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ObjectiveTo explore the therapeutic mechanism of Bushen Huoxue prescription from the perspective of bone metabolism by observing the clinical efficacy of this prescription in treating femoral head necrosis (ONFH, syndrome of liver and kidney deficiency) and its influences on bone metabolism indexes: N-terminal propeptide (PINP) and β-collagen degradation product (β-CTX). MethodSixty-six ONFH patients with the syndrome of liver and kidney deficiency in Zhengzhou Traditional Chinese Medicine Hospital of Orthopedics from December 2021 to September 2022 were selected. The patients were randomized into an experimental group and a control group by the parallel control method, with 33 patients in each group. The experimental group received Bushen Huoxue prescription orally, while the control group received Xianlinggubao Capsules orally, with a treatment cycle of 6 months. The visual analogue scale (VAS) score, Harris score, Association Research Circulation Osseous (ARCO) staging, imaging changes, quantitative scores of TCM symptoms, and serum levels of PINP and β-CTX were determined before and after treatment. The occurrence of adverse events and reactions was recorded. ResultThe total response rate in the experimental group was 83.87% (26/31), which was higher than that (68.75%, 22/32) in the control group (Z=-2.096, P<0.05). After treatment, the single and total scores of TCM symptoms, VAS score, and β-CTX level decreased in the two groups (P<0.05). Moreover, the decreases in the scores of hip pain, lower limb mobility, soreness of waist and knees, and lower limb flaccidity, total score of TCM symptoms, VAS score, and β-CTX level in the experimental were larger than those in the control group (P<0.05). After treatment, the imaging results showed no significant improvement in the two groups. The Harris score and PINP level in both groups increased after treatment (P<0.05), and the increases were more obvious in the experimental group than in the control group (P<0.05). No serious adverse event or adverse reaction appeared during the observation period. ConclusionBushen Huoxue prescription can relieve pain and TCM symptoms and improve the hip joint function in treating ONFH patients with the syndrome of liver and kidney deficiency. It can inhibit the development of ONFH, increase PINP, and decrease β-CTX. No obvious side effect appears during the clinical observation period, which shows that Bushen Huoxue prescription has good safety.
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Objective To investigate the risk factors of femoral head necrosis after internal fixation of fem-oral neck fracture,and to clarify the predictive role of serological index plasminogen activator inhibitors-1(PAI-1)on femoral head necrosis.Methods A total of 95 patients undergoing internal fixation for femoral neck fracture were included in the study.Relevant clinical information of patients was obtained and the serum PAI-1 levels of the patients before surgery,1,2,and 3 days after surgery were detected.After 1-year follow-up,patients were divided into necrosis group and non-necrosis group according to the occurrence of femoral head necrosis.Visual Analog Scale(VAS),Western Ontario McMaster University Osteoarthritis Index(WOMAC),and Harris Hip Score(HHS)were conducted in all patients one year after the surgery.The differences of basic clinical information and serum PAI-1 levels before and after the surgery between necrosis group and non-necrosis group were compared,and Logistic regression analysis was performed to identify the relevant risk factors for femoral head necrosis.The relationships between the PAI-1 level after operation and the VAS,WOMAC,and HHS scores of patients were figured out.The receiver operating characteristic(ROC)curve of serum PAI-1 as a predictive indicator for femoral head necrosis was drawn to clarify its predictive val-ue.Results Garden classification and reduction quality between the necrosis group and the non-necrosis group were risk factors for femoral head necrosis(P<0.05).The serum PAI-1 at 1 day and 2 days after surgery in the necrosis group were significantly higher than that in the non-necrosis group(P<0.05).The level of PAI-1 at 1 day and 2 days after surgery was positively correlated with VAS and WOMAC(P<0.05),and negative-ly correlated with HHS(P<0.05).Logistic regression analysis showed that the increase of serum PAI-1 level at 1 day and 2 days after surgery were risk factors for femoral head necrosis(P<0.05).The ROC curve showed that serum PAI-1 level at 2 days after surgery had higher predictive value than that at 1 day after sur-gery,and the cut-off value was 44.8 ng/L,the sensitivity was 68.49%,the specificity was 86.36%,and the ar-ea under the curve(AUC)was 0.807.Conclusion The serum PAI-1 level at 1 day and 2 days after internal fixation of femoral neck fracture could be used to predict the occurrence of femoral head necrosis,especially the serum PAI-1 levels at 2 days after surgery.
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From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.
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BACKGROUND:Piezo1,a mechanosensitive protein,is tightly connected to osteogenic differentiation,and it has been demonstrated that TAZ has a role in regulating osteogenic differentiation.It is unclear whether TAZ participates in the regulation of osteogenic differentiation of human bone marrow mesenchymal stem cells by Piezo1,so it is crucial to investigate its unique mechanism to prevent osteonecrosis of the femoral head. OBJECTIVE:To elucidate what function Piezo1 plays in osteogenic differentiation and TAZ expression in human bone marrow mesenchymal stem cells. METHODS:The siRNA targeting Piezo1 was constructed and transfected into 293T cells.The silencing efficiency was detected by RT-qPCR.The selected Piezo1-Home-2337 was packaged according to the silencing efficiency,and its optimal multiplicity of infection value was assayed by immunofluorescence staining.The packaged Piezo1 silencing recombinant lentivirus was transfected into human bone marrow mesenchymal stem cells,and its silencing effect was detected by RT-qPCR and western blot assay.Alizarin red staining,alkaline phosphatase activity analysis,immunofluorescence staining,RT-qPCR and western blot assay were utilized to analyze the effect of silencing Piezo1 on the osteogenic differentiation of human bone marrow mesenchymal stem cells. RESULTS AND CONCLUSION:(1)The mRNA and protein levels of Piezo1 in human bone marrow mesenchymal stem cells transfected by si-Piezo1 were decreased significantly,with a statistically significant difference compared with normal and negative control groups.(2)The alkaline phosphatase activity in the si-Piezo1 group was much lower and the calcium deposition in the si-Piezo1 group was significantly reduced compared with the negative control group.(3)The mRNA levels of osteogenesis-related genes including Runt-related transcription factor 2(Runx2),osteopontin(OPN),distal-less homeobox 5(DLX5),osteocalcin,β-catenin and Tafazzin(TAZ)in the si-Piezo1 group were significantly decreased compared with the negative control group.Afterward,the expression levels of TAZ and β-catenin protein in the si-Piezo1 group were down-regulated significantly compared with the negative control group,whereas the expression levels of p-TAZ and p-β-catenin protein in the si-Piezo1 group had the opposite condition.(4)The results of immunofluorescence staining showed that the expression of TAZ and β-catenin in human bone marrow mesenchymal stem cells in the si-Piezo1 group was less compared with the negative control group.(5)These findings indicate that Piezo1 can promote the osteogenic differentiation of human bone marrow mesenchymal stem cells.The osteogenic ability of human bone marrow mesenchymal stem cells is significantly reduced after silencing Piezo1,and the expression of TAZ is also reduced.
