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BACKGROUND: Up to now, there is no literature on the relationship between blood laboratory tests and the course of nontraumatic osteonecrosis of femoral head in different stages. It is necessary to further explore and analyze so as to better clarify the influencing factors of nontraumatic osteonecrosis of femoral head. OBJECTIVE: To analyze the relationship between blood laboratory indicators and the course of nontraumatic osteonecrosis of the femoral head by the Association Research Circulation Osseous (ARCO), thus exploring the influencing factors of blood laboratory indicators on the course of nontraumatic osteonecrosis of the femoral head. METHODS: This study used a retrospective study design. A total of 2 103 patients with osteonecrosis of the femoral head were retrieved from Wangjing Hospital of China Academy of Chinese Medical Sciences database, and 1 075 patients with nontraumatic osteonecrosis of the femoral head were ultimately included based on inclusion and exclusion criteria. Patient age, gender, body mass index, and blood laboratory test results were collected. Blood laboratory tests included low-density lipoprotein, total cholesterol, triglycerides, high-density lipoprotein, apolipoprotein β, apolipoprotein α1, uric acid, total protein quantitative, alkaline phosphatase, activated partial thromboplastin time, prothrombin time, prothrombin time International Normalized Ratio, prothrombin time activity, fibrinogen quantitative, coagulation time of thrombin, D-dimer, total iron binding capacity, and platelet count. The indicators of patients with different age groups and different ARCO stages were compared, and multiple Logistic regression analysis was applied to explore the influencing factors of ARCO stages in osteonecrosis of the femoral head. RESULTS AND CONCLUSION: (1) There were statistical differences in total cholesterol, uric acid, prothrombin time, prothrombin time International Normalized Ratio, and D-dimer among ARCO stages in the young group (P < 0.05). Among young patients in ARCO stage II, total cholesterol levels were higher than those in ARCO stage III (P < 0.05). Uric acid levels in ARCO stage IV were higher than those in ARCO stage II and III (P < 0.05). Prothrombin time and prothrombin time International Normalized Ratio were shorter in ARCO stage IV and II than in ARCO stage III (P < 0.05). D-dimer levels were higher in ARCO stage III and IV than in ARCO stage II (P < 0.05). (2) There were statistically significant differences in high-density lipoprotein, coagulation time of thrombin, and D-dimer among ARCO stages in the middle-aged group (P < 0.05). Among middle-aged patients in ARCO stage IV, high-density lipoprotein levels were higher than those in ARCO stages II and III (P < 0.05). Coagulation time of thrombin was shorter in ARCO stage IV than in ARCO stage III (P < 0.05). D-dimer levels were higher in ARCO stages IV than in ARCO stages II and III (P < 0.05). (3) The uric acid, activated partial thromboplastin time, D-dimer, and platelet count in the elderly group showed statistically significant differences (P < 0.05). The uric acid level in ARCO stage IV was higher than that in ARCO stage II and III patients in the elderly group (P < 0.05), while the activated prothrombin time in ARCO stage II patients was shorter than that in ARCO stage III patients in the elderly group (P < 0.05). The D-dimer level in ARCO stage III and IV patients was higher than that in ARCO stage II patients in the elderly group (P < 0.05). The platelet count in ARCO stage IV was lower than that in ARCO stage III patients in the elderly group (P < 0.05). (4) Multiple logistic regression analysis showed that total cholesterol and platelet count may be protective factors for course of nontraumatic osteonecrosis of the femoral head, while D-dimer, uric acid, overweight, and young and middle age may be risk factors for course of nontraumatic osteonecrosis of the femoral head. (5) It is indicated that total cholesterol, high-density lipoprotein, uric acid, prothrombin time, prothrombin time International Normalized Ratio, and D-dimer are statistically significant among patients with different ARCO stages. Total cholesterol and platelet count may be protective factors for the course of nontraumatic osteonecrosis of the femoral head, while D-dimer, uric acid, overweight, and middle-aged and young age groups may be hazard factors for the course of nontraumatic osteonecrosis of the femoral head. [ABSTRACT FROM AUTHOR]

