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.

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.

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.

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.

Gene testing for osteonecrosis of the femoral head in systemic lupus erythematosus using targeted next-generation sequencing:A pilot study

BACKGROUND Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head(ONFH)in systemic lupus erythematosus(SLE).Some gene loci such as complement C3d receptor 2(CR2),nitric oxide synthase 3(NOS3),collagen type II alpha 1 chain(COL2A1),protein tyrosine phosphatase non-receptor type 22(PTPN22),and transient receptor potential cation channel subfamily V member 4(TRPV4)were reported to be involved in this process.AIM To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations(SNVs)in these five genes.METHODS SNVs in the CR2,NOS3,COL2A1,PTPN22,and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH.Burrows–wheeler aligner was used to align the sequencing reads to hg19,and GATK and Varscan programs were used to perform SNV calling.PolyPhen-2,SIFT,and MutationTaster were used to assess the functional effects of non-synonymous SNVs.RESULTS Six of the 49 patients were confirmed to have low frequency SNVs,including one patient with SNVs in NOS3(exon 6:c.814G>A:p.E272K and exon 7:c.814G>A:p.E272K.),four in COL2A1(rs41263847:exon 29:c.1913C>T:p.T638I,exon 28:c.1706C>T:p.T569I,and rs371445823:exon 8:c.580G>A:p.A194T,exon 7:c.373G>A:p.A125T),and one in CR2(rs45573035:exon 2:c.200C>G:p.T67S).CONCLUSION The onset of ONFH in SLE might be associated with the identified SNVs in NOS3,COL2A1,and CR2.

Research progress of microRNA in prevention and treatment of osteonecrosis of the femoral head

In the 1980s,Feinbaum et al.first discovered miRNA in the development of worms and termed it as Lin-4.With the development of microbial science and continuous improvement in the gene sequencing technology,miRNA has been gradually gaining attention for intensive research in clinical medicine.Among these,one group of miRNAs has been confirmed to play fundamental roles in gene regulation in various orthopedics diseases,such as bone tumors,osteoarthritis,and rheumatoid arthritis.The study of miRNAs in the osteonecrosis of the femoral head(ONFH)can improve the understanding of the pathogenesis of the disease.ONFH is an orthopedic disease that is the primary cause of disrupted blood supply to the femoral head and the main symptoms of bone and muscle dysfunction.Recent studies showed that miRNA played a major role in the regulation of the microcirculation of ONFH,damage and repair of blood vessels,local microcirculation dysfunction caused by other diseases,and apoptosis of bone cells.In this study,recent related research results of miRNA and ONFH were analyzed and summarized,and the prospective in the prevention and treatment of the disease was also discussed.

Superior Retinacular Artery Did Not Occlude in a Rat Model of the Non-Traumatic Osteonecrosis of the Femoral Head

Non-traumatic osteonecrosis of the femoral head (ONFH) is believed to be avascular necrosis. Certainly, a disruption of a supplying artery induces necrosis in the supplying artery-dominant region. However, when an abnormality such as cell apoptosis, or another reason, is developed in the supplying artery-dominant region, it induces a disruption of the supplying artery. Therefore, to prove that ONFH is avascular necrosis, it is necessary to demonstrate the disruption of the supplying artery prior to histological osteonecrosis development. Here we investigate histologically, using a rat model, whether disruption of the supplying artery occurs before the initial development of ONFH following corticosteroid treatment. Rats were given imiquimod and methylprednisolone, and were sacrificed 1, 2, 3, 7 or 14 days after the last injection. At the sacrifice, the rat was perfused with 20 ml black Indian ink through the left ventricle. ONFH was observed in the Imiquimod + Methylprednisolone group at 7 and 14 days. The osteonecrotic area was not stained with perfused black Indian ink. However, the lateral portion of the femoral head near the superior retinacular artery was stained with the ink. In conclusion, the present study shows that the superior retinacular artery did not occlude before the initial development of ONFH histologically in rats.