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BACKGROUND:Compound Shengmai Chenggu capsule has good therapeutic effects on early steroid-induced osteonecrosis of the femoral head,but the exact mechanism of treatment is not fully understood. OBJECTIVE:To observe the effect of compound Shengmai Chenggu capsule on fucosyltransferase 8,osteogenic gene and Wnt/β-catenin in bone tissue of rats with steroid-induced osteonecrosis of the femoral head. METHODS:Sixty Sprague-Dawley rats were randomized into blank group,model group,low-,middle-,and high-dose drug groups(n=12 per group).In the latter four groups,animal models of steroid-induced osteonecrosis of the femoral head were established by subcutaneous injection of imiquimod(once every 2 weeks,2 times in total)and gluteal muscle injection of methylprednisolone(once a week,4 times in total).The low-,middle-and high-dose drug groups were given 1.89,3.78 and 7.56 g/kg per day compound Shengmai Chenggu capsule solution by gavage respectively on the second day after the last modeling.The same amount of saline was given by gavage to the model group.Administration lasted 8 weeks.After the administration,micro-CT scan,histological staining,compression test,RT-qPCR and western blot were performed on the femoral head. RESULTS AND CONCLUSION:Micro-CT scan results showed that compared with the blank group,trabecular volume fraction,trabecular number and trabecular thickness were significantly decreased(P<0.05),while trabecular separation was increased in the model group(P<0.05).Compared with the model group,the compound Shengmai Chenggu capsule could increase trabecular volume fraction,trabecular number and trabecular thickness(P<0.05),and decrease trabecular separation(P<0.05)in a dose-dependent manner.Hematoxylin-eosin staining results showed that compared with the model group,the rate of empty bone lacunae was reduced in a dose-dependent group in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups(P<0.05).Immunohistochemical staining results showed that compared with the blank group,the protein expression of fucosyltransferase 8,Runx2 and bone morphogenetic protein 2 was reduced in the model group(P<0.05);compared with the model group,the compound Shengmai Chenggu capsule increased the protein expression of fucosyltransferase 8,Runx2 and bone morphogenetic protein 2 in a dose-dependent manner(P<0.05).Results from the compression test showed that there was a dose-dependent increase in the maximum load and elastic modulus of the femoral head in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups compared with the model group(P<0.05).RT-qPCR and western blot results showed that the mRNA and protein expressions of fucosyltransferase 8,Runx2,alkaline phosphatase,osteocalcin,osteoblast-specific transcription factor and bone morphogenetic protein 2 were decreased in the model group compared with the blank group(P<0.05);compared with the model group,there was a dose-dependent increase in the mRNA and protein expressions of the above indicators in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups compared with the model group(P<0.05).Compared with the blank group,the mRNA and protein expression of Wnt2,low-density lipoprotein receptor-related protein 5 and β-catenin were decreased(P<0.05)and the mRNA and protein expressions of glycogen synthase kinase 3β were increased(P<0.05)in the model group;compared with the model group,there was a dose-dependent increase in the mRNA and protein expressions of Wnt2,low-density lipoprotein receptor-related protein 5 and β-catenin(P<0.05)but a dose-dependent decrease in the mRNA and protein expressions of lycogen synthase kinase 3β(P<0.05)in the low-,middle-,and high-dose compound Shengmai Chenggu capsule groups.To conclude,the mechanism by which the compound Shengmai Chenggu capsule treats steroid-induced osteonecrosis of the femoral head may activate the Wnt/β-catenin signaling pathway through the up-regulation of fucosyltransferase 8,thereby promoting bone formation.