This study is to probe into the meaning of serum miR-532-5p in nontraumatic osteonecrosis of the femoral head (ONFH), and a molecular mechanism of miR-532-5p in the development of nontraumatic ONFH. This study enrolled 96 patients diagnosed with nontraumatic ONFH and 96 patients with femoral neck fracture. The levels of miR-532-5p, ABL1, MMP-3, MMP-13, and cleaved-caspase3 were determined. Radiographic progression was assessed by ARCO staging system. Visual analog scale (VAS) and Harris hip score (HHS) were employed for evaluation of the symptomatic severity of nontraumatic ONFH. Cell viability and apoptosis in chondrocytes isolated from clinical samples were investigated with CCK-8 and flow cytometry. The levels of lactic dehydrogenase (LDH), superoxide dismutase (SOD), and malondialdehyde (MDA), mitochondrial membrane potential (ΔΨm), and reactive oxygen species (ROS) were determined. miR-532-5p was downregulated in tissues and serum of patients with nontraumatic ONFH, negatively related with ARCO staging and VAS, and positively correlated with HHS. Cell apoptosis, LDH, MDA, and ROS strengthened, while cell viability, ΔΨm, and SOD reduced in chondrocytes of nontraumatic ONFH patients. ABL1 was upregulated in cartilage tissues from nontraumatic ONFH patients. miR-532-5p targeted ABL1, and overexpressed miR-532-5p alleviated nontraumatic ONFH-induced oxidative stress damage of chondrocytes by restraining ABL1. miR-532-5p ameliorated oxidative stress injury in nontraumatic ONFH by inhibiting ABL1.

BACKGROUND: Nontraumatic osteonecrosis of the femoral head is a group of diseases characterized by progressive worsening of hip pain and dysfunction, which seriously endangers human health. Its pathogenesis, early diagnosis and treatment remain a major challenge for clinical orthopedic surgeons. OBJECTIVE: Using isobaric tags for relative and absolute quantitation technology, proteomics was used to screen key proteins that may be associated with nontraumatic osteonecrosis of the femoral head. Analysis of the expression characteristics and potential biological functions of these proteins laid the foundation for further research on the etiology and molecular mechanisms of nontraumatic osteonecrosis of the femoral head. METHODS: Serum proteins were extracted from nontraumatic osteonecrosis of the femoral head patients and healthy humans, and then labeled using isobaric tags for relative and absolute quantitation technology. Liquid chromatography combined with tandem mass spectrometry was performed to separate and analyze the peptides. Differentially expressed proteins were obtained through identifying and quantifying the proteins using Proteome Discoverer 2.1 software and analyzed via GO annotation, KEGG pathway annotation, and functional enrichment clustering analysis. RESULTS AND CONCLUSION: (1) A total of 137 differentially expressed proteins were obtained from 1 006 proteins identified by mass spectrometry, of which the expression of 54 and 83 proteins was up-regulated and down-regulated, respectively. (2) The differentially expressed proteins associated with the development of nontraumatic osteonecrosis of the femoral head included apolipoprotein B, apolipoprotein A2, apolipoprotein E, complement C4 and C7, etc. (3) The analysis results of KEGG signaling pathway enrichment showed that the major signaling pathways of key targets comprised p53 signaling pathway, transcriptional growth factor β signaling pathway, and dilated cardiomyopathy signaling pathway. It is concluded that apolipoproteins were closely related to nontraumatic osteonecrosis of the femoral head. This study provides insight into the molecular mechanisms underlying nontraumatic osteonecrosis of the femoral head. [ABSTRACT FROM AUTHOR]

Abstract Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. Methods To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes. Results The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1. Conclusions This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.

Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. Methods: A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. Results: NONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, χ2 = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, χ 2 = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. Conclusions: Our findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.