Pericollapse Stage of Osteonecrosis of the Femoral Head： A Last Chance for Joint Preservation

Objective： To propose a new definition of the pericollapse stage of osteonecrosis of the femoral head （ONFH） and review its significance in disease diagnosis and treatment selection. Data Sources： A search for eligible studies was conducted in three electronic databases including PubMed, Cochrane Library, and Embase up to August 10, 2018, using the following keywords： ＂osteonecrosis＂, ＂prognosis＂, and ＂treatment＂. Study Selection： Investigations appraising the clinical signs, symptoms, and imaging manifestations in different stages of ONFH were included. Articles evaluating the prognosis of various joint-preserving procedures were also reviewed. Results： The pericollapse stage refers to a continuous period in the development of ONFH from the occurrence of subchondral fracture to early collapse （〈2 mm）, possessing specific imaging features that mainly consist of bone marrow edema and joint effusion on magnetic resonance imaging （MR1）, crescent signs on X-ray films, and clinical manifestations such as the sudden worsening of hip pain. Accumulating evidence has indicated that these findings may be secondary to the changes after subchondral fractures. Of note. computed tomography provides more information for identifying possible subchondral fractures than does MRI and serves as the most sensitive tool for grading the pericollapse lesion stage. The pericollapse stage may indicate a high possibility of progressive disease but also demonstrates satisfactory long- and medium-term outcomes fbr joint-preserving techniques. In tact, if the articular surface subsides more than 2 mm, total hip arthroplasty is preferable. Conclusions： The pericollapse stage with distinct clinical and imaging characteristics provides a last good opportunity for the use of joint-preserving techniques. It is necessary to separate the pericollapse stage as an independent state in evaluating the natural progression of ONFH and selecting an appropriate treatment regimen.

Early Outcomes of Primary Total Hip Arthroplasty for Osteonecrosis of the Femoral Head in Patients with Human Immunodeficiency Virus in China

Background：Studies have reported that patients with human immunodeficiency virus （HIV） have a high incidence of osteonecrosis of the femoral head （ONFH）.Total hip arthroplasty （THA） is an effective management of ONFH.However,little data exist regarding the use of THA for the HIV patients with ONFH in China.This study reviewed the outcomes of HIV-positive patients who underwent THA for ONFH,compared with HIV-negative individuals.Methods：The patients who underwent THA for ONFH from September 2012 to September 2014 in Beijing Ditan Hospital,Capital Medical University were retrospectively studied.Twenty-eight HIV-positive patients and 35 HIV-negative patients underwent 48 THAs and 45 THAs with cementless components,respectively.Medical records and follow-up data were reviewed.Harris Hip Score （HHS） was applied to evaluate the pain and function of the hips before and after THA.Complications such as wound healing,surgical site infection,deep venous thrombosis,pulmonary embolism,sepsis,mortality,and complications from the prosthesis were reviewed.The operation time,blood loss,and hospital stay were compared between the two groups.Results：The mean follow-up period was 19.5 ± 5.8 months （ranging from 6 to 30 months）.The mean age of the HIV-positive patients with osteonecrosis at the time of surgery was 35 years old,which was significantly lower than that of the HIV-negative group （42 years old） （P 〈 0.05）.The HIV-positive patients underwent surgery a mean of 2.5 years after their original symptoms,which was significantly shorter than the HIV-negatives＇ （mean 4 years） （P 〈 0.05）.Among HIV-positive patients,the prevalence of being male and rate of bilateral procedures were significantly higher than those in the HIV-negative group （P 〈 0.05）.The operation time in HIV-positive patients was significantly longer than that in HIV-negative patients （P 〈 0.05）.There were no significant differences in blood loss or hospital stay between the two groups （P 〉 0.05）.The HHSs of two groups significantly improved after THAs （P 〈 0.05）,without significant difference between two groups.No wound complication,sepsis,mortality,prosthesis complication,and occupational exposure occurred,except for two cases of heterotopic ossification and one case of humeral head necrosis.Conclusions：ONFH is more likely to occur bilaterally in younger HIV-positive males.The development of osteonecrosis seems faster in HIV-positive patients than in HIV-negative patients.This should be cautionary for asymptomatic HIV-positive patients with low viral RNA level and in the primary HIV stage.Despite longer operation times in the HIV-positive patients than in the HIV-negative patients,THA is still a safe and efficient approach to treat ONFH in HIV-positive patients.The incidence of complications is much lower than previously reported.However,the long-term follow-up is needed.

