Summary Statement. Osteonecrosis of the femoral head (ONFH) is a multifactorial skeletal disorder. S100A9 represseses angiogenesis and vessel integrity in ONFH. It also may function as a marker of diagnosis in ONFH. Introduction. Osteonecrosis of the femoral head (ONFH) is a multifactorial skeletal disorder characterised by ischemic deterioration, bone marrow edema and eventually femoral head collapse and joint destruction. Several surgical, pharmaceutical and non-invasive biophysical modalities have been employed to alleviate this joint disorder. Our proteomic analysis showed that ONFH patients displayed increased expression of S100A9 protein when compared with healthy volunteers. This study is designed to evaluate the pathogenesis of S100A9 on the patients of ONFH. Patients & Methods. We collected 56 patients with ONFH including stage I, II, III and IV and 14 health volunteers. 20 ml of peripheral venous blood is drawn from each subject or prior to general anesthesia for hip arthroplasty. We compared the ELISA of S100A9, Osteocalcin, TRAP-5b, sVCAM-1. Immunohistochemistry of S100A9, vWF and VEGF are compared using femoral head harvested from late stages of ONFH and femoral neck fracture when received hip arthroplasty. In vitro angiogenic assay was performed by tube formation assay. Results. There were significant elevation of S100A9 in the serum of ONFH patients then in healthy volunteers. sVCAM-1 and TRAP-5b were increased and Osteocalcin was decreased in ONFH patient when comapred with healthy volunteers. The expression of S100A9 protein in ONFH tissue was significantly higher than femoral neck fracture tissue. In tube formation assay, we found S100A9 and the serum of ONFH patient supressed angiogenesis in vascular endothelial cell culture. Discussion/Conclusion. The expression of S100A9 significantly increased in the serum and femoral head tissue of patients with ONFH. S100A9 also supressed angiogenesis expression. The results indicated that S100A9 represseses angiogenesis and vessel integrity in ONFH. It also may function as a marker of diagnosis in ONFH

Introduction

Collapse of femoral head associated with end-stage arthritis form hallmark of osteonecrosis of femoral head. Purpose was to assess efficacy of platelet rich plasma following core decompression in early stage of osteonecrosis of femoral head.

Osteonecrosis of the femoral head (ONFH) is a painful and disabling condition, which most commonly involves the hips of young patients. But despite of the high incidence, treatment is still has not been definitely identified. We performed a modified muscle pedicle bone graft (MPBG) technique using anterior one-third of gluteus medius (GM) attached to the greater trochanter (GT) in ONFH. The purpose of this study was to evaluate the effectiveness of our technique on ONFH in ARCO stage II and III patients. Between June 2007 and March 2015, 24 hips were treated by our technique, who were able to follow up at least 2 years. The group was consisted of 15 men and 8 women, mean age of 36 years at the time of surgery. Mean follow-up was 5 years. Twenty of 24 hips hips had no progression of necrotic lesions. The postoperative scintigrams showed increased blood flow in the 3 month follow up evaluation. But 4 hips underwent THA at the mean follow-up of 6 years after the surgery, and considered as “failure”. Excluding the 4 failed cases, the mean Harris hip score was improved from 54 points to 85 points at the last follow up. Through our new technique, we showed 83% of survival rate by average of 5 year follow up. And compared to other reports, our technique showed relatively good survival rate and clinical outcomes. Therefore, we suggest this modified technique as one of promising treatment of choices for young patients with ARCO stage II or III ONFH

Introduction

Patients with osteonecrosis of the femoral head are typically younger, more active, and often require high rates of revision following primary total hip arthroplasty. However, outcomes of revision hip arthroplasty in this patient population have been rarely reported in the literature. The purpose of this study was to report the intermediate-term clinical and radiographic outcomes of revision hip arthroplasty in patients with osteonecrosis of the femoral head.

