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

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: 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

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

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.

Background

Surgical treatment for osteonecrosis of the femoral head (ONFH) includes both joint-preserving techniques and joint replacement. Joint preservation is more effective in early-stage ONFH; thus, prompt diagnosis when the femoral head is still salvageable is an important clinical goal. We report a 20-year retrospective study that summarizes the proportion of patients diagnosed with early-stage versus late-stage ONFH at initial presentation to our practice.

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

Symptomatic hip osteonecrosis is a disabling condition with a poorly understood aetiology and pathogenesis. Numerous treatment options for hip osteonecrosis are described, which include non-operative management and joint preserving procedures, as well as total hip replacement (THR). Non-operative or joint preserving treatment may improve outcomes when an early diagnosis is made before the lesion has become too large or there is radiographic evidence of femoral head collapse. The presence of a crescent sign, femoral head flattening, and acetabular involvement indicate a more advanced-stage disease in which joint preserving options are less effective than THR. Since many patients present after disease progression, primary THR is often the only reliable treatment option available. Prior to the 1990s, outcomes of THR for osteonecrosis were poor. However, according to recent reports and systemic reviews, it is encouraging that with the introduction of newer ceramic and/or highly cross-linked polyethylene bearings as well as highly-porous fixation interfaces, THR appears to be a reliable option in the management of end-stage arthritis following hip osteonecrosis in this historically difficult to treat patient population.

Cite this article: Bone Joint J 2013;95-B, Supple A:46–50.

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

A staging system has been developed to revise the 1994 ARCO classification for ONFH. The final consensus resulted in the following 4-staged system: stage I—X-ray is normal, but either magnetic resonance imaging or bone scan is positive; stage II—X-ray is abnormal (subtle signs of osteosclerosis, focal osteoporosis, or cystic change in the femoral head) but without any evidence of subchondral fracture, fracture in the necrotic portion, or flattening of the femoral head; stage III—fracture in the subchondral or necrotic zone as seen on X-ray or computed tomography scans. This stage is further divided into stage IIIA (early, femoral head depression ≤2 mm) and stage IIIB (late, femoral head depression >2 mm); and stage IV—X-ray evidence of osteoarthritis with accompanying joint space narrowing, acetabular changes, and/or joint destruction. Radiographs, magnetic resonance imaging (MRI), and computed tomography (CT) scans may all be involved in diagnosing ONFH; however, the optimal diagnostic modality remains unclear. The purpose of this study was to identify: 1) how ONFH is diagnosed at a single academic medical center, and 2) if CT is a necessary modality for diagnosing/staging OFNH.

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

Introduction: Osteonecrosis of the femoral head (ONFH), a disease of unknown pathogenesis usually involves subchondral bone and shows an improper repair process. The temperature of the subchondral bone of the femoral head was found to increase by a maximum of 2.5 °C in a simulation of walking performed in cadavers. A greater increase in the temperature is expected in the necrotic bone in ONFH because there is no heat dissipation by blood flow. The purpose of this study was to confirm the possibility that hyperthermia is a cause of the poor regeneration of the necrotic bone in ONFH. Materials and Methods: Necrotic and living bone extracts were prepared from the femoral heads of 4 ONFH patients. Human umbilical vein endothelial cells (HUVECs) were cultured with endothelial cell growth media-2 (EGM-2), EGM-2 supplemented with necrotic bone extracts, and EGM-2 supplemented with living bone extracts. HUVECs were also cultured at temperatures of 40, 40.5, 41 and 42 °C, while controls were maintained at 37 °C. Viable cell numbers of HUVECs were determined by MTS assay at days 1, 4, 6, 8, and 11. Results: The number of viable cells decreased in hyperthermic conditions of 40.5 to 42 °C (p< 0.05). The addition of living bone extracts induced a significant increase in the number of viable cells during the culture periods (p< 0.05). Necrotic bone extracts did not induce such a significant increase. Discussion: Local subchondral hyperthermia might be a possible cause of the poor regeneration of the necrotic area in ONFH

