Previously unexplored etiology for femoral head necrosis:Metagenomics detects no pathogens in necrotic femoral head tissue

BACKGROUND Osteonecrosis of the femoral head(ONFH)is a frequent and refractory disease whose pathogenesis has not yet been elucidated.Infection and other factors that reduce the local blood supply can lead to bone necrosis.AIM To aim of this study was to assess the relationship of ONFH with bone infection by use of metagenomic sequencing.METHODS Twelve patients with idiopathic ONFH and 12 comparable controls who were undergoing hip arthroplasty were followed up in parallel.Necrotic femoral head specimens were collected for bacterial and fungal cultures using standard methods.Bone specimens were subjected to preliminary processing,and metagenomics sequencing of microorganisms was performed.A one-way analysis of variance was used to compare bacterial species in the two groups.RESULTS Bacterial and fungal cultures exhibited no evidence of microbial growth in all isolated necrotic femoral head tissues.We thus performed metagenomic sequencing and classified the species as suspected pathogens or suspected background microorganisms based on known bacterial pathogenicity.There was no evidence of viruses,fungi,parasites,M.tuberculosis complex,or mycoplasma/chlamydia.There were also no significant differences in suspected pathogens or suspected background microorganisms(P>0.05).CONCLUSION Although we found no pathogens specific for ONFH in necrotic femoral head tissue,our research provides a foundation for future research on the metagenomics of bone pathogens.

Surgical Treatment of Osteonecrosis of the Femoral Head Using Minimally Invasive Surgical Drilling and Cancellous Grafting at Brazzaville University Hospital

Introduction: Osteonecrosis of the femoral head (ONTF) is a debilitating condition. Several treatments have been proposed with controversial results. The aim of our study was to evaluate treatment by surgical drilling coupled with in situ cancellous grafting. Materials and methods: Our study was a case-control study conducted at Brazzaville University Hospital from 1st January 2018 to 31 December 2023. It compared two groups of patients with ONTF: non-operated (13 patients, 20 hips) and operated (22 patients, 35 hips). We used the visual digital scale (VDS) for pain assessment, the Merle D’Aubigne-Postel (MDP) scoring system for clinical and functional assessment, and the evolution of necrosis. Results: The group of non-operated patients had a mean age of 35.69 ± 3.4 years, no improvement in pain with an EVN above seven at the last recoil and a mean global MDP score falling from 12.7 before offloading to 10.13 at one year. The group of patients operated on had a mean age of 37.86 ± 7.02 years, a significant reduction in pain (p = 0.00004) and a significantly increased MDP score (p = 0.0034). A comparison of the two groups of patients showed significant stabilization of the necrotic lesions in the operated patients (p = 0.00067), with better satisfaction in the same group. Conclusion: Surgical drilling combined with grafting in the treatment of early-stage ONTF has improved progress in our series. The technique is reproducible and less invasive. It has made it possible to delay unfavorable progression and, consequently, hip replacement surgery.

HISTOMORPHOMETRIC STUDY OF SUBCHONDRAL BONE OF NECROTIC FEMORAL HEAD IN RABBITS INDUCED BY METHYLPREDNISOLONE COMBINED WITH LOW-DOSE LIPOPOLYSACCHARIDE

Objective To investigate the histomorphometric features of the necrotic femoral head of rabbits induced by methylprednisolone combined with lipopolysaccharide. Methods Thirty-two male adult New Zealand white rabbits were used. Among them, 16 were injected with lipopolysaccharide and methylprednisolone (osteonecrosis group), and another 16 were sham-injected with saline (control group). Magnetic resonance (MR) imaging was taken for femoral heads of the rabbits in both groups at the end of 2, 4 and 6 weeks after the injection. All the rabbits were then killed 6 weeks later. The femoral heads of the rabbits were collected and processed for histological and histomorphometric analysis. Results Femoral head necrosis occurred in 14 rabbits of the osteonecrosis group which were confirmed by histological evaluation and MR imaging. Osteonecrotic femoral heads, compared to controls, were characterized by lower values of bone volume/tissue volume (P<0.01), tabecular thichness (P<0.01), osteoid surface/bone surface (P<0.05), mineralizing apposition rate (P<0.05), and bone formation rate/bone surface (P<0.05). However, tabecular separation and eroded surface/bone surface were higher in osteonecrotic femoral heads than in controls (P<0.01). Trabecular number and osteoclast surface/bone surface did not differ significantly. Conclusion The results demonstrated that osteoporosis was apparent in osteonecrotic femoral heads induced by methylprednisolone and lipopolysaccharide, due mainly to trabecular thinning rather than reduction of trabecular number. This might be due to reduced bone formation combined with increased bone resorption.

