Affiliation(s)
- Bin Liu
- Department of Orthopedics, First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China
| | | | | | | | | |
Collapse
|
|
42
|
Abstract
OBJECTIVE To explore the clinical characteristics of osteonecrosis of the femoral head (ONFH) induced by steroids. METHODS From January 2000 to October 2009, 497 hips in 270 cases of ONFH induced by steroids were studied. A questionnaire was administered when the patients were admitted; the questions concerned the underlying disease, duration of steroid usage, total dosage of steroid, incubation period (time interval between commencement of steroid therapy and onset of pain), severity of pain, location of initial complaint, primary diagnosis, time lag from onset of pain to final diagnosis and physical signs when admitted. The correlations between pain and Association Research Circulation Osseous (ARCO) stage, bone marrow edema (BME) and lesion size were analyzed. RESULTS The median of time between commencing steroid medication and developing ONFH for the 269 cases was 18 months (range, 2-384 months). 78.82% cases presented with pain within three years of steroid initiation, only 10.41% patients first complained of pain six or more years after commencing steroid therapy. Fifty-six cases (20.82%) were misdiagnosed, lumbar disorders being the most frequent misdiagnoses. 79.29% of symptomatic hips presented with abnormal physical tests. Of 420 symptomatic hips, 166 hips were type C1, 223 hips type C2; 299 hips had collapsed; and there was BME in 209 hips. CONCLUSION Most patients with ONFH induced by steroids complained of pain within 3 years of commencing steroid therapy. Pain was associated with lesion size, collapse and BME. Atypical location of pain, failure to perform a physical examination and MRI findings were the main causes of misdiagnoses.
Collapse
Affiliation(s)
- Feng-chao Zhao
- Department of Orthopaedic Surgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.
| | | | | |
Collapse
|
|
43
|
Santovito A, Cervella P, Delpero M. Endothelial nitric oxide synthase intron 4 VNTR gene polymorphisms in European and African populations. Mol Biol Rep 2012; 39:6693-8. [DOI: 10.1007/s11033-012-1492-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2011] [Accepted: 01/24/2012] [Indexed: 01/05/2023]
|
|
44
|
Osteonecrosis of the femoral head: Surgical perspective. FORMOSAN JOURNAL OF SURGERY 2011. [DOI: 10.1016/j.fjs.2011.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
|
|
45
|
Kim HO, Cho CH, Cho YJ, Cho SH, Yoon KS, Kim KI. Significant associations of PAI-1 genetic polymorphisms with osteonecrosis of the femoral head. BMC Musculoskelet Disord 2011; 12:160. [PMID: 21752301 PMCID: PMC3156806 DOI: 10.1186/1471-2474-12-160] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2010] [Accepted: 07/14/2011] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The pathogenesis of osteonecrosis of the femoral head (ONFH) has been implicated in hypofibrinolysis and blood supply interruption. Previous studies have demonstrated that decreased fibrinolytic activity due to elevated plasminogen activator inhibitor-1 (PAI-1) levels correlates with ONFH pathogenesis. The -675 4G/5G single nucleotide polymorphism (SNP rs1799889) in the PAI-1 gene promoter is associated with PAI-1 plasma level. We investigated whether rs1799889 and two other SNPs of the PAI-1 gene (rs2227631, -844 G/A in the promoter; rs11178, +10700 C/T in the 3'UTR) are associated with increased ONFH risk. METHODS Three SNPs in PAI-1 were genotyped in 206 ONFH patients and 251 control subjects, using direct sequencing and a TaqMan® 5' allelic discrimination assay. We performed association analysis for genotyped SNPs and haplotypes with ONFH. RESULTS The 4G allele of rs1799889, A allele of rs2227631, and C allele of rs11178 were significantly associated with increased ONFH risk (p = 0.03, p = 0.003, and p = 0.002, respectively). When we divided the population according to gender, an association between the three SNPs and increased risk of ONFH was found only in men. In another subgroup analysis based on the etiology of ONFH, rs2227631 (A allele) and rs11178 (C allele) in the idiopathic subgroup (p = 0.007 and p = 0.021) and rs1799889 (4G allele) and rs11178 (C allele) in the alcohol-induced subgroup (p = 0.042 and p = 0.015) were associated with increased risk of ONFH. In addition, a certain haplotype (A-4G-C) of PAI-1 was also significantly associated with ONFH (p < 0.001). CONCLUSION Our findings demonstrated that three SNPs (rs1799889, rs2227631, and rs11178) of the PAI-1 gene were associated with ONFH risk. This study also suggests that PAI-1 SNPs may play an important role in ONFH.