We have studied core biopsy specimens from 16 femoral heads affected by idiopathic avascular necrosis at the silent stage, when there were no clinical or radiographic manifestations but scintigraphy was positive. All the specimens showed necrosis of trabeculae and of bone marrow, but the most common and characteristic feature was evidence of old and new haemorrhage in the marrow. In the areas of intramedullary haemorrhages, trabeculae and bone marrow were completely necrotic, with a transitional area of incomplete necrosis between these areas and those without haemorrhagic lesions, where the trabeculae and bone marrow were normal. There was good correlation between necrosis and haemorrhagic episodes, and it was concluded that repeated intramedullary haemorrhage at the silent stage is probably related to the pathogenesis of idiopathic avascular necrosis of the femoral head

Introduction

The purpose of this study was to analyze trends in the surgical management of ON in recent years. Specifically, we evaluated the annual prevalences of: 1) joint preserving procedures (osteotomies and core decompression/grafts) and 2) joint non-preserving procedures (total hip arthroplasties [THAs], revision THAs, partial THAs) for the treatment of osteonecrosis of the femoral head (ONFH) between 2009 and 2016.

The purpose of this study was to compare the clinical and radiological findings in patients with avascular necrosis of the femoral head after management with vascularized fibular graft (VFG) compared to porous tantalum implant. The study included 60 hips in 50 patients, who were followed prospectively for 2–4 years. 28 patients (30 hips) were treated with VFG and 22 patients (30 hips) were treated with a porous tantalum implant. The two patient groups were matched for age, gender, etiology, pre-operative stage and Harris Hip Score (HHS). Of the VFG group, 14 hips were stage II and 16 were stage III, while of the tantalum group, 1 hip was stage I, 11 hips were stage II and 18 hips were stage III, according to Steinberg classification system. Mean operative time was 3 hours for VFG and 30 min for porous tantalum. At final follow-up, there was no significant statistical difference in the radiological stage (p=0.246), and radiological progression of the disease (p=0.329) was observed between these two groups. Using HHS, the mean clinical results improved in the VFG group from 61 points preoperatively to 90 points at final follow-up, while in tantalum group HHS improved from 63 to 81 points (p=0.022). Three hips from each group underwent total hip arthroplasty. The results of the present study suggest that although the management of AVN with VFG appears to show better results compared to the use of porous tantalum using clinical evaluation Methods: (eg HHS), further controlled studies with larger patient groups and longer follow-up are required

There is a high risk of the development of avascular necrosis of the femoral head and nonunion after the treatment of displaced subcapital fractures of the femoral neck in patients aged < 50 years. We retrospectively analysed the results following fixation with two cannulated compression screws and a vascularised iliac bone graft. We treated 18 women and 16 men with a mean age of 38.5 years (20 to 50) whose treatment included the use of an iliac bone graft based on the ascending branch of lateral femoral circumflex artery. There were 20 Garden grade III and 14 grade IV fractures. Clinical and radiological outcomes were evaluated. The mean follow-up was 5.4 years (2 to 10). In 30 hips (88%) union was achieved at a mean of 4.4 months (4 to 6). Nonunion occurred in four hips (12%) and these patients had a mean age of 46.5 years (42 to 50) and underwent revision to a hip replacement six months after operation. The time to union was dependent on age with younger patients achieving earlier union (p < 0.001). According to the Harris hip score which was available for 27 of the 30 hips with satisfactory union, excellent results were obtained in 15 (score ≥ 90 points), fair in ten (score 80 to 90 points), and poor in two hips (≤ 80 points). One patient aged 48 years developed avascular necrosis of femoral head six years after operation and underwent total hip replacement.

The management of displaced subcapital fractures of the femoral neck, in patients aged <  50 years, with two cannulated compression screws and an iliac bone graft based on the ascending branch of lateral femoral circumflex artery, gives satisfactory results with a low rate of complication including avascular necrosis and nonunion.

Cite this article: Bone Joint J 2014;96-B:1024–8.

