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 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

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

Osteonecrosis of the femoral head after femoral neck fracture (ONFHpoFNFx) poses challenges in children, particularly at Ficat III stage. Limited effective treatments are available. This study explores basicervical femoral neck rotational osteotomy (BFNRO) for ONFHpoFNFx in children and adolescents and evaluates its outcomes. Children and adolescents with ONFHpoFNFx (Ficat stage III) underwent BFNRO at our center from June 2017 to September 2022 were included. Follow-up exceeded 1 year, with data on modified-Harris-hip-score (mHHS), range of motion (ROM), patient satisfaction, femoral head collapse, necrotic area repair, leg-length, and osteoarthritis progression recorded. This study included 15 cases (15 hips), with 8 males and 7 females, averaging 12.9 years in age (range: 10–17 years). Nine cases had BFNRO alone, and six had combined PAO. Rotation angles varied from 70° to 90° for anterior rotation and 110° to 135° for posterior rotation. Nine patients had femoral neck fixation in a varus position (10° to 30°). The postoperative contour of the weight-bearing area of the femoral head has significantly improved in all patients. With an average follow-up of 28.6 months (range: 12.2–72.7 months), mHHS significantly improved (65.2 to 90.2, P<0.001). Only one patient showed femoral head collapse. Patients experienced no/mild hip pain (VAS=0-3), slight restriction in range of motion, and mild limb shortening. Two patients showed osteoarthritis progression. No infections, joint replacements, or nerve injuries were observed. Even in cases of ONFHpoFNFx in the late stage, BFNRO in children and adolescents can still yield positive early to mid-term results by relocating the necrotic area and restoring the integrity of the anterior-lateral column of the femoral head, thereby preventing femoral head collapse and delaying the onset of severe osteoarthritis

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

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

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. 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

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

The clinical and pathological findings in a case of early avascular necrosis of the femoral head following renal transplantation are described. Regions of subchondral bone distant from the principal lesions showed increased numbers of empty osteocytic lacunae. This has been quantified and it is suggested that a loss of osteocytes is perhaps one of the earliest lesions leading to established avascular necrosis

Introduction: Osteonecrosis of the femoral head occurs in young patients. The preservation of the hip joint is vitally important because hip replacement arthroplasty is associated with high rates of failure in young and active patients. Curved intertrochanteric varus osteotomy is one of several joint preserving procedures used to treat these patients. Methods: Between June 2003 and June 2006, 46 patients (49 hips) who had osteonecrosis of the femoral head were treated with curved intertrochanteric varus osteotomy. There were 23 men and 23 women who had a mean age at the time of osteotomy was 33 years (range, 17 to 51 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 15 hips. Clinical evaluation was performed using the scoring system of Merle d’Aubigne et al. Radiological failure of the operation was defined as further collapse of the femoral head by more than 2 mm or progressive narrowing of the joint space compared with the immediate postoperative radiograph. Results: The mean duration of follow-up was 22 months (range, 12 to 48 months). One patient (one hip) required a total hip arthroplasty due to loss of fixation and penetration of the lag screw into the joint space. In two patients (two hips), the plate fractured at 3 and 4 months after the operation, which was changed to a new plate. Thus, 48 of the 49 hips survived at a mean follow-up 22 months. In these 48 hips, the mean Merle d’Aubigne hip score was 17.2 points at latest evaluation and there was no instance of radiologic failure. Discussion: Curved intertrochanteric varus osteotomy is a satisfactory joint preserving method to treat osteonecrosis of the femoral head