Introduction

The natural history of osteonecrosis of the femoral head (ONFH) is not cleanly understood, but most of them progresse to the joint destruction and requires total hip replacement arthroplasty. There are several head preserving procedure, but no single therapeutic method proved to be effective in preventing progression of the disease. The possibility has been raised that implantation of bone marrow containing osteogenic precursors may be effective in the treatment of this disease. However, there are no long-term follow-up results of cell therapy for ONFH. AS far as we know, there are no reports about bone graft and cell therapy for ONFH. Therefore, we performed a prospective clinical and radiological evaluation on ONFH treated with core decompression combined with autoiliac bone graft and an implantation of autologous bone marrow cells as a therapeutic method of ONFH.

Introduction

The pathophysiology of osteonecrosis of femoral head (ONFH) is uncertain for most cases with speculation of vascular impairment and changes in cell biology due to multi-factorial etiologies including corticosteroid, alcohol, smoking, trauma, radiation or caisson disease and genetic. Extracorporeal shockwave therapy (ESWT) began with an incidental observation of osteoblastic response pattern during animal studies in the mid-1980 that generated an interest in the application of ESWT to musculoskeletal disorders. The mechanism of shockwave therapy is not fully understood but several reports showed better clinical outcomes and promoted bone remodelling and regeneration effect of the femoral head after ESWT in ONFH. Therefore, we compared the clinical results of the use of extracorporeal shock wave therapy (ESWT) on the patients with ONFH in radiographic staging.

Introduction: It is desirable to delay or avoid total joint replacement in young patients who have osteonecrosis of femoral head. There are some head preserving surgical procedures that attempt this including osteotomy, core decompression, and bone grafting. The vascularized fibular graft has been reported to be a reliable procedure, but unfortunately it has donor site morbidity and is considered technically demanding. Therefore, materials have been developed to substitute for structural fibular graft. New trabecular metal has been developed to be used for osteonecrosis of femoral head. The purpose of this study was to review the clinical outcomes of trabecular metal as a treatment intervention method for osteonecrosis of the femoral head.

Materials and Methods: Seven patients (8 hips) with osteonecrosis of femoral head received core decompression and a trabecular metal implant, beginning in March 2003. The stage of osteonecrosis was I or II according to Ficat and Arlet except for one case (stage III). The procedure consists of a core decompression and insertion of trabecular metal rod (porous tantalum, Zimmer Inc./ Implex Incorporation). A Harris Hip Score was obtained pre-operatively, and at three and at three and six months. Radiographic data was collected at the same time of clinical follow-up.

Results: All 7 patients are doing well. Radiographic review shows no evidence of further femoral head collapse.

Discussion: Even though this is short term follow-up, the authors propose that the use of trabecular metal in osteonecrosis patients is simple, safe, and effective for the salvage of the hip.

Introduction and Objective. Osteonecrosis of the femoral head (ONFH) is an evolving and disabling condition that often leads to subchondral collapse in late stages. It is the underlying diagnosis for approximately 3%–12% of total hip arthroplasties (THAs) and the most frequent aetiology for young patients undergoing THA. To date, the pathophysiological mechanisms underlying ONFH remain poorly understood. In this study, we investigated whether ONFH without an obvious etiological factor is related to impaired osteoblast activities, as compared to age-matched patients with primary OA. Materials and Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head of patients with ONFH and from intertrochanteric region of patients with ONFH or with OA and compared their in vitro mineralisation capacity and secretion of paracrine factors. Results. Compared to patients with OA, osteoblasts obtained from the intertrochanteric region of patients with ONFH showed reduced mineralisation capacity, which further decreased in osteoblasts from the femoral head of the same patient. Lower mineralisation of osteoblasts from patients with ONFH correlated with lower mRNA levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. Osteoblasts from the intertrochanteric region of patients with ONFH secreted lower osteoprtegerin levels than those from patients with OA, resulting in a higher receptor activator of NF-κB ligand (RANKL)-to-osteoprotegerin (OPG) ratio. Notably, the RANKL-to-OPG ratio, as well as the secretion of the proresorptive factors interleukin-6 and prostaglandin E. 2. , was higher in osteoblasts from the femoral head of patients with ONFH than in those from the intertrochanteric region. Conclusions. ONFH is associated with a reduced mineralisation capacity of osteoblasts and increased secretion of proresorptive factors