Effects of individual shock wave therapy vs celecoxib on hip pain caused by femoral head necrosis

BACKGROUND Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head(ONFH),although significant adverse reactions often follow long-term use.Extracorporeal shock wave therapy(ESWT)can delay the progression of ONFH,alleviate the pain and functional limitations it causes,and avoid the adverse effects of celecoxib.AIM To investigate the effects of individual ESWT,a treatment alternative to the use of celecoxib,in alleviating pain and dysfunction caused by ONFH.METHODS This was a randomized,controlled,double-blinded,non-inferiority trial.We examined 80 patients for eligibility in this study;8 patients were excluded based on inclusion and exclusion criteria.A total of 72 subjects with ONFH were randomly assigned to group A(n=36;celecoxib+alendronate+sham-placebo shock wave)or group B(n=36;individual focused shock wave[ESWT based on magnetic resonance imaging three-dimensional(MRI-3D)reconstruction]+alendronate).The outcomes were assessed at baseline,at the end of treatment,and at an 8-wk follow-up.The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score(HHS)(improvement of 10 points or more from the baseline was deemed sufficient).Secondary outcome measures were post-treatment HHS,visual analog scale(VAS),and Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores.RESULTS After treatment,the pain treatment efficiency of group B was greater than that of group A(69%vs 51%;95%CI:4.56%to 40.56%),with non-inferiority thresholds of-4.56%and-10%,respectively.Furthermore,the HHS,WOMAC,and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A(P<0.001).After therapy,the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk(P<0.001),although HHS was only significantly altered at the 2 wk point(P<0.001).On the 1st d and 2nd wk after treatment,HHS and VAS scores were different between groups,with the difference in HHS lasting until week 4.Neither group had severe complications such as skin ulcer infection or lower limb motorsensory disturbance.CONCLUSION Individual shock wave therapy(ESWT)based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.

Effect of Yang-Warming and Kidney-Tonifying Prescription on Expression of Osteogenic and Angiogenic Factors and H-Type Vascular Markers in Steroid-Induced Avascular Necrosis of Femoral Head in Rabbits

Objective: To investigate the effect of Yang-warming and Kidney-tonifying Prescription (YKP) on the treatment of steroid-induced avascular necrosis of the femoral head (SANFH) in rabbits. And to further explore whether its therapeutic mechanism is related to the expression of HIF-1α and VEGF (angiogenic factors), BMP2 and Osterix (osteogenic factor), CD31 (type H vascular marker) and MMP13 (bone destruction-related factor). Methods: Twenty-seven healthy male New Zealand white rabbits were divided into a normal group, model group, traditional Chinese medcine (TCM) group (clinical equivalent dose group of YKP), miR-130a inhibitor group and TCM + inhibitor group. The SANFH model was established by combining horse serum with methylprednisolone. After the model is successfully established, TCM group was given 6.44 g/kg·d YKP by gavage, and the miR-130a gene inhibitor group was intraperitoneally injected with 25 mg/kg miR-130a inhibitor, locked nucleic acid (LNA)-anti-miR-130a. TCM + inhibitor group was treated with YKP intragastrically and miR-130a inhibitor intraperitoneally. The rabbits in the normal group and the model group were intragastrically administered with normal saline 10 ml/d. Once a day for 4 weeks. The avascular necrosis was detected by HE staining. The contents of HIF-1α, VEGF, BMP2 and Osterix in rabbit tissues were detected by qRT-PCR kit, and the expression of CD31 and MMP13 was detected by immunofluorescence staining. Results: In the normal group, the surface of the cartilage layer of the femoral head was smooth, the bone trabeculae were intact and densely arranged, the cells of each layer were neatly arranged, the morphology of the bone cells, the chondrocytes and the adipocytes were normal. In the model group, cartilage surfaces of the femoral head showed exfoliative cracks. The bone trabecular structure was loose and incomplete, chondrocytes, osteoblasts and bone marrow cells were significantly reduced, and the number of empty bone traps was significantly increased. In the TCM-treated group, more chondrocytes, thicker cartilage layer, and more regular bone trabeculae were detected as compared to model rabbits. In contrast, the cartilage layer was thinner, the destruction and fracture of bone trabeculae was more serious, chondrocytes and osteocytes were decreased as compared to model group. The expression of HIF-1α, VEGF, BMP2, and Osterix in the model group decreased significantly as compared to the normal group (P Conclusion: YKP can regulate the expression of angiogenic-related factors (VEGF and HIF-α), osteogenic-related factors (BMP2 and Osterix), and H-type vascular marker CD31, resulting in increased expressions of VEGF, HIF-α, BMP2, and Osterix, which promote intra-femoral head revascularization. Meanwhile, YKP decreased the expression of bone-destruction-related factor MMP13, thus enhancing the ability of bone tissue to repair itself. Regulation of these molecules’ expression may be one of the mechanisms of YKP in the treatment of hormonal femoral head necrosis.