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BACKGROUND:At present,it is found that both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology can repair damaged blood vessels,promote vascular regeneration,rebuild blood supply in the femoral head,restore normal blood supply,and further promote osteogenesis.Both of them have certain advantages in early intervention of steroid-induced necrosis of femoral head.It can also further understand the mechanism of blood activating and stasis removing herbs and platelet-rich plasma technology in improving steroid-induced necrosis of the femoral head,and provide new ideas for future treatment. OBJECTIVE:To review the research progress of the mechanism of the combination of blood activating and blood stasis removing herbs and platelet-rich plasma technology on steroid-induced necrosis of the femoral head according to the related literature at home and abroad. METHODS:PubMed,Web of Science,Metstr,CNKI and WanFang databases were searched for relevant articles."Traditional Chinese medicine,signal pathways,steroid induced necrosis of femoral head,vascular endothelial growth factor,platelet rich plasma"were used as the Chinese and English search terms separately.The time limit for searching the literature was from January 2000 to July 2022,and 75 related articles were finally included. RESULTS AND CONCLUSION:Both Chinese medicine for activating blood circulation and removing blood stasis and platelet-rich plasma technology have certain advantages in intervening the early stage of steroid-induced necrosis of femoral head.For traditional Chinese medicine,both single and compound drugs can effectively alleviate the further development of steroid-induced necrosis of the femoral head.The specific mechanism is as follows:(1)The traditional Chinese medicine for activating blood circulation and removing blood stasis has a significant anticoagulation effect,which can antagonize the abnormal(hypercoagulable)state of blood caused by hormone drugs,and further restore the normal blood supply in the femoral head.(2)Traditional Chinese medicine for activating blood circulation and removing blood stasis can repair damaged vascular endothelium,regenerate blood vessels and remodel blood supply in the femoral head by activating vascular endothelial growth factor.(3)The traditional Chinese medicine of promoting blood circulation and removing blood stasis has the obvious effect of removing blood stasis,which can reduce the accumulation of fat cells in the bone marrow cavity and relieve the pressure in the femoral head.(4)Traditional Chinese medicine for promoting blood circulation and removing blood stasis can regulate relevant signal pathways,maintain bone metabolism,promote the differentiation and balance of osteoblasts and osteoclasts,and effectively reduce steroid-induced necrosis of the femoral head.In addition,platelet-rich plasma contains a large amount of high concentration of cell growth factor,which plays a positive role in osteogenesis and vascular regeneration,and can also improve the abnormal state of the blood.Traditional Chinese medicine for activating blood circulation and removing blood stasis combined with platelet-rich plasma technology can play their biological roles,and the intervention effect is more significant.
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BACKGROUND:After the internal fixation of cannulated screws in femoral neck fractures,because the affected limb is often unable to bear weight in the short term and the implants with high stiffness have a stress shielding effect on the fracture end,it is easy to cause osteoporosis of the affected limb and changes in the biomechanical distribution of the proximal femur,the incidence of osteonecrosis of the femoral head is high after surgery.At present,few studies have been conducted on the biomechanical effects of osteoporosis at the proximal end of the femur occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws. OBJECTIVE:Using finite element analysis,to investigate the biomechanical effects of osteoporosis occurring after femoral neck fracture surgery on femoral neck fracture treated with cannulated screws and explore the role of biomechanical factors in osteonecrosis of the femoral head. METHODS:Based on the obtained CT scan data of the femur in a patient with a femoral neck fracture,a proximal femoral model for internal fixation for femoral neck fracture was established by Mimics 19.0,3-Matic,UG 11.0,Hypermesh 14.0,and Abaqus software.One finite element model of the proximal femur without osteoporosis and three finite element models of the proximal femur with osteoporosis were analyzed using Abaqus software.The stress,contact pressure,displacement peak and cloud map under different components of the four models were measured and analyzed,and the internal stress changes and distribution of the femoral head were compared and analyzed. RESULTS AND CONCLUSION:The stresses and contact pressures of the femoral head and lower anterior cannulated screws varied more with the degree of osteoporosis.The peak displacement of the four models increased slowly with the degree of osteoporosis.By one-way analysis of variance,there was no significant effect of the degree of osteoporosis on the peak stress,contact pressure,and displacement of the different components.The internal stress distribution of the femoral head changed with the degree of osteoporosis.Changes in the biomechanical environment of the proximal femur have an important impact on osteonecrosis of the femoral head.
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BACKGROUND:For non-traumatic osteonecrosis of the femoral head,if the femoral head collapses,it will have a great impact on the normal life of the patients.Thus,it is necessary to use an appropriate way to evaluate the risk of femoral head collapse and then to take targeted measures to delay the process of femoral head collapse. OBJECTIVE:To analyze the natural course of early osteonecrosis of the femoral head(without collapse)under different locations of necrotic lesions. METHODS:121 patients(191 hips)with early non-traumatic osteonecrosis of the femoral head who were treated in the Outpatient Department of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017 were enrolled in this study.The clinical data of all patients were followed up for 5 years to observe the collapse of osteonecrosis of the femoral head and the risk coefficient of femoral head collapse among different JIC types.The collapse rate of osteonecrosis of the femoral head was calculated during the follow-up. RESULTS AND CONCLUSION:(1)A total of 191 hips were included in this study.The femoral head collapsed in 86 hips during follow-up,with a total collapse rate of 45.0%.Among the influencing factors,age,ARCO stage and JIC classification were the main influencing factors of femoral head collapse(P<0.05),but body mass index,sex,incidence side and pathogenic factors were not the main influencing factors(P>0.05).(2)Among 191 hips,in JIC classification,the total collapse rates of type A,type B,type C1 and type C2 were 11.1%(2/18),30.2%(16/53),52.4%(43/82),and 65.8%(25/38),respectively.There were significant differences in the total collapse rate of the femoral head among all types(P<0.05).The collapse risk results showed that the collapse risk of type B,type C1 and type C2 was 2.41,5.22 and 7.89 times higher than that of type A,respectively.(3)Both JIC classification and ARCO stage were correlated with femoral head collapse(P<0.01).There was no significant difference in the collapse rate of the femoral head among all JIC types in ARCO I stage hips(P>0.05).In the hips with ARCO II stage,the collapse rates of the femoral head of JIC types A,B,C1 and C2 were 1.2%,19.5%,50.0%and 29.3%,respectively,and there were significant differences in the collapse rates among different types(P<0.05).(4)During follow-up,the collapse rates of the femoral head in the first to fifth years were 29.3%,7.9%,4.7%,2.6%and 0.5%,respectively.(5)Results showed that for early non-traumatic osteonecrosis of the femoral head,the risk of collapse of osteonecrosis of the femoral head is high within one year,and the location of the focus of osteonecrosis affects the risk of collapse of the femoral head.The effect of the location of the focus on the prognosis of the disease should be considered in clinical treatment.