Effect of HuoguⅡFormula(活骨Ⅱ方) with Medicinal Guide Radix Achyranthis Bidentatae on Bone Marrow Stem Cells Directional Homing to Necrosis Area after Osteonecrosis of the Femoral Head in Rabbit

Objective： To investigate the effect of Huogu II Formula （活骨 II方 ） with medicinal guide Radix Achyranthis Bidentatae （Ach） on bone marrow stem cells （BMSCs） homing to necrosis area after osteonecrosis of the femoral head （ONFH） frozen by liquid nitrogen in rabbit as well as to explore the mechanism of prevention and treatment for ONFH. Methods： The animal model of ONFH was established by liquid nitrogen frozen on the rabbit left hind leg. Forty-eight Japanese White rabbits were randomly assigned to sham-operated group, model group, Huogu II group, and Huogu II plus Ach group, with 12 rabbits in each. During the course of ONFH animal model establishment, all rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor [rhG-CSF, 30 μg/（kg.day） for continuous 7 days]. Meanwhile, normal saline and decoction of the two formulae were administrated by gavage, respectively. White blood cells （WBC） were counted in peripheral blood before and after injection of rhG-CSF. Materials were drawn on the 2rid and 4th weeks after model built; bone glutamine protein （BGP） and bone morphogenetic protein 2 （BMP2） levels in serum were tested. Histopathologic changes were observed by hematoxylin and eosin （HE） staining. BMP2 mRNA levels were detected with in situ hybridization （iSH） staining. 5-Bromo-2＇-deoxyuridine （BrdU） and stromal cell derived factor 1 （SDF-1） were measured by immunohistochemical assay in femoral head of the left hind leg. Results： Compared with the shamoperated group, the ratio of empty lacuna, serum BGP, and SDF-1 level in the model group increased significantly, and BMP2 in both serum and femoral head decreased significantly. However, in comparison with the model group, the empty lacuna ratio of Huogu II group and Huogu II plus Ach group decreased obviously in addition to the levels of serum BGP and BMP2, and the expressions of BMP2 mRNA, BrdU, and SDF-1 increased significantly. Above changes were particularly obvious in Huogu II plus Ach group. BGP and SDF-1 on the 2nd week and empty lacuna rate and serum BMP2 level on the 4th week in Huogu II group significantly exceeded their counterparts. On the 2nd week, only in Huogu II plus Ach group that the BrdU counting rose significantly. On the 4th week, empty lacuna rate and serum BMP2 level in Huogu II plus Ach group exceeded those in Huogu II group distinctively. Conclusions： To a certain extent, the medicinal guide Ach improves the preventive and therapeutic effects of Huogu II Formula on expedmental ONFH model. The possible mechanism of this is related to its promoting effect on directional homing of BMSCs to the necrosis area.

Effect of superior retinacular artery damage on osteonecrosis of the femoral head

Background Osteonecrosis of the femoral head （ONFH） is the result of dysfunctional blood supply, but associations between specific damaged arteries, imaging changes and clinical sign require more understanding. We investigated characteristics of ONFH that pertain to blood supply, imaging appearance, and clinical feature to judge the prognosis of ONFH.

Modified technique of advanced core decompression for treatment of femoral head osteonecrosis

BACKGROUND Osteonecrosis of the femoral head(ONFH)is a destructive condition most commonly affecting young and middle-aged patients.The leading consequence of ONFH is often a significant articular disability.Effective joint-preserving surgical treatments are urgently needed for patients with early stage ONFH when outcomes of treatment are in general better than the advanced stage disease.AIM To introduce a new surgery procedure called percutaneous expanded core decompression and mixed bone graft technique,which is a new way of jointpreserving surgical treatments.METHODS The clinical data of 6 patients with ONFH diagnosed and treated with the procedure called percutaneous expanded core decompression and mixed bone graft technique at The First Hospital of Qiqihar from March 2013 to August 2019 were retrospectively analyzed;the follow-up ended in December 2019.RESULTS There were 6 male patients with an average age of 43 years in our study.Gratifying results have been obtained from the comparison of Harris hip score,visual analogue scale,and imaging examination before and after operation.CONCLUSION This new modified technique is simple,safe,and reliable.No serious perioperative complications were observed in our cases.Advantages of the single blade expandable reamer are obvious.The adjuvant substance is inexpensive and easy to obtain.Thus,this technique is an effective joint-preserving surgical treatment for patients with early stage of ONFH.