Bone palsy eliminates granules to regulate Wnt/PI3K-AKT signaling pathway and intervene in hormonal osteonecrosis of the femoral head in rabbits

Objective:To investigate the therapeutic effect of osteopathic osteopathy on hormonal osteonecrosis in rabbits by regulating the Wnt/PI3K-AKT signaling pathway.Methods:Thirty clean-grade New Zealand rabbits were randomly divided into control group,model group and experimental group,and all except for the control group,allogeneic serum combined with glucocorticoids were used to establish animal models of simulated hormonal osteonecrosis of the femoral head.After successful modeling,the experimental group was given the model group and the control group the same amount of normal saline,and the experimental group was given bone palsy granule concentrate according to the equivalent dose of humans and rabbits,once a day for 8 weeks,and after intraperitoneal anesthesia,blood was collected from the extracorporeal heart and the serum ALP and TGF-β1 levels were detected by immunoenzyme-linked adsorption.The experimental animals were sacrificed,,and the bilateral femoral heads of rabbits were removed for hematoxylin-eosin staining,and the apoptosis of cells in the femoral head area was observed by TUNEL staining.RT-qPCR analyzed the expression of Bax and Bcl-2 genes,and Western blot detected the expression levels of pathway proteins Wnt,β-catenin,GSK-3β,AKT and p-AKT.Results:Compared with the control group,the expression levels of ALP and TGF-β1 in rabbit bone tissue in the model group decreased significantly(P<0.05),the bone trabeculae were sparse and thinned,the number of hollow bone fosses and the number of apoptosis-positive cells increased significantly(P<0.05),the expression of pro-apoptotic gene Bax was increased,and the expression of anti-apoptotic gene Bcl-2 was inhibited(P<0.05).After the intervention and treatment of bone palsy granules,the hollow bone depression and apoptosis of rabbit bone tissue in the experimental group were effectively improved(P<0.05).In addition,compared with the model group,the osteopathic elimination particles could upregulate the expression of ALP and TGF-β1(P<0.05),promote the expression of pathway proteins Wnt andβ-catenin,increase the phosphorylation level of AKT,and downregulate the expression of GSK-3β(P<0.05).Conclusion:Under glucocorticoids,osteoblast development dysfunction and apoptosis increase.Bone palsy granules can regulate the two signaling pathways of Wnt/PI3K-AKT,promote osteoblast development and inhibit apoptosis,effectively maintain bone metabolic balance,prolong the collapse time of the femoral head,and further treat osteonecrosis of the femoral head.

Regulation of Quan Du Zhong capsule on VEGF/bFGF and expression of Bcl‑2/Bax and Caspase‑3 protein in the repairing process of canine femoral head necrosis

