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 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

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

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

Introduction. Osteonecrosis of the femoral head occurs in young patients. The preservation of the hip joint is vitally important, because hip arthroplasty does not guarantee satisfactory long-term results in young and active patients. Curved intertrochanteric varus osteotomy is one of several joint preserving procedures used for this disease. Methods. Between June 2004 and June 2007, 52 patients (55 hips) who had osteonecrosis of the femoral head were treated with curved intertrochanteric varus osteotomy. There were 29 men and 23 women who had a mean age at the time of osteotomy of 33 years (range, 18 to 52 years). The osteotomy was fixed with a 120 degree compression hip screw in the first 34 hips and with a 95 degree dynamic condylar screw in the remaining 21 hips. Clinical evaluation was performed using the scoring system of Merle d'Aubigne et al. Results. The mean duration of follow-up was 32 months (range, 24 to 60 months). Six patients (six hips) required a total hip arthroplasty, due to loss of fixation in two hips, shortening of the operated limb in two hips, and further collapse with persistent pain in two hips. In two patients (two hips), the plate fractured at 3 and 4 months after the operation, which was changed to a new plate. Thus, 49 of the 55 hips survived at a mean follow-up 32 months. In these hips, the mean Merle d'Aubigne hip score was 17.4 points at the latest evaluation. Conclusion. Curved intertrochanteric varus osteotomy is a satisfactory joint preserving method to treat osteonecrosis of the femoral head

Total hip arthroplasty (THA) outcome in patients with osteonecrosis of the femoral head ONFH) are excellent, however, there is controversy when compared with those in patients with osteoarthritis (OA). Reduced mineralization capacity of osteoblasts of the proximal femur in patients with ONFH could affect implant fixation.

We asked if THA fixation in patients with ONFH is worse than in those with OA.

We carried out a prospective comparative case (OA)-control (ONFH) study of patients undergoing THA at our hospital between 2017 and 2019. The minimum follow-up was 2 years. Inclusion criteria were patients with uncemented THA, younger than 70 years old, a Dorr femoral type C and idiopathic ONFH. We compared the clinical (Merlé D'Aubigné-Postel score) and radiological results related with implant positioning and fixation. Engh criteria and subsidence were assessed at the immediate postoperative, 12 weeks, 6 months, 12 months and yearly. Osteoblastic activity was determined by mineralization assay on primary cultures of osteoblasts isolated from trabecular bone samples collected from the intertrochanteric area obtained during surgery.

Group 1 (ONFH) included 18 patients and group 2 (OA), 22. Average age was 55.9 years old in group 1 and 61.3 in group 2. (p=0.08). There were no differences related with sex, Dorr femoral type or femoral filling. The mean clinical outcome score was 17.1 in group 1 and 16.5 in group 2 (p=0.03). There were no cases of dislocation, infection, or revision surgery in this series. There were 5 cases (28%) of femoral stem subsidence greater than 3mm within 6 first months in group 1 and 1 case (4.5%) in group 2 (p=0.05).

Although there were no significant differences related to clinical results, bone fixation was slower, and a greater subsidence was observed in patients with ONFH. Greater femoral stem subsidence was associated with a lower capacity for mineral nodule formation in cultured osteoblasts. The surgical technique could influence THA outcome in patients with reduced mineralization capacity of osteoblasts.