Objective: Decreased adiponectin (APN) levels have been detected in patients with osteonecrosis of the femoral head (ONFH). The scope of this study was aimed to explore the relationship between serum APN levels and disease severity in nontraumatic ONFH patients. Patients and methods: Ninety two nontraumatic ONFH patients and 92 healthy controls were enrolled for this study following the estimation of sample size. Serum APN concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The radiographic progression was determined by Ficat grading system. The clinical severity was evaluated by visual analog scale (VAS), Harris hip scores (HSSs) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores. Results: Serum APN levels were significantly lower in ONFH patients than in healthy controls. Serum APN levels were significantly lower in patients with Ficat stage 4 ONFH than in patients with stage 3 ONFH, and APN levels in patients with stage 3 were lower compared with stage 2. Serum APN levels were negatively correlated with the Ficat grading system. In addition, serum APN levels were also negatively related to VAS and WOMAC scores and positively associated with HSSs. Conclusion: Decreased serum APN levels may reflect disease severity of nontraumatic ONFH. [ABSTRACT FROM AUTHOR]

Background: Collapse of the femoral head associated with nontraumatic osteonecrosis (NOFH) is one of the most common causes of disability in young adult patients. Excessive bone resorption by osteoclast coincident with the suppression of osteogenesis are believed to be responsible for collapse progression. Alendronate that inhibits bone resorption by inducing osteoclast apoptosis has been traditionally used for treating NOFH; however, several reports documented serious complications by the use of this drug. On the other hand, teriparatide activates osteoblasts leading to an overall increase in bone volume, and is expected to reduce the progression of femoral head collapse in NOFH. Therefore, the present study was undertaken to examine pharmacological effects of teriparatide on collapse progression of NOFH and to compare these effects with alendronate.Methods: We conducted a retrospective study in our facility for comparing the pharmacological effects of teriparatide and alendronate on 32 NOFH patients diagnosed with osteoporosis. Between 2007 and 2013, patients were treated with daily administration of 20 μg teriparatide (15 patients: 18 hips), or with 35 mg of alendronate once a week (17 patients: 22 hips). The mean period of follow-up was 18.7 months. The progression of collapse was evaluated prior to the administration and later every three months by anteroposterior radiographs. Collapse progression with > 1 mm was defined as advanced collapse, while with < 1 mm was defined as stable radiologic disease. Student's t-test and the chi-square test was used to do compare the pharmacological effects of the two groups.Results: Treatment with terparatide had a tendency to reduce the rate of advanced collapse as compared to that with alendronate (p = 0.105). Kaplan-Meier curves related to stable radiologic disease showed that teriparatide-treated patients had better stable states than these treated with alendronate (p = 0.08, log-rank test). Moreover, treatment with teriparatide resulted in a significant reduction in collapse progression as compared to that with alendronate, noted at the end of follow-up period (p = 0.049).Conclusion: The present study suggests that teriparatide has greater pharmacological effects than alendronate for treating NOFH and preventing the collapse of femoral head.Trial Registration: The registration number in UMIN Clinical Trial Registry is UMIN000017582 . The date of registration is May 5, 2015. [ABSTRACT FROM AUTHOR]