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OBJECTIVE:The rabbit model of steroid-induced osteonecrosis of femoral head is the most commonly used animal model of femoral head necrosis.The pathological changes of the femoral head are close to clinical practice,however,the conditions,methods and evaluation standards of animal models reported in and outside China are not uniform,which leads to the low scientific value of animal models and is difficult to popularize.This study aimed to clarify the influence of different mold-making conditions on the establishment of steroid-induced osteonecrosis of femoral head rabbit model and analyze the appropriate conditions for the successful model establishment. METHODS:We searched the CNKI,WanFang,VIP,CBM,WoS,PubMed and EMbsae databases for the literature on the modeling of steroid-induced osteonecrosis of femoral head rabbits up to April 1,2022,completed the screening of the literature according to the inclusion and exclusion criteria and literature quality evaluation,and extracted the outcome index data in the literature.RevMan Stata and ADDIS statistical software were used to conduct a meta-analysis of the included data. RESULTS:(1)A total of 82 articles with 1 366 rabbits were included in the study.The steroid-induced osteonecrosis of femoral head modeling methods were divided into three types:steroid-alone method,steroid combined lipopolysaccharide method and steroid combined serum method.Among these,33 articles used steroid-alone method;20 articles used steroid combined lipopolysaccharide method;29 articles used steroid combined serum method.(2)Meta-analysis results showed that the three modeling methods significantly increased the rate of empty bone lacunae in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001),and significantly decreased the ratio of the trabecular bone area in the femoral head of steroid-induced osteonecrosis of femoral head rabbits(P<0.001).The order of empty bone lacunae rate of each modeling method was:steroid combined with lipopolysaccharide method>steroid-alone method>steroid combined with serum method>normal group,and the order of trabecular bone area rate of each modeling method was:normal group>steroid combined with serum method>steroid-alone method>steroid combined with lipopolysaccharide method.(3)The results of subgroup analysis suggested that the rate of empty bone lacunae in the rabbit model induced by steroid alone might be related to the rabbit variety and the type of steroid used for modeling(difference between groups P<0.05),in which the combined effect amount of New Zealand white rabbits was higher than that of Chinese white rabbits(P<0.05)and Japanese white rabbits,and the combined effect amount of dexamethasone was higher than that of other steroids.The rate of empty bone lacunae induced by steroid combined with lipopolysaccharide was related to the administration mode of lipopolysaccharide and the type of steroid(P<0.05),among which the combined effect of methylprednisolone sodium succinate was significantly higher than that of other steroids(P<0.05),and the combined effect of prednisolone was significantly lower than that of other steroids(P<0.05).The combined effect of lipopolysaccharide 100 μg/kg×twice was significantly lower than 10 μg/kg×twice and 50 μg/kg×twice(P<0.05).The rate of empty bone lacunae in the model induced by steroid combined with serum was related to serum dose and steroid type(P<0.05),among which the combined effect amount of dexamethasone sodium phosphate was significantly higher than other steroid types(P<0.05),and the combined effect amount of dexamethasone was significantly lower than other steroid types(P<0.05);the combined effect amount of serum"10 mL/kg+6 mL/kg"combined dose was lower than other serum doses(P<0.05). CONCLUSION:(1)With the rate of empty bone lacunae and the ratio of trabecular bone area as the judgment standard for the successful establishment of the model,the three modeling methods can successfully construct the rabbit steroid-induced osteonecrosis of femoral head model,of which the steroid combined with lipopolysaccharide method is the best.(2)New Zealand white rabbits and dexamethasone are recommended when selecting the steroid-alone method.Methylprednisolone sodium succinate and low-dose lipopolysaccharide are recommended when selecting the steroid combined with lipopolysaccharide method.Dexamethasone sodium phosphate is recommended when selecting the steroid combined with serum modeling method.
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BACKGROUND:Most scholars now believe that children with cerebral palsy who have severe spinal deformities in early childhood(<15 years of age)may have a higher risk of progression of spinal deformities,which may result from imbalances in movement due to pelvic tilt,pain,etc. OBJECTIVE:To investigate the relationship between lumbar spine development and hip joint development in children with spastic cerebral palsy. METHODS:A retrospective analysis was performed in 102 children with spastic cerebral palsy admitted at Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine from January 2014 to December 2021.All admitted children had X-rays of the pelvic position and the lumbar lateral position.Anteroposterior X-ray of the pelvis was performed to measure femoral head migration percentage,central edge angle,neck-shaft angle,and acetabular index.The sagittal Cobb angle,sacral slope,arch-top distance,and lumbar lordosis index were measured by the lateral X-ray of the lumbar spine.Correlation of the two sets of indicators was further analyzed.All children were divided into normal group,risk group,hip subluxation group and total hip dislocation group according to their femoral head migration percentage,and the differences in lumbar spine indexes between groups were evaluated. RESULTS AND CONCLUSION:Pearson correlation analysis showed that the femoral head migration percentage was moderately positively correlated with sagittal Cobb angle and arch-top distance,and weakly positively correlated with lumbar lordosis index;the central edge angle was moderately negatively correlated with the arch-top distance and weakly negatively correlated with the sagittal Cobb angle;the neck-shaft angle was weakly positively correlated or not correlated with the sagittal Cobb angle and lumbar lordosis index;and the acetabular index was weakly positively correlated with the sagittal Cobb angle and arch-top distance.No statistically significant correlation was found between the remaining indicators.According to the femoral head migration percentage,the children were divided into four groups,including 25 cases in the normal group,41 cases in the risk group,27 cases in the hip subluxation group,and 9 cases in the total hip dislocation group.The sagittal Cobb angle was significantly increased in the risk group,the hip subluxation group and the total hip dislocation group compared with the normal group,showing an increasing trend group by group,and there were significant differences between groups(P<0.05).Compared with the normal group,the lumbar lordosis index in the risk group and the hip subluxation group increased significantly,and there were significant differences between groups(P<0.05).There was an increase trend in the lumbar lordosis index of the total hip dislocation group compared with the normal group.Compared with the normal group,the arch-top distance in the hip subluxation group and the total hip dislocation group increased significantly(P<0.05),and there was a stepwise increasing trend.There was no significant difference in sacral slope between groups.To conclude,the development of the lumbar spine in children with cerebral palsy is closely related to the development of the pelvic hip joint,and the most obvious relationship is between lumbar lordosis and hip dislocation.