Introduction: Osteonecrosis of the femoral head, which involves the death of cells in trabecular bone and marrow, leads to fracture of subchondral bone and loss of the femur articulating surface in the hip and ultimately leads to total hip replacement (THR). Retrospective clinical studies show that osteonecrosis in 80–90% of affected patients inevitably progresses to destroy the femur head, usually within 2–3 years of diagnosis. None of the current treatment options are effective at terminating or reversing the disease process. Two reports (Hernigou and Beaujean, 2002 and Gangji, et al 2004) using fresh autologous bone marrow tissue injected directly into the necrotic femoral head, reported a high rate of success, especially in early stage osteonecrosis, in patients at most risk for disease progression. As a more standardized alternative to fresh bone marrow, Aastrom Biosciences has developed a proprietary automated process to expand autologous bone marrow cells. The ex vivo expanded cells referred to as Bone Repair Cells (BRC) are based on Aastrom Tissue Repair Cell (TRC) technology. BRC are a mixture of stem and early progenitor cells including cells of hematopoietic, mesenchymal, and endothelial lineages derived from a small sample of the patient’s own bone marrow. Materials and Methods: Fresh bone marrow mononuclear cells from normal donors were purchased from Poietics Inc. (Gaithersburg, Maryland) for BRC culture. After ex vivo expansion, BRC viability and cell phenotype characterization was performed by flow cytometry. The frequency of mesenchymal and hematopoietic stem cells within BRC was determined using CFU-F and CFU-GM assays. The osteogenic and vascular in vitro potential of BRC was measured using standard osteogenic differentiation assays and tube formation assays. The bone formation potential of BRC was determined using an ectopic bone formation model involving subcutaneous implantation. Based on the in vitro and in vivo potential of BRC, a mixing procedure was developed to implant BRC and bone matrix into osteonecrotic sites during standard core decompression surgery. The viability of BRC within the bone matrix was measured using standard cell metabolic assays. Results: BRC possess a diverse range of cell phenotypes with the potential to differentiate down the osteogenic and angiogenic lineage under the right conditions. BRC also has the potential for in vivo bone formation. In addition, examination of several cell-surface markers revealed a strong correlation between the frequency of cell surface markers CD105+, CD166+, CD90+ and in vivo bone formation scores when implanted with a ceramic matrix material. This BRC product can be mixed with a bone matrix for the implantation into long-bone defects or osteonecrotic sites without loss in cell viability. Discussion: Aastrom BRCs have both in vivo and in vitro bone and vascular potential; thus, it is our intent to demonstrate clinical safety and efficacy in treating osteonecrosis patients with BRC. Aastrom’s ON-CORE trial is a 120 patient Phase III clinical trial for the treatment of University of Pennsylvania radiographic classification stage IIb and IIc osteonecrosis patients. The primary efficacy endpoint of this trial is to delay disease progression of osteonecrosis to fracture for at least 24 months post-treatment, and potentially prevent collapse of the femur head, which will be measured by a blinded third-party reviewer through magnetic resonance imaging. Patients will be followed for a total of 5 years, post-treatment

Of 899 patients with sickle-cell disease, aged between 6 and 28 years, who attended clinics in the Guinea Savannah of Nigeria in 1982 and 1983, 29 had symptoms of avascular necrosis of the femoral head. This group was studied in detail. Twenty-eight patients had haemoglobin-SS electrophoretic patterns and one had haemoglobin-SC. The male to female ratio was 1 to 1.6, and most of the patients were aged between 6 and 15 years at the onset of hip symptoms. These symptoms correlated with the radiographic lesions, but were not related to the age or sex of the patient. The radiographic lesions varied widely and were related to the age at onset of hip symptoms. A new radiological classification is proposed

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

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.

We have reviewed 54 hips in 46 patients from 2 to 14 years after a joint-preserving operation for idiopathic avascular necrosis of the femoral head. The choice between core decompression (17 hips), bone grafting (18), rotation osteotomy (15) or varus osteotomy (4) was determined by the stage and location of the area of necrosis. The overall success rate was unexpectedly low at 60%. Core decompression and bone grafting by our techniques gave poor long-term results, but those of rotation or varus osteotomies, performed with care for the correct indications, were better. The indications for each procedure are discussed: osteotomy is best when the area of necrosis is shallow and localised in the medial or anterior portion of the femoral head

Twenty-nine patients with avascular necrosis of the femoral head after injury have been treated by operation. Multiple drilling of the femoral head was performed, necrotic bone removed and a muscle-pedicle bone graft implanted into the head and neck of the femur. In 17 of the patients the necrosis was associated with an un-united femoral neck fracture, in 11 it occurred after the fracture had united, and one case followed reduction of a dislocated hip. The hips became painless soon after operation. The patients were young (average age 35 years), and full weight-bearing was not allowed for several months. The follow-up period ranged from 22 to 64 months. The results were excellent in 20 patients, good in five, fair in three and poor in one