Objective:To explore the repair and treatment effect of Quan Du Zhong capsule on necrosis of femoral head in dogs.Methods:Totally 12 beagles were randomly divided into normal group,model group,Quan Du Zhong capsule group and Xianlinggubao capsule group,with three in each group.In addition to the normal group,the other groups established the femoral head necrosis model by liquid nitrogen alternative freezing.The normal group and the model group did not have any intervention during the modeling period,and the Quan Du Zhong group began to receive the Quan Du Zhong by gavage on the day of modeling;Xianlinggubao capsule group was given Xianlinggubao capsule by gavage once a day for 12 consecutive weeks on the day of modeling.The levels of VEGF and bFGF in the blood vessels of each group at the 12th week were compared,and the ratios of BMD,BS/BV,BV/TV,Tb.Th,Tb.N were measured by Micro CT,and the expressions of Bcl-2,Bax,Caspase-3 proteins were detected by immune reaction.Results:1.Compared with the normal group,the level of serum VEGF and bFGF in the model group decreased after 12 weeks of modeling(P<0.05);Compared with the model group,the levels of serum VEGF and bFGF water in the Xianlinggubao capsule group and the Quan Du Zhong capsule group increased on average at the 12th week of modeling,with statistical difference(P<0.05).The level of the Quan Du Zhong capsule group was the highest,followed by the Xianlinggubao capsule group.2.Compared with the normal group,BMD,BS/BV,BV/TV,Tb.Th and Tb.N in the model group were lower,and Tb.SP were higher,the results were statistically significant(P<0.05).Compared with the model group,the BMD,BV/TV,Tb.Th and Tb.N of Xianlinggubao capsule group and the total eucommia capsule group increased,while the BS/BV and Tb.SP decreased(P<0.05).3.The Quan Du Zhong capsule group and Xianlinggubao capsule group could significantly increase the expression of bcl-2 protein in the femoral head of dogs,which was significantly different from the model group(P<0.05).The expression of bax protein in the femoral head of dogs in the Quan Du Zhong capsule group and the Xianlinggubao capsule group was significantly reduced compared with the model group(P<0.05).The expression of caspase-3 protein in the femoral head of dogs was significantly reduced in the Quan Du Zhong capsule group and Xianlinggubao capsule group,which was significantly different from the model group(P<0.05).Conclusion:Quan Du Zhong capsule can increase the expression of VEGF and bFGF in serum,increase the expression of bcl-2,inhibit the expression of bax,and reduce the expression of caspase-3,which plays a synergistic role in the treatment of avascular necrosis of the femoral head,and has potential targets.

Subchondral fatigue fracture of the femoral head in young military recruits:Potential risk factors

BACKGROUND Subchondral fatigue fracture of the femoral head(SFFFH)mainly occurs in young military recruits and might be confused with osteonecrosis of the femoral head.However,less research focuses on the risk factor for SFFFH.AIM To evaluate the intrinsic risk factors for SFFFH in young military recruits.METHODS X-ray and magnetic resonance imaging data were used for analysis.Acetabular anteversion of the superior acetabulum,acetabular anteversion of the center of the acetabulum(AVcen),anterior acetabular sector angle(AASA),posterior acetabular sector angle,superior acetabular sector angle,neck-shaft angle(NSA),inferior iliac angle(IIA),and ischiopubic angle were calculated.Then,logistic regression,receiver operating characteristic curve analysis,and independent samples t-test were performed to identify the risk factors for SFFFH.RESULTS Based on the results of logistic regression,age[odds ratio(OR):1.33;95%confidence interval(95%CI):1.12-1.65;P=0.0031]and treatment timing(OR:0.86;95%CI:0.75-0.96;P=0.015)could be considered as the indicators for SFFFH.AVcen(P=0.0334),AASA(P=0.0002),NSA(P=0.0007),and IIA(P=0.0316)were considered to have statistical significance.Further,AVcen(OR:1.41;95%CI:1.04-1.95)and AASA(OR:1.44;95%CI:1.21-1.77),especially AASA(area under curve:66.6%),should be paid much more attention due to the higher OR than other indicators.CONCLUSION We have for the first time unveiled that AASA and age could be key risk factors for SFFFH,which further verifies that deficient anterior coverage of the acetabulum might be the main cause of SFFFH.

Efficacy and risk factors for anxiety and depression after miniincision hip arthroplasty for femoral head osteonecrosis