Introduction: Risk factors for nontraumatic osteonecrosis of the femoral head have in common that they trigger intravascular coagulation and thus lead to devascularization of the femoral head. In part of the patients, however, no risk factors seem to be evident. Mechanical reasons contributing to nontraumatic osteonecrosis have not been discussed so far. We hypothesized that recurrent traumatization of the vessels supplying the femoral head by a cam-type mechanism as in femoroacetabular impingement could add to intravascular coagulation. We, therefore, asked whether structural abnormalities at the femoral head-neck junction indicative of such a mechanism could be observed in radiographs of patients with osteonecrosis of the femoral head. Materials and methods: The preoperative anteroposterior and lateral radiographs of 77 patients who underwent surgery because of osteonecrosis of the femoral head were retrospectively screened for a reduced head-neck offset by measuring the α-angle. For comparison, the α-angle was measured on anteroposterior and lateral radiographs of 339 control subjects without evident underlying hip pathology. Results: The mean α-angle was 62.8° (SD 18.7°) for anteroposterior and 67.6° (SD 13.2°) for lateral radiographs in patients with nontraumatic osteonecrosis of the femoral head, whereas in control subjects, the mean α-angle was 47.2° (SD 9.6°) ( p < 0.0001) and 47.6° (SD 10.3°) ( p < 0.0001), respectively. Conclusions: A reduced head-neck offset in patients with nontraumatic osteonecrosis of the femoral head may act as a mechanical (co-)factor in developing osteonecrosis of the femoral head. [ABSTRACT FROM AUTHOR]

Objective: Decreased adiponectin (APN) levels have been detected in patients with osteonecrosis of the femoral head (ONFH). The scope of this study was aimed to explore the relationship between serum APN levels and disease severity in nontraumatic ONFH patients., Patients and Methods: Ninety two nontraumatic ONFH patients and 92 healthy controls were enrolled for this study following the estimation of sample size. Serum APN concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The radiographic progression was determined by Ficat grading system. The clinical severity was evaluated by visual analog scale (VAS), Harris hip scores (HSSs) and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scores., Results: Serum APN levels were significantly lower in ONFH patients than in healthy controls. Serum APN levels were significantly lower in patients with Ficat stage 4 ONFH than in patients with stage 3 ONFH, and APN levels in patients with stage 3 were lower compared with stage 2. Serum APN levels were negatively correlated with the Ficat grading system. In addition, serum APN levels were also negatively related to VAS and WOMAC scores and positively associated with HSSs., Conclusion: Decreased serum APN levels may reflect disease severity of nontraumatic ONFH., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Collapse of the femoral head associated with nontraumatic osteonecrosis (NOFH) is one of the most common causes of disability in young adult patients. Excessive bone resorption by osteoclast coincident with the suppression of osteogenesis are believed to be responsible for collapse progression. Alendronate that inhibits bone resorption by inducing osteoclast apoptosis has been traditionally used for treating NOFH; however, several reports documented serious complications by the use of this drug. On the other hand, teriparatide activates osteoblasts leading to an overall increase in bone volume, and is expected to reduce the progression of femoral head collapse in NOFH. Therefore, the present study was undertaken to examine pharmacological effects of teriparatide on collapse progression of NOFH and to compare these effects with alendronate., Methods: We conducted a retrospective study in our facility for comparing the pharmacological effects of teriparatide and alendronate on 32 NOFH patients diagnosed with osteoporosis. Between 2007 and 2013, patients were treated with daily administration of 20 μg teriparatide (15 patients: 18 hips), or with 35 mg of alendronate once a week (17 patients: 22 hips). The mean period of follow-up was 18.7 months. The progression of collapse was evaluated prior to the administration and later every three months by anteroposterior radiographs. Collapse progression with > 1 mm was defined as advanced collapse, while with < 1 mm was defined as stable radiologic disease. Student's t-test and the chi-square test was used to do compare the pharmacological effects of the two groups., Results: Treatment with terparatide had a tendency to reduce the rate of advanced collapse as compared to that with alendronate (p = 0.105). Kaplan-Meier curves related to stable radiologic disease showed that teriparatide-treated patients had better stable states than these treated with alendronate (p = 0.08, log-rank test). Moreover, treatment with teriparatide resulted in a significant reduction in collapse progression as compared to that with alendronate, noted at the end of follow-up period (p = 0.049)., Conclusion: The present study suggests that teriparatide has greater pharmacological effects than alendronate for treating NOFH and preventing the collapse of femoral head., Trial Registration: The registration number in UMIN Clinical Trial Registry is UMIN000017582 . The date of registration is May 5, 2015.