Introduction. Osteonecrosis of the femoral head usually progresses to collapse in up to 70% to 80% of all cases. Previous studies have shown high failure rates with non-operative treatment, whereas, some surgical options including bone grafting, core decompression, osteotomy and arthroplasty have been recommended. Total hip arthroplasty and hemiarthroplasty, either cemented or cementless, are the last resort for improving the functional outcomes for the elderly. However, salvage of the femoral head in relatively young patients is widely advocated. Thus vascularized bone grafting has been recommended to salvage the collapsing femoral head. The purpose of this study was to evaluate the prognostic factors related to the outcome of the vascularized iliac bone grafting in the treatment of osteonecrosis of the femoral head. Methods. A retrospective case series review study is presented. Between April 1987 and April 2003, 47 patients (51 hips) in the authors' hospital underwent vascularized iliac bone grafting for the treatment of osteonecrosis of the femoral head. Three patients were lost to follow-up, thus, 44 patients (48 hips), 38 men and 4 women, were included in the study. All patients underwent operation by one experienced senior surgeon. Patients were grouped according to related risk factors, i.e., trauma, corticosteroid, alcohol, and an idiopathic group. A radiographic scale, the Ficat and Arlet classification system, was used for grading the osteonecrosis. We set the conversion to total hip arthroplasty as the end point for survival of vascularized iliac bone grafting in this study. Kaplan-Meier survivorship analysis was used to determine the significance with regard to the risk factors, age, Ficat and Arlet staging, gender, and side. Results. The Kaplan-Meier survivorship analysis showed that the 5-year overall rate of graft survival was 68.5% (95% confidence interval: 52.7% to 80.0%), 10-year overall rate of graft survival was 61.5% (95% confidence interval: 44.4% to 74.8%), and 61.5% (95% confidence interval: 44.4% to 74.8%) at 15 years. There was no significant difference between the groups regarding the prognostic factors of etiology, gender, side, and stage. The only significant parameter was the age that the patients older than 50 years had the worst 5-year survival rate of the femoral head (p<0.05). Conclusion. Vascularized bone grafting is a technically demanding procedure when compared to conventional core decompression or arthroplasty. However, this technique can preserve the femoral head from collapse and preclude the need for arthroplasty in young patients

Introduction

For many years, minimally invasive joint-preserving regenerative therapy has been desired for the early stages of osteonecrosis of the femoral head (ONFH). In an animal study using adult rabbits, we reported that a single local injection of rhFGF-2-impregnated gelatin hydrogel, which has superior slow-release characteristics, suppresses the progression of femoral head necrosis. The purpose of this study was to evaluate the safety and clinical outcomes of a single local administration of rhFGF-2-impregnated gelatin hydrogel for the precollapse stage of ONFH. Patients and Methods: Ten patients with femoral heads up to precollapse stage 2 underwent a single local administration of 800-µg rhFGF-2-impregnated gelatin hydrogel and were followed up for two years. The eligibility criteria were age between 20 and 80 years and presence of ONFH at precollapse stage 1 or 2 according to the classification system for ONFH developed by the Japanese Investigation Committee of Health and Welfare. Primary outcomes included adverse events and complications. Secondary outcomes included changes in Harris Hip Scores (HHS), visual analog scale pain scores (VAS), the University of California, Los Angeles (UCLA) activity rating scores, radiological changes as determined via radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI) of the hip joint. Results: We included five men (five hips) and five women (five hips), with a mean age of 39.8 years (range: 29–53 years) at the time of surgery. Eight patients had bilateral ONFH, three had already undergone THA on the contralateral side. Eight patients were receiving treatment with corticosteroid therapy, and two patients overused alcohol. Stage 1 and 2 disease was present in one and nine patients, respectively. One patient each had type A, type B, and type C1 disease, whereas seven patients had a type C2 lesion. All Adverse events were recovered without problem. The surgery was performed with a minimally invasive technique based core decompression (1 cm of skin incision), and walking was allowed from the day after surgery. Mean clinical scores improved significantly after three year compared with before surgery (before vs. after: VAS for pain, 21.2 vs. 5.3 mm; UCLA activity score 5.5 vs. 6.6; HHS, 81.0 vs. 98.4 points, respectively). There was only one case of femoral head collapse, and it had the greatest necrosis volume fraction and was considered to be in the early collapse stage at the time of operation. The other nine cases did not involve ONFH stage progression, and collapse was prevented. CT images and recent MRI postoperatively confirmed bone regeneration and reduction of the necrotic area. Conclusion: Clinical application of rhFGF-2-impregnated gelatin hydrogel for patients with precollapse stage of ONFH was feasible and safe. Our research is ongoing, further phase II multiple center study has been started in January 2016.