Introduction: Proton magnetic resonance spectroscopy (¹H MRS) is a powerful non-invasive technique used to identify and quantify chemical compounds. In a recent study, the early histopathologic findings of osteonecrosis showed marrow edema and hemorrhage, and the late findings were fibrous marrow transformation with new bone formation. The purpose of this study was to apply ¹H MRS to the bone marrow of osteonecrosis and bone marrow edema syndrome by measuring the amount of lipid relative to water of the femoral head and greater trochanter.

Materials and Methods: Magnetic Resonance (MR) imaging and MR spectroscopy were performed in twenty-five patients (male: female = 17:8, age = 29–69 years) who were diagnosed with osteonecrosis and bone marrow edema syndrome and compared with three normal control patients. Twenty-three cases were osteonecrosis and two were bone marrow edema syndrome. Ficat stages of osteonecrosis in the femoral heads were 1 patient with stage I, 8 patients with stage II, and 14 patients with stage III disease. Osteonecrosis developed in 14 patients with steroid therapy after kidney transplantation, in 6 alcoholics, and 3 were idiopathic. After routine hip MRI, spectroscopy was obtained from T2 weighted images by the 3-dimensional localization technique. Locations of voxels were the center of the osteonecrotic zone verified by T2-weighted MR images and from the fat marrow in the greater trochanter of femur. The values of the [Lipid/Water] ratios were calculated for all patients.

Results: The average Lipid/Water ratio of the osteonecrotic area was 3.15, those of the greater trochanter was 6.45, compared with 10.28 in the normal control group. The MRS pattern for osteonecrosis could be divided into 4 patterns: A, Lipid/Water > 10 ; B, 3 < Lipid/Water ≤ 10; C, 0.3 ≤ Lipid/Water < 3; and D, Lipid/Water ≤ 0.3. The numbers of cases for each pattern were 1 in A, 6 in B, 10 in C, and 6 in D. Interestingly, in one patient with Ficat stage I osteonecrosis diagnosed by only bone scintigraphy, ¹H MR spectroscopy revealed a much higher lipid/water peak ratio compared to the normal control group. The average Lipid/Water ratio of the bone marrow edema syndrome patients was 0.71.

Discussion: This study revealed the decreasing pattern of lipid content as osteonecrosis progresses, which correlates with histopathologic results. In bone marrow edema syndrome, a reverse pattern to the normal control group was found. Further study is needed for the change of Lipid/Water ratio in early change of osteonecrosis.

The use of bisphosphonates in the treatment of avascular necrosis of the femoral head is an encouraging but relatively new option with most published data being derived from small trials with limited follow-up. We present a clinicoradiological analysis of 395 hips with avascular necrosis which were treated with oral alendronate for three years with a mean follow-up of four years (1 to 8). Our results show an improvement in the clinical function, a reduction in the rate of collapse and a decrease in the requirement for total hip replacement, compared with the findings of other studies in which no treatment was given. This improvement is particularly marked if the treatment is begun in the pre-collapse stages of the disease. Even in Ficat stage-III hips some benefit was obtained from treatment with alendronate by at least a delay in the need for total hip replacement