BACKGROUND Osteonecrosis of the femoral head(ONFH)is a prevalent orthopedic issue,leading to the collapse and fragmentation of the femoral head in its advanced stages,which can severely impair patients'quality of life.Total hip arthroplasty(THA)is a clinical intervention frequently used to alleviate ONFH symptoms and reinstate hip functionality.The conventional surgical technique is invasive and comes with an extended recuperation period,posing significant challenges for patients.With the progression of medical technology,the use of the mini-incision technique in minimally invasive THA(MITHA)has become more prevalent.However,comparative studies examining the effectiveness of these two surgical procedures in treating ONFH remain scarce.Furthermore,understanding patients'psychological well-being is crucial given its profound influence on postoperative recuperation.AIM To evaluate the impact of mini-incision MITHA on ONFH treatment and to identify the risk factors associated with postoperative anxiety and depression.METHODS A retrospective study was conducted on 125 patients treated for ONFH at Xi’an Hong Hui Hospital between February 2020 and January 2022,with the term"consecutive"indicating that these patients were treated in an unbroken sequence without any selection.Among these,60 patients(control group)underwent traditional THA,while 65 patients(observation group)were treated with miniincision MITHA.Variations in the visual analog scale(VAS)score and the Harris hip score were monitored.Additionally,shifts in pre-and posttreatment Hamilton anxiety(HAMA)and Hamilton depression(HAMD)scale scores were recorded.Patients with both postoperative HAMA and HAMD scores of≥8 were identified as those experiencing negative emotions.Logistic regression was utilized to analyze the determinants influencing these negative emotional outcomes.Comparative analyses of surgical and postoperative metrics between the two groups were also conducted.RESULTS Posttreatment results indicated a significantly higher VAS score in the control group than in the observation group,while the Harris score was considerably lower(P<0.0001).The observation group benefited from a notably shorter operation duration,reduced blood loss,diminished incision size,and a decreased postoperative drainage time(P<0.0001),accompanied by a reduced hospital stay and lower treatment costs(P<0.0001).The control group had elevated posttreatment HAMA and HAMD scores in comparison to the observation group(P<0.0001).Multivariate logistic regression revealed that being female[odds ratio(OR):4.394,95%CI:1.689-11.433,P=0.002],having a higher postoperative VAS score(OR:5.533,95%CI:2.210-13.848,P<0.0001),and having higher treatment costs(OR:7.306,95%CI:2.801-19.057,P<0.0001)were significant independent determinants influencing postoperative mood disturbances.CONCLUSION Compared to conventional THA,mini-incision MITHA offers advantages such as reduced operation time,minimal bleeding,and a shorter incision in ONFH patients.Moreover,factors such as sex,postoperative pain(reflected in the VAS score),and treatment costs significantly impact postoperative anxiety and depression.

The role and research progress of PI3K/AKT signaling pathway in non-traumatic osteonecrosis of the femoral head

Non-traumatic osteonecrosis of the femoral head(NONFH)is one of the most common orthopedic diseases,influenced by multiple signaling pathways and inflammatory factors.The PI3K/AKT signaling pathway is closely related to various biological processes such as apoptosis,autophagy,and metabolism in cells.Increasing evidence suggests that it plays an important role in the development of femoral head necrosis.This paper aims to explore the mechanism of the PI3K/AKT signaling pathway in the pathogenesis of NONFH by analyzing its regulation of lipid metabolism,cell apoptosis and autophagy,and intravascular coagulation.This study provides new insights for the research of NONFH.

Current Status of Research on Treatment of Osteonecrosis of Femoral Head with Traditional Chinese Medicine from the Perspective of Security-based Chinese Medicine

The publication of"Evidence-based Chinese Medicine"and the establishment of the Chinese Traditional Medicine Evidence-based Medicine Center mark that evidentiary-based Chinese medicine has stood in front of all Chinese medicine practices in the form of new disciplines,greatly promoting the modernization of Chinese medicine.It will always give Chinese medicine a powerful impetus to the world.Femoral head necrosis is the dominant disease in the treatment of TCM.Chinese medicine practices should seize the optionality to active learn the content of evidentiary-based Chinese medicine and apply it to clinical and scientific research practice.This article review the development status of femoral head necrosis treatment by TCM medicine from the perspective of event-based Chinese medicine.It provides a reference for the event-based development of Chinese medicine in the treatment of femoral head necrosis,and continues to develop advantages and make up for the shortcomings.