Collapse
Affiliation(s)
- Hye- Ok Kim
- Department of Biochemistry and Molecular Biology (BK21 project), KyunHee University School of Medicine, Seoul, 130-701, Korea
| | | | | | | | | | | |
Collapse
|
|
46
|
Korompilias AV, Beris AE, Lykissas MG, Kostas-Agnantis IP, Soucacos PN. Femoral head osteonecrosis: why choose free vascularized fibula grafting. Microsurgery 2010; 31:223-8. [PMID: 21400578 DOI: 10.1002/micr.20837] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2010] [Accepted: 08/11/2010] [Indexed: 12/15/2022]
Abstract
Osteonecrosis of the femoral head is a disease in which bone death occurs and usually progresses to articular incongruity and subsequent osteoarthritis. To delay the process of the disease and the conversion to total hip arthroplasty, many surgical techniques have been described. Core decompression, nonvascularized autologous bone grafts, porous tantalum implant procedure, and various osteotomies have been used for the management of early precollapse stage osteonecrosis of the femoral head. However, none of these procedures is neither entirely effective nor can obtain predictable results. With the progress of microsurgery, the implantation of a free vascularized fibula graft to the necrotic femoral head has provided the most consistently successful results. Although the procedure is technically demanding, there is growing recognition that the use of free vascularized fibula graft may improve patient quality of life by functional improvement and pain alleviation. The success of the procedure is related to decompression of the femoral head, excision of the necrotic bone, and addition of cancellous bone graft with osteoinductive and osteoconductive properties, which augments revascularization and neoosteogenesis of the femoral head. Free vascularized fibula graft, especially in younger patients, is a salvaging procedure of the necrotic femoral head in early precollapse stages. In postcollapse osteonecrosis, the procedure appears to delay the need for total hip arthroplasty in the majority of patients. The purpose of this review article is to update knowledge about treatment strategies in femoral head osteonecrosis and to compare free vascularized fibula grafting to traditional and new treatment modalities.
Collapse
Affiliation(s)
- Anastasios V Korompilias
- Department of Orthopaedic Surgery, University of Ioannina, School of Medicine, Ioannina, Greece.
| | | | | | | | | |
Collapse
|
|
47
|
Nationwide epidemiologic survey of idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res 2010; 468:2715-24. [PMID: 20224959 PMCID: PMC2939331 DOI: 10.1007/s11999-010-1292-x] [Citation(s) in RCA: 250] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2009] [Accepted: 02/22/2010] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although numerous studies describe the clinical characteristics of idiopathic osteonecrosis of the femoral head (ONFH) in specific study populations, these have not been confirmed in countrywide studies. QUESTIONS/PURPOSES We therefore determined: (1) the annual number of patients seeking medical care and number of patients newly diagnosed; and (2) the distribution of the age and gender of the patients, potential causative factors, severity of the disease, and operative procedures performed. PATIENTS AND METHODS We conducted a nationwide epidemiologic survey in 2005. The survey included all orthopaedic departments in Japan by stratified random sampling according to the number of beds. RESULTS The number of patients who sought medical care for idiopathic ONFH during 2004 was estimated to be 11,400 (95% confidence interval, 10,100-12,800). We obtained clinical information from 1502 of these patients. The peak in age distribution occurred in the 40s. Potential causative factors were systemic steroid administration (51%) and habitual alcohol use (31%). Hip replacement was the most frequently performed procedure (65%). Among patients with a history of systemic steroid administration, systemic lupus erythematosus was reported most frequently (31%) as the underlying disease. Among patients younger than 40 years, steroid use was the most prominent potential causative factor (60%), and hip replacement frequently was performed (45%). A greater proportion of patients with no history of steroid or alcohol use was observed among patients 65 years or older (41%). CONCLUSIONS In addition to the disease burden of idiopathic ONFH in Japan, our results confirmed the importance of developing preventive and treatment strategies, especially among the younger population. LEVEL OF EVIDENCE Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