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BACKGROUND:Osteonecrosis of the femoral head is a common orthopedic disease,and hip preservation surgery with bone grafting is commonly used in the early stage,in which autologous bone and allograft bone are commonly used as bone grafting materials.However,autologous bone transplantation is highly traumatic and bone supply is limited,and allograft bone is rich in sources,but there are serious risks of immune rejection and absorption.In recent years,the tissue engineering technique based on mesenchymal stem cells is a new method for the treatment of femoral head necrosis,which is gradually widely used after basic experiments and clinical application. OBJECTIVE:To review the application and prospect of tissue engineering in the treatment of osteonecrosis of the femoral head to provide a new choice for the clinical treatment of osteonecrosis of the femoral head. METHODS:The PubMed database and CNKI database from 2013 to 2023 were searched by the first author with Chinese and English search terms"tissue engineering,mesenchymal stem cells,biological scaffolds,cytokines,osteonecrosis of the femoral head,bone graft,hip preservation".The articles on the treatment of osteonecrosis of the femoral head with tissue engineering technology were selected,and 55 representative articles were included for review after the initial screening of all articles according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)With the continuous development of biotechnology and materials science,great progress has been made in the treatment of osteonecrosis of the femoral head by bone tissue engineering,such as the application of gene-modified mesenchymal stem cells to repair osteonecrosis,the combination of gene recombination technology and surface modification technology with bone tissue engineering in the treatment of osteonecrosis of the femoral head.(2)When applied to the necrotic femoral head,tissue engineering technology can promote the regeneration of necrotic bone tissue and the repair of the vascular system,provide biomechanical stability for the necrotic area,and use bioactive factors to accelerate the repair of seed cells to complete the regeneration of new bone in necrotic area.(3)However,most of these studies are still in the animal experiment stage,and there are still many unsolved problems and challenges in bone tissue engineering research.With the rapid development of nanotechnology,tissue engineering and clinical medicine,biomimetic replacement bone grafting materials with perfect performance are expected to come into being.(4)In the future,bone tissue engineering for osteonecrosis of the femoral head is expected to be a satisfactory treatment for patients with hip preservation.
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BACKGROUND:Artificial femoral head replacement is an effective method for the treatment of elderly unstable intertrochanteric fractures.However,the effect of lesser trochanter reconstruction in femoral head replacement for Evans-Ⅲ femoral intertrochanteric fractures has not been reported. OBJECTIVE:To analyze the effect of lesser trochanter reconstruction on the outcome of artificial femoral head replacement with long stem in elderly patients with Evans-Ⅲ femoral intertrochanteric fracture. METHODS:A retrospective analysis was performed on medical records of 45 elderly patients who underwent bipolar long-stem artificial femoral head replacement due to Evans-Ⅲ femoral intertrochanteric fractures in the Department of Bone and Joint Surgery,Second Affiliated Hospital of Xi'an Jiaotong University from June 2017 to May 2021.According to whether the small trochanter was reconstructed during surgery(reduction and fixation),they were divided into the reconstruction group(n=25)and the non-reconstruction group(n=20).The operation time,bleeding volume,time of getting out of bed,hospital stay time,Harris scores at 3 and 6 months postoperatively,and the incidence of complications during follow-up were compared between the two groups. RESULTS AND CONCLUSION:(1)The operation time of the reconstruction group was longer(99.72±13.41 minutes)than that of the non-reconstruction group(88.90±16.53 minutes)(t=2.369,P=0.023),and there were no significant differences in bleeding volume,time of getting out of bed or hospital stay time between the two groups(P>0.05).(2)The Harris score of the reconstruction group(69.06±5.64 points)was higher than that of the non-reconstruction group(63.35±5.93 points)at 3 months postoperatively(t=2.982,P=0.005).At 6 months postoperatively,the Harris score of the reconstruction group(86.67±4.49 points)was higher than that of the non-reconstruction group(82.34±5.68 points)(t=2.782,P=0.009).(3)In addition,no significant difference existed in the incidence of complications between the reconstruction and non-reconstruction groups(χ2=0.008,P=0.927).(4)It is concluded that in elderly patients with Evans-Ⅲ femoral intertrochanteric fractures,lesser trochanter reconstruction in the artificial femoral head replacement significantly improved postoperative hip function despite increased operative time,demonstrating the importance of the lesser trochanter reconstruction in the artificial femoral head replacement for Evans-Ⅲ intertrochanteric fractures in the elderly people.
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BACKGROUND:It is known that N6-methyladenosine(m6A)plays a role in the pathogenesis of various diseases and studies have suggested its involvement in the pathologic changes of steroid-induced femoral head necrosis(SNFH).However,research on m6A methylation modifications in steroid-induced femoral head necrosis is limited. OBJECTIVE:Using bioinformatics methods to identify the differential expression of m6A-related genes in steroid-induced femoral head necrosis and to predict miRNAs associated with these genes to further elucidate the role and mechanism of m6A methylation in steroid-induced femoral head necrosis. METHODS:Differential gene expression between steroid-induced femoral head necrosis and control groups was analyzed using GSE123568 gene expression data and identified using the"limma"package in R.Functional enrichment analysis was performed on the differentially expressed genes.Differential analysis of the related genes was carried out using the"ggstatsplot"package in R.The differential genes were cross-validated using the GSE74089 dataset.An mRNA-miRNA regulatory network was constructed,and co-expression analysis was performed on the module genes followed by enrichment analysis.Differences in immune cell infiltration between steroid-induced femoral head necrosis and control groups were quantified using the ssGSEA method. RESULTS AND CONCLUSION:Correlation analysis revealed 13 m6A-related genes,and further analysis through the protein-protein interaction network identification and receiver operating characteristic curve analysis showed that YTHDF2 was expected to be a core differential gene as a potential early biomarker.Enrichment analysis indicated that differentially expressed genes were mainly involved in inflammation and immune response and were closely related to osteoclasts.Cross-validation analysis showed that differential gene expression results between the two datasets were consistent.mRNA-miRNA regulatory network analysis revealed that YTHDF2 was negatively correlated with miRNA-27a.Immune infiltration analysis revealed an increase in immune cell infiltration in steroid-induced femoral head necrosis,and YTHDF2 was positively correlated with the infiltration of CD4+T cells.To conclude,m6A-related gene YTHDF2 can serve as a potential biomarker of steroid-induced femoral head necrosis and is valuable for the early clinical diagnosis and treatment of steroid-induced femoral head necrosis.The negative correlation between YTHDF2 and mir-27a and the positive correlation between YTHDF2 and CD4+T cell infiltration provide new insights into the early diagnosis and treatment of steroid-induced femoral head necrosis and shed light on the mechanism of m6A in steroid-induced femoral head necrosis.