Reconstructing avascular necrotic femoral head through a bioactiveβ-TCP system:From design to application

A variety of techniques have been used for treating avascular necrosis of the femoral head(ANFH),but have frequently failed.In this study,we proposed aβ-TCP system for the treatment of ANFH by boosting revascularization and bone regeneration.The angio-conductive properties and concurrent osteogenesis of the highly interconnected porousβ-TCP scaffold were revealed and quantified through an in vivo model that simulated the ischemic environment of ANFH.Mechanical test and finite element analysis showed that the mechanical loss caused by tissue necrosis and surgery was immediately partially compensated after implantation,and the strength of the operated femoral head was adaptively increased and eventually returned to normal bone,along with continuous material degradation and bone regeneration.For translational application,we further conducted a multi-center open-label clinical trial to assess the efficacy of theβ-TCP system in treating ANFH.Two hundred fourteen patients with 246 hips were enrolled for evaluation,and 82.1%of the operated hips survived at a 42.79-month median follow-up.The imaging results,hip function,and pain scores were dramatically improved compared to preoperative levels.ARCO stage II disease outperformed stage III in terms of clinical effectiveness.Thus,bio-adaptive reconstruction using theβ-TCP system is a promising hip-preserving strategy for the treatment of ANFH.

A Rabbit Model of Hormone-induced Early Avascular Necrosis of the Femoral Head

Objective To establish an experimental model of early stage avascular necrosis of the femoral head （ANFH） caused by corticosteroid in adult rabbits and to observe the pathological changes with various imaging techniques. Methods ANFH was induced by a combination of hypersensitivity vasculitis caused by injection of horse serum and subsequent administration of a high dose of corticosteroid. The pathological changes were detected with digital radiography （DR）, computed tomography （CT）, magnetic resonance imaging （MRI）, ink artery infusion angiography, hematoxylin-eosin staining, and immunohistochemistry. Results The imageological and pathological changes corresponded to the clinical characteristics of early stage ANFH. DR showed bilaterally increased bone density, an unclear epiphyseal line, and blurred texture of cancellous bone. CT showed spot-like low-density imaging of cancellous bone, thinner cortical bone, osteoporosis, and an unclear epiphyseal line. MR! showed bone marrow edema and spot-like high signals in T2-weighted imaging in cancellous bone. Ink artery infusion angiography showed fewer obstructed blood vessels in the femoral head. HE staining of pathological sections showed fewer trabeculae and thin bone, an increased proportion of empty osteocyte lacunae, decreased hematopoiesis, thrombosis, and fat cell hypertrophy. Immunohistochemistry showed attenuated expression of vascular endothelial growth factor in osteoblasts and chondrocytes, and on the inner membrane of blood vessels. Conclusion Experimental rabbit model of early stage ANFH caused by corticosteroid can be successfully established and provide the foundation for developing effective methods to treat early stage ANFH.

Association of Toll-like receptor 4 Signaling Pathway with Steroid-induced Femoral Head Osteonecrosis in Rats

Osteonecrosis of the femoral head is frequently observed in patients treated with excessive corticosteroids. However, the pathogenesis of corticosteroid-induced osteonecrosis remains unclear. The purpose of this study was to investigate the role of Toil-like receptor 4 （TLR4） signaling pathway in steroid-induced femoral head osteonecrosis in rats. Male Sprague-Dawley rats were injected intramus- cularly with 20 mg/kg methylprednisolone （MP） for 8 weeks, twice per week. The animals were sacri- ficed at 2, 4 and 8 weeks after the last MP injection, respectively, and then allocated to the 2-, 4- and 8-week model groups （n=24 each）. Rats in the control group （n=12） were not given any treatment. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase （TRAP） in plasma was determined. The activation of osteoclasts in the femoral head was assessed by TRAP staining. The expression of TLR4, MyD88, TRAF6 and NF-Id3 p65 that are involved in TLR4 signaling, and MCP-1 production were detected by using real-time PCR （RT-PCR） and Western blotting. The results showed that the osteonecrosis in the femoral head was clearly observed and the concentra- tion of TRAP in the plasma was increased in the model rats. The femoral head tissues in MP-treated rats were positive for TRAP and the intensity of TRAP staining was greater in MP-treated rats than in con- trol rats. As compared with the control group, the mRNA expression of TLR4 signaling-related factors was enhanced significantly at 4 and 8 weeks, and the protein levels of these factors increased signifi- cantly with time. It was concluded that MP could induce the femoral head osteonecrosis in rats, which was associated with osteoclast activation via the TLR4 signaling pathway. These findings suggest that TLR4 signaling pathway plays a pivotal role in the pathogenesis of steroid-induced osteonecrosis.