Clinical outcomes of robotic-assisted and manual total hip arthroplasty in the same patient:A case report

BACKGROUND Total hip arthroplasty(THA)is an effective treatment for advanced osteonecrosis of the femoral head,which can significantly relieve pain and improve patients'quality of life.Robotic-assisted THA enhances the accuracy and stability of THA surgery and achieves better clinical outcomes than manual THA.CASE SUMMARY We report the clinical outcomes of robotic-assisted THA and manual THA in the same patient with osteonecrosis of the femoral head.A 49-year-old male patient attended our hospital due to more than 3 years of pain in both hip joints.The left hip was treated with robotic-assisted THA.The patient underwent manual THA of the right hip 3 mo after robotic-assisted THA.We obtained postoperative radiograph parameters,Harris hip score and forgotten joint score of the patient 1 year after surgery.CONCLUSION Compared with manual THA,the patient’s left hip felt better 1 year after roboticassisted THA.Robotic-assisted THA resulted in a better Harris hip score and forgotten joint score than manual THA in the same patient with osteonecrosis of the femoral head.

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 mole 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.

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.

Effect of Gubi Tongxiao granules on osteoblast injury induced by glucocorticoid

Objective:To explore the mechanism of Gubi Tongxiao granule in treating osteoblast injury induced by glucocorticoid.Methods:Mouse osteogenic precursor cell MC3T3-E1 was cultured in vitro,the control group was conventionally cultured,the model group was treated with dexamethasone(10^(-5) M,10^(-6) M,10^(-7) M)solution with gradient concentration to induce injury,and the experimental group was added with Gubi Tongxiao granule drug-containing serum to intervene culture on the basis of the model group.Cell viability was detected by CCK-8 method,autophagy and apoptosis were detected by MDC/PI staining,Beclin-1,Bcl-2 and Bax expression levels were detected by Western-blot,and the expression of target genes in each group was analyzed by RT-qPCR.Results:Compared with the control group,the activity of osteoblasts in the model decreased significantly.The effect of dexamethasone on autophagy and apoptosis of MC3T3-E1 cells was time-dependent and dose-dependent(P<0.05).The autophagy marker Beclin-1 increased at low doses of dexamethasone(10^(-7) or 10^(-6) M)and decreased at high doses(10^(-5) M).Compared with model group,Beclin-1 and Bax mRNA expression in experimental group decreased(P<0.01),and Bcl-2 mRNA expression was significantly up-regulated(P<0.01).In addition,the results of semi-quantitative analysis of apoptosis staining showed that autophagy and apoptosis were inhibited in different degrees(P<0.01).Conclusion:Gubi Tongxiao granule has a protective effect on osteoblast injury caused by dexamethasone,and can effectively reduce autophagy and apoptosis induced by glucocorticoid,which may be one of the mechanisms of maintaining bone mass and delaying the occurrence and development of femoral head necrosis.

Prevalence of Nontraumatic Osteonecrosis of the Femoral Head and its Associated Risk Factors in the Chinese Population： Results from a Nationally Representative Survey

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

Significance of Lateral Pillar in Osteonecrosis of Femoral Head:A Finite Element Analysis

Background： The lateral pillar of the femoral head is an important site for disease development such as osteonecrosis of the femoral head. The femoral head consists of medial, central, and lateral pillars. This study aimed to determine the biomechanical effects of early osteonecrosis in pillars of the femoral head via a finite element （FE） analysis. Methods： A three-dimensional FE model of the intact hip joint was constructed from the image data of a healthy control. Further, a set of six early osteonecrosis models was developed based on the three-pillar classification. The von Mises stress and surface displacements were calculated for all models. Results： The peak values of von Mises stress in the cortical and cancellous bones of normal model were 6.41 MPa and 0.49 MPa, respectively. In models with necrotic lesions in the cortical and cancellous bones, the von Mises stress and displacement of lateral pillar showed significant variability： the stress of cortical bone decreased from 6.41 MPa to 1.51 MPa （76.0% reduction）, while cancellous bone showed an increase from 0.49 MPa to 1.28 MPa （159.0% increase）; surface displacements of cortical and cancellous bones increased from 52.4 μm and 52.1 μm to 67.9 μm （29.5%） and 61.9 μm （18.8%）, respectively. In addition, osteonecrosis affected not only pillars but also adjacent structures in terms of the von Mises stress and surface displacement levels. Conclusions： This study suggested that the early-stage necrosis in the femoral head could increase the risk of collapse, especially in lateral pillar. On the other hand, the cortical part of lateral pillar was found to be the main biomechanical support of femoral head.