Purpose: The purpose of this retrospective study was to assess clinical and radiological outcome at ten years follow-up at least in a continuous series of total hip arthroplasties performed in patients with aseptic necrosis of the femoral head. Material and methods: The series included 122 arthroplasties performed between January 1980 and December 1996 in 96 patients (26 women and 70 men), aged 50.8±13.3 years (range 21–85 years). The underlying cause was essential necrosis in 40.6%, cortocosteroid threapy in 19.8%, chronic alcoholism for 17%, trauma for 12%, and another medical cause for 10%. The Ficat and Arlet classification was grade IV 80 hips, grade III 42 hips. All arthroplasties were performed via the transtrochanteric approach. Cemented Charnley-Kerboull implants were used with a metal-polyethylene couple in all cases. The Merle d’Aubigné score was used to assess functional outcome. Cup wear was measured according to Livermore. Actuarial survival curves were calculated. Results: Follow-up was greater than ten years for all patients (mean 13±2.6 years, range 10–21 years). At last follow-up 59 patients (75 hips) were living and had not undergone revision and seven patients (seven hips) had undergone revision of the acetabular and/or femoral component. Twenty patients (24 hips) had died and ten patients (16 hips) were lost to follow-up. Revision procedures were performed for periacetabular osteolysis in one hip, infection in one hip, and acetabular loosening in five hips. Three patients experienced luxation or subluxation. The mean preoperative function score was 11 (range 5 – 16) compared with 17 (14–18) at last follow-up (p < 0.05). Clinical outcome was good or excellent in 95% of the patients and fair or poor in 5%. Mean overall cup wear was 0.965 mm (0–5) for non revised hips. Lucent lines were found around eleven acetabular implants and six femoral implants. Cumulative survival, considering revision as failure, was 88.5% at 15 years (95% confidence interval 80.2 – 96.9%). Discussion and conclusion: The results of this series lead to the conclusion that low-friction total hip arthroplasty is the treatment of choice for advanced stage femoral head necrosis

Introduction

Without intervention 80% of hips with osteonecrosis (ON) will progress. Core decompression has shown favorable results (60–80% survivorship) in early stage ON, and recently, bone marrow aspirate concentration (BMAC) injection into the decompressed femoral head has been proposed to stimulate healing of the necrotic lesion and improve outcomes and survivorship.

Introduction: Osteonecrosis of the femoral head remains a challenging problem especially in young patients. The purpose of this study was to evaluate the clinical results of a viable iliac bone graft for treating osteonecrosis of the femoral head. Materials and Methods: Seventy-one hips in 52 patients underwent a viable iliac bone graft (9 hips-vessel pedicle iliac bone graft and 62 hips-muscle pedicle iliac bone graft). The clinical and radiographic results were evaluated after an average of 3 years and 4 months (range, 2 to 5 years). Patient age ranged from 20 to 40 years with an average of 31 years. Twenty-three hips were classified as Ficat stage 2 disease and 48 as stage 3 disease. The causes of osteonecrosis were excessive alcohol consumption in 30, steroid use in 13, posttraumatic in 4, decompression sickness in 1, and unknown in 23 hips. The clinical results were evaluated based on the patients’ satisfaction and pain score. The radiographical results were evaluated by serial follow-up roentgenography and pinhole bone scintigraphy. Results: The clinical and radiological results were satisfactory. Overall, the survival rate was 96 percent. Excellent results were obtained in 15 hips, good in 39, fair in 6 and poor in 8. Three hips underwent total hip replacement, including one infected case. Excellent or good results were obtained in 82 percent of stage 2 cases and in 65 percent of stage 3 cases. The serial roentgenographic examination revealed a gradual incorporation of the grafted bone, and the scintigraphic examination revealed a gradual increase in the uptake which suggested an increased blood supply to the femoral head. Discussion: The overall results of viable iliac crest bone grafting were very satisfactory. This technique is recommended particularly for young patients with stage 2 or 3 osteonecrosis of the femoral head. Pinhole bone scintigraphy was quite useful for evaluating the healing process after the revascularization procedure

Post-traumatic osteonecrosis of the femoral head (ONFH) is a major complication of femoral neck fractures that require numerous solutions. The purpose of the current study is to investigate the effects of platelet-rich plasma (PRP) incorporated autologous granular bones graft for the treatment of pre-collapse stages (ARCO stage II-III) of post-traumatic ONFH.