We performed 96 Birmingham resurfacing arthroplasties of the hip in 71 consecutive patients with avascular necrosis of the femoral head. A modified neck-capsule-preserving approach was used which is described in detail. The University of California, Los Angeles outcome score, the radiological parameters and survival rates were assessed. The mean follow-up was for 5.4 years (4.0 to 8.1). All the patients remained active with a mean University of California, Los Angeles activity score of 6.86 (6 to 9). Three hips failed, giving a cumulative survival rate of 95.4%. With failure of the femoral component as the endpoint, the cumulative survival rate was 98.0%. We also describe the combined abduction-valgus angle of the bearing couple, which is the sum of the inclination angle of the acetabular component and the stem-shaft angle, as an index of the optimum positioning of the components in the coronal plane. Using a modified surgical technique, it is possible to preserve the femoral head in avascular necrosis by performing hip resurfacing in patients with good results

The purpose of this study was to analyze the long-term effect of arterial perfusion of drugs and bone marrow stromal cells (bMSCs) on osteonecrosis of femoral head (ONFH). From Jan 1997 to Mar 2004, one hundred and seventeen patients with ONFH were consecutively enrolled to receive a digital subtraction angiography (DSA) in arteriae circumflexa femoris medialis and arteriae circumflexa femoris lateralis. In DSA, a dosage of drugs (urokinase, salvia injection, and tetramethylpyrazine) and autologous bMSCs or only the drugs were perfused into the arteries. The morphological changes of the arteries in DSA after perfusion were recorded. Symptoms radiographs, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at one month, six months, one year, 2 years and 5 years after the treatment. 83 patients were followed up for more than five years. The median follow-up period was 7.9 years.

After the drugs had been perfuse, the arteries became thicker, and more than 2 branches appeared in DSA. Five years after the operation, the Harris hip score of 32 patients (38 hips) treated by arterial perfusion of simplex drugs (group A) increased from 59.24±5.28 to 71.80±6.37 (p< 0.01), and the excellent and good rate of centesimal evaluation was 57.9%. The Harris hip score of 51 patients (59 hips) treated by arterial perfusion of drugs and autologous bMSCs (group B) increased from 59.52±4.85 to 78.29±6.05 (p< 0.01), and the excellent and good rate was 78.0% which was significantly higher than that of group A (p=0.035). Since two years after operation, the Harris hip score of group A was significantly higher than that of group B (p< 0.01).

Among the patients in group B, the rate of excellent and good in early stages (˜,˜ a and ˜ b according to Ficat classifying, 50 hips) was 84.0%, which was better than the rate in the terminal stage (Ficat III, 9 hips, the excellent and good rate was 44.4%)(p = 0.028), and the rate of excellent and good in low age group (< 40 years, 33 hips) was also better than that in high age group (≥ 40 years, 26 hips)(p=0.038).

We conclude that arterial perfusion of drugs and autologous bMSCs treating osteonecrosis of femoral head is safe and effective. The long-term therapeutic effect is more satisfactory than that of simplex arterial perfusion of drugs.

Osteonecrosis of the femoral head (ONFH) is an ischemic disorder that causes bone and bone marrow necrosis. In spite of many studies, the primary cause of ischemia is still unknown. The purpose of this study is to identify the susceptibility genes in ONFH. We performed a genome-wide association study (GWAS) in 1,602 ONFH cases and 60,000 controls. Stratified GWASs based on the 3 subgroups of ONFH (corticosteroids, alcohol, idiopathic) were also performed. We then evaluated the candidate gene in silico using public databases. Two loci in 12q24.11–12 and 20q12 showed significant association with ONFH. A stratified analysis suggested that the 12q24 locus was associated with ONFH through the drinking capacity. In the 20q12 locus, LINC01370 was the only gene, which functions were related to the plausible biological pathway for the development of ONFH. A novel ONFH locus was identified at chromosome 20q12, and LINC01370 was the best candidate gene in this locus

Of 24 intertrochanteric osteotomies for avascular necrosis of the femoral head, 22 were followed up for an average of 63 months. Sixteen of the 22 cases had good or excellent results, including 5 of the 6 cases with Stage II disease and 11 of the 16 with Stage III changes. Success seemed to be inversely related to the size of the lesion. There were six major orthopaedic complications, but despite these we feel that the operation has a definite role in the treatment of the young active patient