The protective effect of icariin on glucocorticoid-damaged BMECs explored by microfluidic organ chip

Osteonecrosis of the femoral head(ONFH)is a devastating musculoskeletal disease characterized by the impaired circulation of bone.The purpose of this study was to explore the underlying mechanisms of the protective effect of icariin on the glucocorticoid-induced injury of bone microvascular endothelial cells(BMECs).Normal BMECs were extracted from the femoral heads by enzymatic isolation and magneticactivated cell sorting methods.Dexamethasone and icariin were used to intervene BMECs in microfluidic organ chips,and phalloidin staining was conducted to observe the cell morphology and viability.Then next-generation transcriptome sequencing and real-time quantitative reverse transcription-polymerase chain reaction(q RT-PCR)were performed to identify the differentially expressed genes(DEGs)in different groups.Through the microfluidic organ chip,it can be observed that after dexamethasone intervention,the filamentous structure in cell fibers disappeared and the cell morphology changed from spindle to round until death.Icariin could relieve these changes and showed a protective effect on glucocorticoiddamaged BMECs.In addition,201 DEGs were detected between the icariin protection group and the dexamethasone group,which were significantly enriched in 17 signaling pathways.8 of the top ten selected hub genes(IL6,PTGS2,VEGFA,etc.)were confirmed by q RT-PCR.Transcription factors(TFs)-gene network showed 63 connections between 18 TFs and 12 DEGs.For instance,GATA2 could regulate 5 DEGs.The associations between 92 mi RNA and 12 DEGs were visualized in a mi RNA-gene network.The hub mi RNA,has-mir-335–5 p was predicted to interact with 8 DEGs(PTGS2,VEGFA,etc.).Microfluidic organ chips could provide excellent morphological results for cell experiments,by which it could be observed that icariin showed a protective effect on the glucocorticoid-induced injury of BMECs.Beside,these DEGs,possible regulatory TF(GATA2,FOXC1,etc.)and mi RNA(has-mir-335–5 p)might be dysregulated in the initiation of ONFH and have prospective importance in ONFH diagnosis and therapy.

Osteogenic potential of human calcitonin gene-related peptide alpha gene-modified bone marrow mesenchymal stem cells

Background Most of the basic and clinical studies of osteonecrosis of the femoral head （ONFH） are restricted to bone tissues only, whereas various systems are involved in the onset and development of ONFH, including nervous system. Peptidergic nerve participates in the neuronal regulation of bone metabolism and anabolism, and plays key roles in the growth, repair and reconstruction of bone. Calcitonin gene-related peptide （CGRP）, which is secreted by peptidergic nerve, is the main mediator of bone metabolism. It dramatically promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells （BMSCs）. Additionally, it enhances the osteoblast mass and the rate of osteoblast formation, and reduces the bone resorption by acting on osteoblasts and osteoclasts. Hence, we aimed to construct recombinant retrovirus vector pLNCX2-hCGRPα and to investigate the proliferation and osteogenic potential of hCGRPα-producing BMSCs （BMSCs/pLNCX2-hCGRPα） after virus infection. Methods The constructed recombinant retrovirus vector pLNCX2-hCGRPα was transfected into PT67 packaging cells by lipofectamine 2000. Virus was collected for BMSCs infection. The mRNA and protein expression of hCGRPα was examined by reverse transcription polymerase chain reaction （RT-PCR） and Western blotting, respectively. The cell proliferation was determined by methyl thiazoleterazolium （MTT） assay. The osteogenic potential of BMSCs was evaluated by alkaline phosphatase （ALP） activity. Results Both mRNA and protein expression of hCGRPα was detected in BMSCs/pLNCX2-hCGRPα cells. These cells exhibited significantly elevated proliferation and ALP value as compared with control BMSCs （P 〈0.05）. Conclusion BMSCs/pLNCX2-hCGRPα cells could stably express hCGRPα and showed promoted proliferation ability and osteogenic potential as compared with control BMSCs.