A total of 46 patients were eligible and enrolled into the study. 24 patients were treated with core decompression and PRP incorporated autologous granular bones graft (treatment group: 9 females and 15 males, age range, 16–39 years), and 22 patients with core decompression and autologous granular bones graft (control group: 6 females and 16 males, age range, 18–42 years. During a minimum duration of follow-up of 36 months, multiple imaging techniques including X-ray and computed tomography (CT) scanning were used to evaluate the radiological results, and Harris hip score (HHS) and the visual analogue scale (VAS) were chosen to assess the clinical results.

Both treatment group and control group had a significant improved HHS (P < 0.001). The minimum clinically important difference (MCID) for HHS was reached in 91.7% of treatment group and 68.2% of control group (P = 0.0449). HHS in treatment group was significantly higher than control group at the last follow-up (P = 0.0254). VAS score was significantly declined in treatment group when compared with control group (P = 0.0125). Successful clinical results were achieved in 21 of 24 patients (87.5%) in treatment group compared with 13 of 22 patients (59.1%) in control group (P = 0.0284). Successful radiological results were achieved in 19 of 24 patients (79.2%) in treatment group compared with 11 of 22 patients (50%) in control group (P = 0.0380). The survival rates using requirement for further hip surgery as an endpoint were higher in treatment group in comparison to control group (P = 0.0260).

The PRP incorporated autologous granular bones graft is a safe and effective procedure for the treatment of pre-collapse stages (ARCO stage II-III) of post-traumatic ONFH.

We evaluated the outcome of treatment of nonunion of an intracapsular fracture of the femoral neck in young patients using two cannulated screws and a vascularised bone graft. A total of 32 patients (15 women and 17 men, with a mean age of 36.5 years; 20 to 50) with failed internal fixation of an intracapsular fracture were included in the study. Following removal of the primary fixation, two cannulated compression screws were inserted with a vascularised iliac crest bone graft based on the ascending branch of the lateral femoral circumflex artery.

At a mean follow-up of 6.8 years (4 to 10), union was achieved in 27 hips (84%). A total of five patients with a mean age of 40.5 years (35 to 50) had a persistent nonunion and underwent total hip arthroplasty as also did two patients whose fracture united but who developed osteonecrosis of the femoral head two years post-operatively. Statistical analysis showed that younger patients achieved earlier and more reliable union (p < 0.001). The functional outcome, as assessed by the Harris Hip score, was better in patients aged < 45 years compared with those aged > 45 years (p < 0.001).

These findings suggest that further fixation using two cannulated compression screws and a vascularised iliac crest bone graft is an effective salvage treatment in patients aged <  45 years, in whom osteosynthesis of a displaced intracapsular fractures of the femoral neck has failed.

Cite this article: Bone Joint J 2015; 97-B:988–91.

We present the long-term results of simple varus intertrochanteric osteotomy for osteonecrosis of the femoral head. We followed 26 hips in 20 patients, with a mean age at the time of surgery of 36 years, for a mean of 12.5 years. The mean varus angulation was 23°.

The outcome in 19 of the hips (73%) was good or excellent; seven (27%) had a fair or poor result, with four needing some form of prosthetic arthroplasty.

Simple varus intertrochanteric osteotomy is indicated, even if the extent of the capital infarct comprises more than 50% of the diameter of maximum radial distance from the circumference, provided that after operation the medial necrotic lesion measures less than two-thirds of the weight-bearing area, and the superolateral bone is normal.

We performed a prospective study using MRI to evaluate early necrosis of the femoral head in 48 patients receiving high-dose corticosteroids for the treatment of various autoimmune-related disorders. The mean interval from the initiation of corticosteroid therapy to the first MRI examination was 2 months (0.5 to 6). MRI was repeated, and the mean period of follow-up was 31 months (24 to 69).

Abnormalities were found on MRI in 31 hips (32%). The initial changes showed well-demarcated, band-like zones which were seen at a mean of 3.6 months after initiation of treatment with steroids. In 14 of these hips (45%) there was a spontaneous reduction in the size of the lesions about one year after treatment had started, but there was no further change in size with a longer follow-up.