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BACKGROUND:The sclerotic zone in the femoral head is an important imaging feature in the progression of steroid-induced femoral head necrosis,which is associated with disease prognosis.Peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α)has been shown to possess biological activities such as osteogenesis,angiogenesis and anti-mitochondrial apoptosis,which may be closely related to bone repair of steroid-induced femoral head necrosis. OBJECTIVE:To screen for the differential proteins in the sclerotic zone of steroid-induced osteonecrosis of the femoral head versus the normal zone,to screen for hub proteins in the sclerotic zone,and to verify the differential expression of hub proteins in the femoral head specimens following steroid-induced femoral head necrosis,and to to explore the repair pattern of the sclerotic zone following steroid-induced femoral head necrosis. METHODS:Femoral head samples were collected from patients with steroid-induced osteonecrosis of the femoral head receiving total hip arthroplasty.The differentially expressed genes in the sclerotic zone and the normal zone were screened by Tandem Mass Tags and analyzed by GO and KEGG signaling pathways to construct a protein-protein interaction network and screen hub genes.In addition,the expression of hub genes in the sclerotic zone was verified by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Quantitative protein profiling by Tandem Mass Tags revealed that 609 proteins were significantly differentially expressed(Log2FC>1.20,Log2FC<0.84 and P<0.05)in the sclerotic zone of the femoral head compared with the normal zone,of which 290 proteins were upregulated and 319 proteins were downregulated.The GO and KEGG pathway enrichment analyses revealed that among the top 10 enriched pathways,Wnt signaling pathway and life-cycle regulatory pathway were closely related to bone repair;in the life-cycle regulatory pathway,PGC-1α was one of the important proteins.In addition,western blot results verified the low expression of PGC-1α and NRF1 in the sclerotic zone and high expression of Cleaved Caspase-3 in the sclerotic zone compared with the normal zone of steroid-induced femoral head necrosis specimens.Light microscopic immunohistochemical results showed the distribution of PGC-1α,NRF1 and Cleaved Caspase-3 positive expression in the sclerotic and normal zones in the femoral head tissue specimens,indicating the presence of their expression in bone trabeculae,osteoblasts and bone marrow.In contrast,the brown area of the sclerotic zone of femoral head necrosis stained darker and showed more obvious expression of Cleaved Caspase-3.To conclude,in the sclerotic zone of steroid-induced femoral head necrosis,biological behaviors including activation of osteogenesis-related pathways such as Wnt and oxidative apoptosis characterized by low expression of PGC-1 are observed.Low expression of PGC-1α in the sclerotic zone of steroid-induced femoral head necrosis may be associated with the activation of oxidative apoptosis.
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BACKGROUND:Currently,there is a lack of large sample studies to analyze the bone metabolism level of patients with femoral head necrosis of different etiologies and stages,which is not conducive to the development of better necrosis-promoting repair strategies. OBJECTIVE:To study the bone metabolism of patients with osteonecrosis of the femoral head with different etiologies and Association Research Circulation Osseous(ARCO)stages. METHODS:A retrospective study was performed on 401 patients diagnosed with osteonecrosis of the femoral head as the trial group,and 81 healthy subjects as the control group.The trial group could be divided into three groups according to different etiologies:steroid-induced osteonecrosis of the femoral head,alcoholic osteonecrosis of the femoral head and traumatic osteonecrosis of the femoral head,and were divided into stages Ⅱ/Ⅲ/Ⅳ according to different ARCO stages.Seven bone metabolism-related indicators of all subjects were collected,including bone metabolism-regulating hormone 25-hydroxyvitamin D and bone conversion markers:N-terminal propeptide of type Ⅰ procollagen,degradation product of type Ⅰ collagen,n-terminal middle molecular fragment of osteocalcin,general biochemical markers of bone metabolism:serum calcium,serum phosphorus,serum alkaline phosphatase.The bone metabolism levels of each group were compared and the independent factors associated with osteonecrosis of the femoral head were determined by binary Logistic regression analysis. RESULTS AND CONCLUSION:Compared with the control group,levels of degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,n-terminal middle molecular fragment of osteocalcin,serum phosphorus and alkaline phosphatase in the trial group were significantly increased(all P<0.05).Based on the presence or absence of the disease,according to binary Logistic regression analysis,degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen,and n-terminal middle molecular fragment of osteocalcin were independent factors associated with osteonecrosis of the femoral head.The levels of degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in three groups of patients with different etiologies were higher than normal reference values.The bone metabolism-regulating hormone 25-hydroxyvitamin D and serum calcium in the alcoholic osteonecrosis of the femoral head group were higher than those in the other two groups(P<0.05).The level of bone metabolism-regulating hormone 25-hydroxyvitamin D in steroid-induced and traumatic osteonecrosis of the femoral head groups was lower than the normal value.There were no significant differences in seven bone metabolism-related indicators in patients with ARCO stages Ⅱ,Ⅲ and Ⅳ osteonecrosis of the femoral head(all P>0.05),but degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen in these three groups were higher than normal reference values.Bone metabolism-regulating hormone 25-hydroxyvitamin D in patients with ARCO stage Ⅱ and ARCO stage Ⅳ was lower than the normal reference value.It is concluded that the bone metabolism level of osteonecrosis of the femoral head patients was abnormal.The degradation product of type Ⅰ collagen and N-terminal propeptide of type Ⅰ procollagen of osteonecrosis of the femoral head patients with different etiologies and ARCO stages were all higher than the normal reference value,and they were in a state of high bone turnover.Degradation product of type Ⅰ collagen,N-terminal propeptide of type Ⅰ procollagen and n-terminal middle molecular fragment of osteocalcin may be risk factors for the pathogenesis of osteonecrosis of the femoral head.