Experimental Study of Vascular Endothelial Growth Factor Gene Therapy for Avascular Necrosis of the Femoral Head

To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression of vascular endothelial growth factor (VEGF) was detected by RNA dot hybridization and immunohistochemical method The repair of the femoral head was observed by histological method The results showed that the expression of VEGF was detectable in the femoral head treated with VEGF gene Angiogenesis in these femoral heads was more abundant than the control Bone repairing was augmented in the femoral head treated with VEGF gene The results suggest that angiogenesis in bone tissue could be augmented by gene transfection of VEGF and bone repairing would be accelerated accordingly

Microstructures and properties of cancellous bone of avascular necrosis of femoral heads

The aim of this study is to investigate microscopic structure and characterize cancellous bone of avascular necrosis of the femoral head （ANFH）. The rabbit model of the ANFH is established. The histopathologic features are studied successfully. The differences between the steroidinjection group （S.G.） and the controlled group （C.G.） are examined, including the weight of rabbits, the hematological examination and the three-dimensional stnactures. It is found that the plasma levels of cholesterol （CHO）, high-density lipoprotein （HDL） and low-density lipoprotein （LDL） in S.G. are lower than those in C.G. when the triglyceride （TG） increased in the S.G.; but the bone mineral content （BMC） and the structural model index （SMI） of the organ and tissue decreased significantly in S.G. Three-dimensional structures of the femoral head are obtained using micro-computed tomography （CT） scanning and the mechanical model is established to analyze the influences of these structural changes on the mechanical properties of the cancellous bone.

Safety and efficacy of surgical hip dislocation in managing femoral head fractures: A systematic review and meta-analysis

BACKGROUND Femoral head fractures(FHFs)are considered relatively uncommon injuries;however,open reduction and internal fixation is preferred for most displaced fractures.Several surgical approaches had been utilized with controversial results;surgical hip dislocation(SHD)is among these approaches,with the reputation of being demanding and leading to higher complication rates.AIM To determine the efficacy and safety of SHD in managing FHFs by reviewing the results reported in the literature.METHODS Major databases including PubMed,Embase,Web of Science,and Cochrane Central Register of Controlled Trials were searched to identify studies reporting on outcomes of SHD utilized as an approach in treating FHFs.We extracted basic studies data,surgery-related data,functional outcomes,radiological outcomes,and postoperative complications.We calculated the mean differences for continuous data with 95%confidence intervals for each outcome and the odds ratio with 95%confidence intervals for binary outcomes.P<0.05 was considered significant.RESULTS Our search retrieved nine studies meeting our inclusion criteria,with a total of 129 FHFs.The results of our analysis revealed that the average operation time was 123.74 min,while the average blood loss was 491.89 mL.After an average followup of 38.4 mo,a satisfactory clinical outcome was achieved in 85%of patients,ranged from 30%to 86%,with avascular necrosis,heterotopic ossification,and osteoarthritis being the most common complications occurring at an incidence of 12%,25%,and 16%,respectively.Trochanteric flip osteotomy nonunion and trochanteric bursitis as a unique complication of SHD occurred at an incidence of 3.4%and 3.8%,respectively.CONCLUSION The integration of SHD approach for dealing with FHFs offered acceptable functional and radiological outcomes with a wide range of safety in regards to the hip joint vascularity and the development of avascular necrosis,the formation of heterotopic ossification,and the development of posttraumatic osteoarthritis;however,it still carries its unique risk of trochanteric flip osteotomy nonunion and persistent lateral thigh pain.

Tissue level microstructure and mechanical properties of the femoral head in the proximal femur of fracture patients

This study aims to investigate the regional variations of trabecular morphological parameters and mechanical parameters of the femoral head,as well as to determine the relationship between trabecular morphological and mechanical parameters.Seven femoral heads from patients with fractured proximal femur were scanned using a micro-CT system.Each femoral head was divided into 12 sub-regions according to the trabecular orientation.One 125 mm^3 trabecular cubic model was reconstructed from each sub-region.A total of 81 trabecular models were reconstructed,except three destroyed sub-regions from two femoral heads during the surgery.Trabecular morphological parameters,i.e.trabecular separation（Tb.Sp）,trabecular thickness（Tb.Th）,specific bone surface（BS/B V）,bone volume fraction（BV/TV）,structural model index（SMI）,and degree of anisotropy（DA） were measured.Micro-finite element analyses were performed for each cube to obtain the apparent Young＇s modulus and tissue level von Mises stress distribution under 1%compressive strain along three orthogonal directions,respectively.Results revealed significant regional variations in the morphological parameters（P〈0.05）.Young＇s moduli along the trabecular orientation were significantly higher than those along the other two directions.In general,trabecular mechanical properties in the medial region were lower than those in the lateral region.Trabecular mechanical parameters along the trabecular orientation were significantly correlated with BS/BV,BV/TV,Tb.Th,and DA.In this study,regional variations of microstructural features and mechanical properties in the femoral head of patients with proximal femur fracture were thoroughly investigated at the tissue level.The results of this study will help to elucidate the mechanism of femoral head fracture for reducing fracture risk and developing treatment strategies for the elderly.