Introduction

In early stage osteonecrosis of the femoral head (ONFH), core decompression (CD) is often performed; however, approximately 30% of CD cases progress to femoral head collapse. Bone healing can be augmented by preconditioning MSCs (pMSCs) with inflammatory cytokines. Another immunomodulatory approach is the timely resolution of inflammation using cytokines such as IL-4. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on steroid-associated ONFH in rabbits.

Objectives

The purpose of the present study was to describe the long-term results of THA for ONFH in patients with SLE.

Introduction: Osteonecrosis of the femoral head (ONFH) has a close association with corticosteroid therapy. As corticosteroids are accepted to be metabolized mainly by CYP3A4 in the liver, low constitutive levels of the enzyme might lead to an excessive response to corticosteroids and lead to adverse events including bone necrosis. This clinical study was designed to elucidate this hypothesis and to present potential modalities to avoid corticosteroid-associated ONFH by tailoring the steroid dose according to individual metabolic capacities of corticosteroid. Materials and Methods: Twenty-two steroid-associated ONFH patients, 27 alcohol-related ONFH patients, and 65 general population controls were enrolled in this study. To estimate functional level of hepatic CYP3A4 level, a midazolam (MDZ) clearance test was carried out in respective subjects. The results from the tests were compared between those groups. Results: The distribution profile of the MDZ clearance in steroid-associated ONFH patients were shifted to the left, indicating lower hepatic CYP3A4 activity in those patients when compared with the general population. By using an unconditional logistic regression model, patients with low (< 9.7) MDZ clearance due to low hepatic CYP3A4 activity were at 9.5 times greater risk for corticosteroid-induced ONFH compared with those with high (9.7+) MDZ clearance (OR 9.5 [95% CI 2.79–32.2], p< 0.001). The hepatic CYP3A4 activity was not associated with prevalence of alcohol-associated ONFH. Discussion: A significantly low constitutive hepatic CYP3A4 function in corticosteroid-associated ONFH patients was found. The corticosteroid-associated ONFH might result from excessive responsiveness to corticosteroids in those patients due to prolonged exposure of bone to high levels of corticosteroids because of low functional level of the steroid metabolizing enzymes. The steroid-associated ONFH might be avoided by tailoring the corticosteroid dose in accordance with the functional level of hepatic CYP3A4

Introduction: The treatment of asymptomatic osteonecrosis of the femoral head (ONFH) is controversial. The primary aim of this study was to define the optimal management of osteonecrotic lesions in patients with asymptomatic ONFH by determining the incidence of disease progression and the factors that might predict its occurrence. In order to assess the indications and timing for surgical intervention in these patients, the secondary aim was to determine whether or not pain precedes subchondral fracture in patients with asymptomatic disease.

Methods: The subjects in this study were patients with asymptomatic ONFH who were derived from two separate prospective, institutional review board-approved investigations in our institution. We determined the incidence of pain development and radiographic evidence of fracture and the temporal relationship of these events. Statistical analyses were performed to determine what factors affected either radiographic progression or the appearance of symptoms.

Results: Of the 37 hips, 12 (32%) were symptomatic at 2 years. Of these painful hips, six (50%) were associated with the simultaneous presence of a subchondral fracture. When analyzing the relationship of pain with fracture, 5 of 6 hips developed symptoms at an average of 8.1 months (1 to 28 months) prior to fracture. Three symptomatic patients had spontaneous resolution of the ONFH. Cox regression analysis revealed that an index of necrosis of > 50 and a greater extent of radiographic involvement correlate with a higher risk for developing symptoms and a subchondral fracture. If an index of necrosis of 50 is set as the lower limit for intervention, 78% of hips that fractured and 93% of hips that did not were identified.

Discussion: Asymptomatic ONFH with small lesions are amenable to observation, and intervention may be withheld until the appearance of symptoms. Asymptomatic ONFH with extensive femoral head involvement has a high probability of early progression to symptomatic ONFH and subchondral fracture. In these cases, early intervention may be beneficial in preventing fractures which may occur without any preceding symptoms. An index of necrosis of 50 is proposed as a threshold for intervention, as it is a good discriminator between those that did and did not fracture, and had a positive predictive value of 77.8%. The only independent predictor of both pain and collapse was the extent of femoral head involvement.

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.