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BACKGROUND:Glucocorticoids can inhibit the expression of hub genes in the parathyroid hormone type Ⅰ receptor(PTH1R)/protein kinase A(PKA)signaling axis and interfere with the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells,leading to the disruption of blood supply in bone and bone tissue structures.Previous studies of the research team showed that Gubitongxiao granules can induce blood vessel formation and inhibit osteoblast apoptosis,which has a certain effect on the prevention and treatment of steroid-induced femoral head necrosis. OBJECTIVE:To observe the therapeutic effect of Gubitongxiao granules in a mouse model of steroid-induced femoral head necrosis,and to explore its mechanism from the PTH1R/PKA signaling axis. METHODS:An animal model of steroid-induced necrosis of the femoral head was established by intraperitoneal injection of lipopolysaccharide and gluteal muscle injection of prednisolone acetate.After identification by nuclear magnetic resonance method,60 mice that were successfully modeled were divided into model group,Gubitongxiao granule group and Tongluo Shenggu capsule group,with 20 mice in each group.Another 12 normal mice were used as control group.The corresponding groups were intragastrically given the corresponding drugs for 12 weeks,and then the samples were taken under anesthesia.Histomorphology of femoral head samples was observed by hematoxylin-eosin staining.Enzyme-linked immunosorbent assay was used to detect the serum levels of bone alkaline phosphatase,type Ⅰ amino-terminal extension peptide,parathyroid hormone,osteocalcin and alkaline phosphatase.Western blot and RT-qPCR were used to detect PTH1R,PKA,myocyte enhancer factor 2,sclerostin and guanylate-binding protein activity-stimulating peptide at protein and gene expression levels,respectively. RESULTS AND CONCLUSION:Gubitongxiao granules may reduce the serum PTH level in mice,inhibit the activation of the PTH1R/PKA signal axis,further up-regulate the protein expressions of sclerostin and myocyte enhancer factor 2,and increase the levels of bone alkaline phosphatase,type Ⅰ amino-terminal extension peptide,osteocalcin and alkaline phosphatase in mice,thus improving femoral head necrosis,which is comparable to the intervention effect of Tongluo Shenggu capsules.It is speculated that Gubitongxiao granules may prevent and treating hormonal femoral head necrosis by regulating the PTH1R/PKA signaling axis.
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BACKGROUND:The distribution of the necrotic area plays an important role in hip preservation treatment.At present,there are few studies on whether the difference in the three-dimensional spatial distribution of osteonecrosis of the femoral head affects the clinical outcome of fibular support. OBJECTIVE:To explore the relationship between the spatial distribution and clinical outcome at the sites of osteonecrosis of the femoral head and fibular support using CT three-dimensional reconstruction so as to provide a basis for optimizing the applicable conditions of fibular support and improving the hip preservation effect of fibular support. METHODS:Eighty patients with osteonecrosis of the femoral head who were treated with fibular support for hip preservation from January 2010 to January 2021 were selected as the study subjects according to the inclusion criteria.They were followed up for at least 2 years.According to the clinical outcome,the patients were divided into the successful hip preservation group(n=55)and the failure hip preservation group(n=25).3D reconstruction was performed according to the preoperative and postoperative CT images of the patients.According to the three-column theory,the femoral head was divided into outer nine areas,middle nine areas and inner nine areas(L1-9,C1-9,and M1-9)to explore the spatial distribution of necrotic area of the femoral head and fibular support area and its relationship with clinical outcome. RESULTS AND CONCLUSION:(1)Before operation,the necrotic area of the femoral head was mainly distributed in L1,L2,L4,L5,C1,C2,C4,and C5(the upper and middle part of the anterior part of the outer ninth area and the middle part of the middle ninth area).After operation,the fibular support area was mainly distributed in L5,L6,C5,and C6(the middle and lower part of the outer ninth area and the middle and lower part of the middle ninth area).(2)There were significant differences in the distribution of osteonecrosis of the femoral head between the successful hip preservation group and the failure hip preservation group in L8(the posterior middle part of the outer ninth area),C3(the anterior lower part of the middle ninth area),C6(the lower middle part of the middle part of the inner ninth area)and M2(the anterior middle part of the inner ninth area)(P<0.05).There was a significant difference in the distribution of fibular support in L5 and L6(middle and lower part of outer nine)(P<0.05).Among them,the L8 region could be used as an independent predictor of hip preservation failure in fibular support surgery.The area under the curve of the L8 single factor prediction model was 0.698[95%CI(0.575,0.822)];the sensitivity was 76%,and the specificity was 63.6%.(3)It turns out,when the necrotic area involves L8,C3,C6,and M2,especially L8,the failure of fibular support may increase,and when the fibular support involves L5 and L6,the effect of hip preservation is often not ideal.