Protective Effect of Human Umbilical Cord Mesenchymal Stem Cells in Glucocorticoid-induced Osteonecrosis of Femoral Head

Objective:To evaluate the effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on preventing rats from glucocorticoid-induced osteonecrosis of femoral head(GC-ONFH)in the early stage in vivo and to investigate the possible mechanism of hUC-MSCs in regulating the balance of osteogenesis and adipogenesis.Methods:All rats were randomly divided into 3 groups:control group(C group),model group(M group),and intervention group(Ⅰ group).The model of GC-ONFH was developed by a sequential administration of lipopolysaccharide and methylprednisolone.The rats in the Ⅰ group were treated with caudal vein injection of hUC-MSCs.Six weeks later,the blood samples were obtained to measure the activity of alkaline phosphatase(ALP)and the content of triglyceride(TG)in serum,and the femoral heads were harvested and observed by hematoxylin-eosin staining,Micro-CT,Western blot and real-time quantitative polymerase chain reaction.Results:After intervention of hUC-MSCs,the necrosis rate of femoral head decreased from 83%(10/12)to 33%(4/12),the rate of empty bone lacuna was significantly decreased,the activity of ALP increased significantly,the content of TG decreased significantly,the bone density increased obviously,the expression of RUNX2 and Col Ⅰ increased significantly and the expression of PPARγ decreased significantly.Conclusion:These results revealed that caudal vein injection of hUC-MSCs can effectively reduce the incidence of GC-ONFH in rats by increasing ALP activity and reducing TG content in serum,increasing bone mineral density,promoting the expression of RUNX2 and Col I,and inhibiting the expression of PPARγ.

Surface-based map plasticity of brain regions related to sensory motor and pain information processing after osteonecrosis of the femoral head

Pain is one of the manifestations of hip disorder and has been proven to lead to the remodeling of somatotopic map plasticity in the cortex.However,most studies are volume-based which may lead to inaccurate anatomical positioning of functional data.The methods that work on the cortical surface may be more sensitive than those using the full brain volume and thus be more suitable for map plasticity study.In this prospective cross-sectional study performed in Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,20 patients with osteonecrosis of the femoral head(12 males and 8 females,aged 56.80±13.60 years)and 20 healthy controls(9 males and 11 females,aged 54.56±10.23 years)were included in this study.Data of resting-state functional magnetic resonance imaging were collected.The results revealed that compared with healthy controls,compared with the healthy controls,patients with osteonecrosis of the femoral head(ONFH)showed significantly increased surface-based regional homogeneity(Re Ho)in areas distributed mainly in the left dorsolateral prefrontal cortex,frontal eye field,right frontal eye field,and the premotor cortex and decreased surface-based Re Ho in the right primary motor cortex and primary sensory cortex.Regions showing significant differences in surfacebased Re Ho values between the healthy controls and patients with ONFH were defined as the regions of interests.Seed-based functional connectivity was performed to investigate interregional functional synchronization.When the areas with decreased surface-based Re Ho in the frontal eye field and right premotor cortex were used as the regions of interest,compared with the healthy controls,the patients with ONFH displayed increased functional connectivity in the right middle frontal cortex and right inferior parietal cortex and decreased functional connectivity in the right precentral cortex and right middle occipital cortex.Compared with healthy controls,patients with ONFH showed significantly decreased cortical thickness in the para-insular area,posterior insular area,anterior superior temporal area,frontal eye field and supplementary motor cortex and reduced volume of subcortical gray matter nuclei in the right nucleus accumbens.These findings suggest that hip disorder patients showed cortical plasticity changes,mainly in sensorimotor-and pain-related regions.This study was approved by the Medical Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine(approval No.2018-041)on August 1,2018.