Haemophilia is a rare cause of avascular necrosis of the femoral head. We report three cases from one centre, an incidence of 2.8%. All three cases presented "silently", and this makes the early diagnosis difficult. Awareness of the condition should lead to examination of the hips of haemophiliac patients at every outpatient visit and admission in the hope that hip disease can be diagnosed at an early stage. This may allow earlier treatment, less femoral head deformity, and an improvement in the long-term prognosis

The pathophysiological basis of alterations in trabecular bone of patients with osteonecrosis of the femoral head (ONFH) remains unclear. ONFH has classically been considered a vascular disease with secondary changes in the subchondral bone. However, there is increasing evidence suggesting that ONFH could be a bone disease, since alterations in the functionality of bone tissue distant from the necrotic lesion have been observed. We comparatively studied the transcriptomic profile of trabecular bone obtained from the intertrochanteric region of patients with ONFH without an obvious aetiological factor, and patients with osteoarthritis (OA) undergoing total hip replacement in our Institution. To explore the biological processes that could be affected by ONFH, we compared the transcriptomic profile of trabecular bone from the intertrochanteric region and the femoral head of patients affected by this condition. Differential gene expression was studied using an Affymetrix microarray platform. Transcriptome analysis showed a differential signature in trabecular bone from the intertrochanteric region between patients with ONFH and those with OA. The gene ontology analyses of the genes overexpressed in bone tissue of patients with ONFH revealed a range of enriched biological processes related to cell adhesion and migration and angiogenesis. In contrast, most downregulated transcripts were involved in cell division. Trabecular bone in the intertrochanteric region and in the femoral head also exhibited a differential expression profile. Among the genes differentially expressed, we highlighted those related with cytokine production and immune response. This study identified a set of differently expressed genes in trabecular bone of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition.

Acknowledgements: This work was supported by grants PI18/00643 and PI22/00939 from ISCIII-FEDER, Ministerio de Ciencia, Innovación y Universidades (MICINN)-AES.

Osteonecrosis of the femoral head is a complex pathologic process with many aetiological factors. Factors most often mentioned in the literature are mechanical disruption (hip trauma or surgery), steroid use, smoking, haemoglobinopathies and hyperlipidaemia. 1. Our case depicts a rare association of crack cocaine related to osteonecrosis of the femoral head which has never been reported in the available literature. Case Report: A 32 year old man was referred to our Orthopaedic clinic with right hip pain. He had a 9 pack-year history of cigarette smoking and had also smoked crack cocaine between ages 20 to 28; shortly after this the hip pain started. He denied antecedent injury. He had undergone a steroid injection into his right ankle abroad for swelling one year before referral, which was after onset of hip pain. MRI of his hip previously performed abroad had been normal. The patient had an indoor job and was otherwise fit and well. On examination he had reduced of movement in his right hip with 5–10 degrees of fixed flexion deformity. Plain radiography demonstrated cyst formation and sclerosis of both femoral heads. Repeat MRI confirmed bilateral osteonecrosis, worse on the right with risk of head collapse. The patient underwent bilateral core decompressions. Subsequent follow-up demonstrated a mobile patient with no need for arthroplasty and he was discharged after two years. Osteonecrosis is caused by the coagulation of the intra-osseous microcirculation leading to thrombosis formation and eventual reduction in osseous blood supply. Steroid use is associated with increased risk of osteonecrosis to the femoral head, however in these cases the patients often undergo either direct local or systemic infiltration of steroid. In this case steroid was administered after symptoms began to a far distant site and therefore cannot be the cause. Cigarette smoking is also known to cause osteonecrosis. Our patient had smoked cigarettes for fourteen years without problems, and it was after he ceased to smoke crack cocaine that his symptoms began. Cocaine blocks voltage-gated sodium-channels causing vasospasm. It is known to cause nasal and facial bone osteonecrosis due to its common intranasal method of delivery. We postulate that in this case crack cocaine was a synergistic factor towards development of femoral head osteonecrosis