Introduction

The crescent sign is thought to be an early indicator of collapse in osteonecrosis of the femoral head. However, the formation mechanism of the crescent sign is still not quite clear. The purpose of this study was to utilize the two-dimensional finite element model analysis (FEA) technique to analyze mechanical function of different structures and intraosseous fluid in the femoral head under the stress of physiological loading. We wished to answer the following question: which structure or structures' failure are the main causes of collapse in osteonecrosis of the femoral head (ONFH)?

Introduction

Even in localized collapse due to osteonecrosis of the femoral head, a femoral head can be preserved by rotational osteotomy. In addition to anterior rotation, originally described by Sugioka, much more correction can be obtained by posterior rotation. But, transtrochanteric rotational osteotomy needs rather extensive soft tissue release, such as complete capsulotomy and resection of short external rotators and psoas tendons. Many patients tend to complain about the leg length discrepancy and limp due to varus change. We found soft tissue resection and limb shortening could be minimized by doing the osteotomy at the femur neck rather than the trochanteric area following the technique of surgical dislocation. It needs careful dissection of the posterior retinacular artery to preserve circulation to the femoral head.

Introduction

Hip resurfacing has become a popular procedure for young active patients with osteonecrosis of the femoral head. However, it is not yet clear exactly how much osteonecrosis would permit this procedure and how much would be a contraindication. The aim of the present study was to analyze the resurfaced femoral head using finite element models and, in particular, to examine the influence of the extent of osteonecrosis and metaphysical stem shaft angles within the femoral head.

Introduction

Since 2005, we have performed implantation of bone marrow-derived mononuclear cells for osteonecrosis of the femoral head in order to improve vascularization and bone repair. This study focused on early bone repair of osteonecrosis of the femoral head after transplantation of bone marrow-derived mononuclear cells (BMMNC).

Introduction

In osteonecrosis of the femoral head (ONFH), progression of collapse is influenced by a repair reaction, especially bone resorptive activity, around the necrotic bone. Alendronate is a potent inhibitor of bone resorption by inhibiting osteoclast activity. We performed a clinical study to test if systemic alendronate treatment would prevent the development of collapse in patients with ONFH.

Introduction

Transtrochanteric curved varus osteotomy is one of the effective joint-preserving operations for osteonecrosis (ON) of the femoral head. We correlated various factors with the radiological outcome of this procedure.

Introduction

The purpose of this study was to investigate the long-term outcome of Sugioka's transtrochanteric rotational osteotomy (TRO) for nontraumatic osteonecrosis of the femoral head.

Introduction

The treatment osteonecrosis of the femoral head remains uncertain. Core decompression is the standard technique for the early stages (ARCO I and II). A new alternative is core decompression combined with the insertion of an osteonecrosis rod. This implant is supposed to reduce the intraosseous pressure and to give additional structural support. The aim of this study was to evaluate the clinical and radiological outcome via magnetic resonance imaging (MRI) of this new technique.

Introduction

What is the most effective treatment of the early stages for osteonecrosis of the femoral head? Since the results of several treatment modalities such as multiple drilling, core decompression with or without bone graft, and vascularized fibular grafts have not been completely successful, we tried multiple drilling and stem cell transplantation to treat the early stages of osteonecrosis of the femoral head and to minimize patient morbidity. We report the clinical and radiological results of stem cell transplantation and core decompression.

Introduction

The purpose of this study was to evaluate the outcome of vascularized iliac bone grafting for idiopathic osteonecrosis of the femoral head.

Introduction

The purpose of this study was to evaluate the functional and radiographical mid-term follow-up results of a second generation metal-on-metal cementless total hip arthroplasty for the treatment of osteonecrosis of the femoral head in patients younger than 50 years.