Bilateral Avascular Necrosis of the Femoral Head in Renal Transplant Recipient: A Case Report

Osteoarticular complications are common after renal transplantation. The complications may result from the bone condition prior to transplantation or the iatrogenic effects of the treatments administered. These complications lead to significant morbidity and mortality, in addition to chronic pain and functional impairment. We report the clinical case of bilateral avascular necrosis (AVN) of the femoral head in a kidney transplant recipient. Clinical Case: 53-year-old male with a history of chronic hypertension. He underwent chronic hemodialysis for 12 months and was treated with Entecavir for chronic hepatitis B. The patient received a kidney transplant from a non-related living donor. Induction therapy included Thymoglobulin along with tapered corticosteroids, reaching a dose of 5 mg/day after 3 months, Mycophenolate mofetil (2 g/day), and Tacrolimus adjusted based on residual levels. There was good recovery of renal graft function. After six months, the patient reported bilateral hip pain and functional impairment of both lower limbs. Pelvic X-rays showed signs suggestive of bilateral AVN of the femoral heads. The diagnosis was confirmed by MRI. The patient underwent right hip drilling and total left hip replacement (THR). A right THR was performed a year later. Conclusion: AVN constitutes a frequent cause of morbidity and mortality after RT. The pathophysiology of osteonecrosis remains complex and multifactorial. We emphasize the importance of conducting a thorough assessment of bone health in patients both before and after RT.

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.

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.

Current concepts on osteonecrosis of the femoral head

It is estimated that 20000 to 30000 new patients are diagnosed with osteonecrosis annually accounting for approximately 10% of the 250000 total hip arthroplasties done annually in the United States. Thelack of level 1 evidence in the literature makes it difficult to identify optimal treatment protocols to manage patients with pre-collapse avascular necrosis of the femoral head, and early intervention prior to collapse is critical to successful outcomes in joint preserving procedures. There have been a variety of traumatic and atraumatic factors that have been identified as risk factors for osteonecrosis, but the etiology and pathogenesis still remains unclear. Current osteonecrosis diagnosis is dependent upon plain anteroposterior and frog-leg lateral radiographs of the hip, followed by magnetic resonance imaging(MRI). Generally, the first radiographic changes seen by radiograph will be cystic and sclerotic changes in the femoral head. Although the diagnosis may be made by radiograph, plain radiographs are generally insufficient for early diagnosis, therefore MRI is considered the most accurate benchmark. Treatment options include pharmacologic agents such as bisphosphonates and statins, biophysical treatments, as well as joint-preserving and joint-replacing surgeries. the surgical treatment of osteonecrosis of the femoral head can be divided into two major branches: femoral head sparing procedures(FHSP) and femoral head replacement procedures(FHRP). In general, FHSP are indicated at pre-collapse stages with minimal symptoms whereas FHRP are preferred at post-collapse symptomatic stages. It is difficult to know whether any treatment modality changes the natural history of core decompression since the true natural history of core decompression has not been delineated.

Osteonecrosis of the femoral head: An update in year 2012

Osteonecrosis is a phenomenon involving disruption to the vascular supply to the femoral head, resulting in articular surface collapse and eventual osteoarthritis. Although alcoholism, steroid use, and hip trauma remain the most common causes, several other etiologies for osteonecrosis have been identified. Basic science research utilizing animal models and stem cell applications continue to further elucidate the pathophysiology of osteonecrosis and promise novel treatment options in the future. Clinical studies evaluating modern joint-sparing procedures have demonstrated significant improvements in outcomes, but hip arthroplasty is still the most common procedure performed in these affected younger adults. Further advances in joint-preserving procedures are required and will be widely studied in the coming decade.

Modified porous tantalum rod technique for the treatment of femoral head osteonecrosis

AIM: To study a modified porous tantalum technique for the treatment of osteonecrosis of the femoral head.METHODS: The porous tantalum rod was combined with endoscopy,curettage,autologous bone grafting and use of bone marrow aspirates from iliac crest aspiration in 49 patients(58 hips) with a mean age of 38 years.The majority of the patients had idiopathic osteonecrosis,followed by corticosteroid-induced osteonecrosis.Thirtyeight hips were of Steinberg stage Ⅱ disease and 20 hips were of stage Ⅲ disease.Patients were followed for 5 years and were evaluated clinically with the Merle D'Aubigne and Postel score and radiologically.The primary outcome of the study was survival based on the conversion to total hip arthroplasty(THA).Secondary outcomes included deterioration of the osteonecrosis to a higher disease stage at 5 years compared to the preoperative period and identification of factors that were associated with survival.The Kaplan-Meier survival analysis was performed to evaluate the survivorship ofthe prosthesis,and the Fisher exact test was performed to test associations between various parameters with survival.RESULTS: No patient developed any serious intraoperative or postoperative complication including implant loosening or migration and donor site morbidity.During the 5-year follow up,1 patient died,7 patients had disease progression and 4 hips were converted to THA.The 5-year survival based on conversion to THA was 93.1% and the respective rate based on disease progression was 87.9%.Stage Ⅱ disease was associated with statistically significant better survival rates compared to stage Ⅲ disease(P = 0.04).The comparison between idiopathic and non-idiopathic osteonecrosis and between steroid-induced and non-steroid-induced osteonecrosis did not showed any statistically significant difference in survival rates.The clinical evaluation revealed statistically significantly improved Merle d'Aubigne scores at 12 mo postoperatively compared to the preoperative period(P < 0.001).The mean preoperative Merle d'Aubigne score was 13.0(SD: 1.8).The respective score at 12 mo improved to 17.0(SD: 2.0).The 12-mo mean score was retained at 5 years.CONCLUSION: The modified porous tantalum rod technique presented here showed encouraging outcomes.The survival rates based on conversion to THA are the lowest reported in the published literature.