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BACKGROUND:In the selection of minimally invasive total hip arthroplasty approaches,there is considerable debate about whether direct anterior and posterior approaches differ in postoperative gait,limb balance,and hip motor capacity,and therefore further investigation is warranted. OBJECTIVE:To assess the gait and hip ambulation ability of direct anterior and posterior approaches for primary unilateral total hip arthroplasty with a prospective randomized controlled study. METHODS:A total of 61 patients with unilateral avascular necrosis of the femoral head in Qingdao Municipal Hospital from January 2019 to June 2020 were included in the study.There were 40 males and 21 females,at a mean age of(64.83±5.52)years.All the patients were randomly divided into a direct anterior approach group(n=28)and a posterior approach group(n=33),and received initial total hip arthroplasty by direct anterior approach and posterior approach,respectively.Gait analysis(gait time-space parameters such as stride length,stride frequency,single-leg support time,and plantar pressure difference)and hip ambulation ability(standing-walking timing test and 2-minute walking test)were performed before and 1,3 and 6 months after operation. RESULTS AND CONCLUSION:(1)With the extension of postoperative time,gait time-space parameters in both groups were gradually improved.The stride length,stride frequency,single-leg support time,and plantar pressure difference in the direct anterior approach group were significantly better than those in the posterior approach group 1 month after surgery(P<0.01).The stride frequency,single-leg support time,and plantar pressure difference in the direct anterior approach group were significantly better than those in the posterior approach group 3 months after surgery(P<0.05).The plantar pressure difference in the direct anterior approach group was significantly better than that in the posterior approach group 6 months after surgery(P<0.01).(2)With the extension of postoperative time,the results of the standing-walking timing test and 2-minute walking test were gradually improved in both groups.The results of the standing-walking timing test and 2-minute walking test 1 and 3 months after operation in the direct anterior approach group were better than those in the posterior approach group(P<0.05).(3)The results have indicated that the recovery of postoperative gait and hip ambulation ability of the two groups is inconsistent.The direct anterior approach group has some advantages in the improvement of postoperative gait and hip ambulation ability compared with the posterior approach group in the early postoperative period.
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BACKGROUND:Studies have shown that imbalance of bone metabolism during glucocorticoid-induced osteonecrosis of the femoral head necrosis is closely related to oxidative stress. OBJECTIVE:To investigate the pathological mechanism by which oxidative stress-induced ferroptosis promote apoptosis in osteoblasts involved in steroid-induced osteonecrosis of the femoral head. METHODS:General data and serum specimens were collected from 47 patients with steroid-induced osteonecrosis of the femoral head.In addition,six femoral head specimens were collected from these patients.According to the Association Research Circulation Osseous(ARCO)staging system,serum specimens were grouped into ARCO Ⅱ,Ⅲ,and IV,while femoral head specimens were classified into ARCO Ⅲ and IV.Serum levels of malondialdehyde and superoxide dismutase 1 were measured.The protein expression of superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 in the femoral head was detected and verified by Data independent acquisition(DIA)for quantitative sequencing,western blot and alkaline phosphate detection. RESULTS AND CONCLUSION:The ARCO stage of patients with steroid-induced osteonecrosis of the femoral head was independent of age,sex and necrotic side.The serum levels of malondialdehyde and superoxide dismutase 1 were higher in patients with ARCO stage Ⅲ compared with those with ARCO stage Ⅱ and IV.The results of DIA protein quantification showed that the function of differential proteins was mainly related to redox.The levels of superoxide dismutase 1,glutathione peroxidase 4,and Bcl-2 in the necrotic region were lower than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.Western blot verified the results of DIA protein quantification.The alkaline phosphatase activity was lower in the necrotic region than in the normal region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.In the necrotic and sclerotic regions,the function of differential proteins was also related to redox,and superoxide dismutase 1,glutathione peroxidase 4,Bcl-2 protein expression and alkaline phosphatase activity were lower in the necrotic area than in the sclerotic region,as well as lower in ARCO stage IV than in ARCO stage Ⅲ.To conclude,glucocorticoids can influence the progression of steroid-induced osteonecrosis of the femoral head by upregulating oxidative stress levels,inducing osteoblast ferroptosis,and inhibiting osteogenic function.
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BACKGROUND:Free vascularized fibular grafting is an effective hip preservation treatment for femoral head osteonecrosis,but its influencing factors are still controversial. OBJECTIVE:To explore the clinical efficacy of free vascularized fibular grafting for femoral head osteonecrosis,and the influence of the etiology and severity of femoral head osteonecrosis on its efficacy. METHODS:Clinical data and clinical efficacy scores of preoperative and postoperative hip joints in 63 patients with femoral head osteonecrosis(73 cases of hip)were enrolled.The subjects were divided into three groups by the etiological classification criteria of femoral head osteonecrosis,including glucocorticoid-associated,alcohol-associated,and idiopathic groups,and also were divided into three groups by the Ficat classification system,including Ficat Ⅱ,Ficat Ⅲ and Ficat Ⅳ groups.The effects of etiological classification and lesion degree on the clinical efficacy of free vascularized fibular grafting for femoral head osteonecrosis were analyzed. RESULTS AND CONCLUSION:(1)The visual analog scale scores in all periods after free vascularized fibular grafting for femoral head osteonecrosis were significantly decreased compared with preoperative data(P<0.001),and Harris scores were significantly increased compared with preoperative data(P<0.001).(2)In the glucocorticoid-associated,alcohol-associated,and idiopathic groups,except the glucocorticoid-associated group,postoperative Harris scores were significantly increased 2 and 3 years after surgery in other groups compared with preoperative data(P<0.05).(3)In the three groups of Ficat Ⅱ,Ficat Ⅲ,and Ficat Ⅳ,the postoperative Harris scores of Ficat Ⅱ and Ficat Ⅲ groups were significantly increased compared with preoperative data(P<0.05),while the difference was not significant in the Ficat Ⅳ group between the preoperative and postoperative data(P>0.05).(4)These results indicate that the clinical effect of free vascularized fibular grafting for the femoral head osteonecrosis is significant,which can reduce hip pain and improve hip joint function.It may not be affected by the etiology,but by the severity of the femoral head osteonecrosis.