Collapse
|
|
48
|
T-786C polymorphism of the endothelial nitric oxide synthase gene and neuralgia-inducing cavitational osteonecrosis of the jaws. ACTA ACUST UNITED AC 2010; 109:548-53. [PMID: 20185342 DOI: 10.1016/j.tripleo.2009.11.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2009] [Revised: 10/29/2009] [Accepted: 11/03/2009] [Indexed: 11/24/2022]
Abstract
OBJECTIVE We hypothesized that, similar to idiopathic hip osteonecrosis, the T-786C mutation of the endothelial nitric oxide synthase (eNOS) gene affecting nitric oxide (NO) production was associated with neuralgia-inducing cavitational osteonecrosis of the jaws (NICO). DESIGN In 22 NICO patients, not having taken bisphosphonates, mutations affecting NO production (eNOS T-786C, stromelysin 5A6A) were measured by polymerase chain reaction. Two healthy normal control subjects were matched per case by race and gender. RESULTS Homozygosity for the mutant eNOS allele (TT) was present in 6 out of 22 patients (27%) with NICO compared with 0 out of 44 (0%) race and gender-matched control subjects; heterozygosity (TC) was present in 8 patients (36%) versus 15 control subjects (34%); and the wild-type normal genotype (CC) was present in 9 patients (36%) versus 29 controls (66%) (P = .0008). The mutant eNOS T-786C allele was more common in cases (20 out of 44 [45%]) than in control subjects (15 out of 88 [17%]) (P = .0005). The distribution of the stromelysin 5A6A genotype in cases did not differ from control subjects (P = .13). CONCLUSIONS The eNOS T-786C polymorphism affecting NO production is associated with NICO, may contribute to the pathogenesis of NICO, and may open therapeutic medical approaches to treatment of NICO through provision of L-arginine, the amino-acid precursor of NO.
Collapse
|
|
49
|
Kim TH, Hong JM, Shin ES, Kim HJ, Cho YS, Lee JY, Lee SH, Park EK, Kim SY. Polymorphisms in the Annexin gene family and the risk of osteonecrosis of the femoral head in the Korean population. Bone 2009; 45:125-31. [PMID: 19345290 DOI: 10.1016/j.bone.2009.03.670] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2008] [Revised: 03/10/2009] [Accepted: 03/17/2009] [Indexed: 10/20/2022]
Abstract
OBJECTIVE The pathogenesis of osteonecrosis of the femoral head (ONFH) probably reflects multiple etiologies. Recent studies have explored associations between genetic mutations and/or polymorphisms and ONFH. Annexins (ANXs) have been implicated in many physiological functions, including blood coagulation, inflammation, apoptosis, as well as Ca(2+) homeostasis in bone cells, all of which may be associated with ONFH. The aim of this study was to evaluate the possible association of AnnexinA (ANXA) family gene polymorphisms with ONFH. METHODS 52 SNPs from three genes of the ANXA family were selected from public databases and genotyped in 443 ONFH patients and 273 control subjects using the Affymetrix Targeted Genotyping 3 K Chip array. The association analysis of genotyped SNPs and haplotypes was performed with ONFH. RESULTS Among the polymorphisms tested of the ANXA family gene, the rs9324679, rs9324677, rs10037814, and rs11960458 SNPs of the ANXA6 gene were significantly associated with the risk of ONFH in all alternative analysis models (p range; 0.0007-0.049, odds ratio (OR); 0.63-1.72). Further analysis stratified by pathological etiology showed that these SNPs were also associated with the risk of ONFH in at least one subgroup (p range; 0.0017-0.049). Haplotype association analysis showed that several haplotypes were significantly associated with a risk of ONFH, with p values ranging between 0.0005 and 0.049 (OR range; 0.44-1.76). CONCLUSIONS These findings indicate that the polymorphisms of ANXA6 are associated with ONFH. Thus, these polymorphisms may be useful genetic markers to identify high-risk individuals.
Collapse
Affiliation(s)
- Tae-Ho Kim
- Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Jung-gu, Daegu, Republic of Korea
| | | | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Osteonecrosis of the femoral head in patients with type 1 human immunodeficiency virus infection: clinical analysis and review. Clin Rheumatol 2009; 28:815-23. [DOI: 10.1007/s10067-009-1156-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2008] [Revised: 02/16/2009] [Accepted: 02/25/2009] [Indexed: 02/06/2023]
|