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.

Effect of recombinant human bone morphogenetic protein 2/polylactide-co-glycolic acid (rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis

Objective:To observe the effect of recombinant human bone morphogenetic protein 2/polylactide-co-glycolic acid(rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis.Methods:Bilateral femoral head necrosis models of rabbit were established by steroid injection.A total of 48 rabbits(96 femoral head necrosis) were randomly divided into 4groups:Group A,control group with12 rabbits,24 femoral head necrosis;Group B,treated with rhBMP-2/PLCA implantation after core depression,with 12 rabbits,24 femoral head necrosis;Group C,treated with rhBMP-2 implantation after core depression,with 12 rabbits,24 femoral head necrosis;Croup D treated with core depression group without implantation,with 12 rabbits,24 femoral head necrosis.All animals were sacrificed after 12 weeks.The ability of repairing bone defect was evaluated by X-ray radiograph.Bone mineral density analysis of the defect regions were used to evaluate the level of ossification.The morphologic change and bone formation was assessed by HE staining.The angiogenesis was evaluated by VEGF immunohistochemistry.Results:The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation.And the angiogenesis in group B was better than other groups.Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D.Conclusions:The treatment of rhBMP-2/PLCA implantation after core depression can promote the repair of rabbit femoral head necrosis.It is a promising and efficient synthetic bone material to treat the femoral head necrosis.

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.

Vascular endothelial growth factor for the treatment of femoral head osteonecrosis: An experimental study in canines

AIM To evaluate the treatment of osteonecrosis of the femoral head(ONFH) with the use of vascular endothelial growth factor(VEGF).METHODS In 30 mature beagles(6 groups of 5 beagles) ONFH was induced cryosurgically and one of the following solutions was administered locally in the femoral head(FH) in each group: Single injection of 500 μg VEGF(t-VEGFμ group); single injection of 500 ng VEGF(t-VEGFn group); continuous delivery of 500 μg VEGF through osmotic micropump(t-VEGFpump-μ group); continuous delivery of 500 ng VEGF through osmotic micropump(t-VEGFpump-n group); single injection of 0.9% sodium chloride(t-NS group), while one group that served as control group did not receive any local solution(No-t group). FHs were retrieved 12 wk postoperatively, underwent decalcification and hematoxylin/eosin and toluidine blue staining. In two canines per group, one half of FH was processed without decalcification and stained with modified Masson Trichrome. Histological sections were observed by light microscopy and measured with a semi-automatized bone histomorphometry system and Bone Volume/Total Volume(BV/TV), Marrow Volume/Total Volume(MaV/TV), and Trabecular Thickness(TbT h) were assessed. Standard and robust tests(Welch, Brown Forsythe) of analysis of variance along with multiple comparisons, were carried out among the categories.RESULTS The untreated(No-t) group had signs of osteonecrosis, whereas the VEGF groups revealed reversal of the osteonecrosis. Statistical analysis of the decalcified specimens revealed a significantly better BV/TV ratio and a higher Tb Th between the VEGF treatment groups(except the t-VEGFn group) and the No-t group or the control t-NS group. Single dose 500 μg VEGF group had significantly better BV/TV ratio and higher Tb Th when compared to the No-t group(50.45 ± 6.18 vs 29.50 ± 12.27, P = 0.002 and 151.44 ± 19.07 vs 107.77 ± 35.15, P = 0.161 respectively) and the control t-NS group(50.45 ± 6.18 vs 30.9 ± 6.67, P = 0.004 and 151.44 ± 19.07 vs 107.14 ± 35.71, P = 0.151 respectively). Similar differences were found for the prolonged VEGF delivery/pump groups of 500 μg and 500 ng. Analysis of the totality of specimens(decalcified/non-decalcified) enhanced the aforementioned differences and additionally revealed significant differences in the comparison of the TbT h.CONCLUSION In an experimental model of ONFH in canines it was found that local treatment with VEGF leads to bone tissue remodeling and new bone formation.

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.

Effect of <i>Qing’e Pill</i>plus <i>Salvia</i>on Non-Traumatic Osteonecrosis of the Femoral Head of Idiopathic Type in Earlier Stage: A Case Report of a Twelve-Month of Period

Background: Compromised circulatory and bone/lipid metabolic dysfunction are two major contributors to non-traumatic osteonecrosis of the femoral head (ONFH). Qing’e pill plus Salvia has significant anti-inflammatory and anti-atherosclerotic action, and it could also regulate bone formation and remodeling by suppressing osteoclasts. Case Report: We describe a case of a 62-year- old man with ONFH of idiopathic type in earlier stage that could not be adequately controlled with oral non-steroidal analgesics and restoring bone loss agents for past 3 years. After six months treatment with Qing’e pill plus Salvia, the plasma low-density lipoprotein (LDL), high-density lipoprotein (HDL), apolipoprotein A1 (apo A1), apolipoprotein B (apo B), total cholesterol (TC), triglycerides (TG), and blood viscosity were measured on an empty stomach. The Harris scores were maintained during a six months follow-up after discontinuation of Qing’e pill plus Salvia. Discussion: Our case has shown that plasma levels of inflammatory and atherosclerotic relaxed factors and the Harris scores may be controlled with herbal medication in ONFH of idiopathic type in earlier stage that could not be adequately controlled with oral non-steroidal analgesics and restoring bone loss agents.