We studied the natural history of nontraumatic avascular necrosis of the femoral head (ANFH) in 115 hips in 87 patients, 69 steroid-induced, 21 related to misuse of alcohol and 25 idiopathic. The average length of follow-up was over five years. Collapse occurred most often when the focus of bone necrosis occupied the weight-bearing surface of the femoral head. Flatness of the head due to subchondral fracture was an early manifestation of collapse. Classification into six types based upon the radiographic findings provided an accurate prognosis for individual cases of ANFH which is useful in planning treatment and in assessing its outcome

We reviewed 41 hips in 40 patients at three to 11 years (average 6.3 years) after Sugioka transtrochanteric rotational osteotomy for non-traumatic avascular necrosis of the femoral head. The clinical results were excellent or good in 23 hips (56%) and the radiological success rate was 56%. Failure was due to fracture of the femoral neck, nonunion of the osteotomy, secondary collapse, or osteoarthritis. Nonunion and femoral neck fracture were more common after the use of the large screws described by Sugioka than with AO blade plates. Secondary collapse was significantly more common when less than one-third of the posterior articular surface was intact (p = 0.002). Postoperative degenerative changes were seen in cases with stage III avascular necrosis. We conclude that success depends to a large extent on the amount and stage of necrosis of the femoral head, but that careful technique and the use of AO hip plates may increase the likelihood of a satisfactory result

Introduction. Although osteonecrosis of the femoral head has been observed in young adult patients with autoimmune diseases such as SLE and MCTD that are treated by corticosteroids, the pathogenesis of the osteonecrosis remains unclear. We established a rat model with osteonecrosis of the femoral head by injecting lipopolysaccharide (LPS) and corticosteroid, and assessed consequences of the histopathological alteration of the femoral head, the systemic immune response, and the lipid synthesis. Methods. Male Wistar rats were given 2 mg/kg LPS intravenously on days 0 and 1 and intramuscularly 20 mg/kg methylprednisolone on days 2, 3, and 4. The animals were sacrificed 1, 2, 3, or 4 weeks after the last injection of the methylprednisolone. Histopathological and biochemical analyses were performed every week. The bone samples were then processed for routine hematoxylin and eosin staining to assess the general architecture and injury of the tissue. The triglyceride and the total cholesterol concentrations in the PRP were measured. The levels of various cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ, TNF-α) in blood samples were measured. Results. The body weight of the rats over time decreased for 2 weeks but had recovered by week 4. The plasma triglyceride concentrations had decreased significantly by weeks 2 and 3. The total plasma cholesterol concentrations had increased significantly by week 1 but then decreased significantly by week 4. The plasma concentrations of IL-1?α, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ and TNF-α had increased significantly by week 1. These cytokines can all be induced by toll-like receptor 4 (TLR4) signaling. We defined osteonecrosis as the diffuse presence of empty lacunae or pyknotic nuclei of osteocytes in the bone trabeculae, accompanied by surrounding bone marrow cell necrosis. Osteonecrosis of the femoral head was observed only in the epiphysis of the femoral head in sacrificed specimen every week. Histological analysis revealed osteocytic death surrounded by necrotic bone marrow with or without repaired tissue. Conclusion. We established a new rat model of corticosteroid-induced femoral head osteonecrosis. The necrosis that is generated in this model is similar to that seen in patients treated with corticosteroid. In particular, the necrotic lesion was exclusively observed in the proximal epiphysis. LPS is known to activate the immune system via the TLR4 signaling pathway. It has been recognized that the unique immunogenic effects of LPS promote autoimmune disease . LPS and methylprednisolone induced osteonecrosis of the femoral head in rats and this was associated with a disruption of the innate immune system and lipid synthesis. These findings suggest that the TLR4 signaling pathway plays an important role in the pathogenesis for osteonecrosis of the femoral head