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

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

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

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

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.

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: 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

Introduction

The most frequent diagnosis in young adults undergoing total hip arthroplasty (THA) is osteonecrosis of the femoral head (ONFH), an evolving and disabling condition with an increasing prevalence worldwide. Treatment of ONFH remains a challenge mainly because of a lack of understanding of the disease's pathophysiological basis. This study investigated the biological processes that could be affected by ONFH by comparing the microstructure, histological characteristics and transcriptomic profile of trabecular bone from the femoral head (FH) and the intertrochanteric region (IT) of patients suffering from this condition.

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

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: 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

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.

Bone marrow stem cells (BMSCs) represent a collection of different cell types exhibiting stem cell characteristics but with notable heterogeneity. Among these, Skeletal Stem Cells (SSCs) represent a distinct matrix subgroup within BMSC and demonstrate a specialized capacity to facilitate bone formation, recruit chondrocytes, and contribute to hematopoiesis. SSCs play a pivotal role in orchestrating the functions of skeletal organs. Local ischemia has a significant impact on cell survival and function. We hypothesize that bone ischemia induces alterations in the differentiation potential of SSCs, consequently influencing changes in bone structure.

We mechanically dissected tissue from the necrotic segment in the femoral head and more normal appearing areas from the femoral neck of specimens from 5 patients diagnosed with osteonecrosis of the femoral head (ONFH). These tissues were enzymatically broken down into individual cell suspensions. Utilizing fluorescence-activated cell sorting (FACS) based on specific surface markers indicative of human skeletal stem cells (hSSC), namely CD45- CD235a- CD31- TIE2- Podoplanin (PDPN)+ CD146- CD73+ CD164+, we isolated a distinct cell population. Subsequent in vitro evaluations, focusing on clonogenicity, osteogenesis, and chondrogenesis were conducted to assess the functional prowess of these SSCs. Moreover, we introduced BMP2 at a concentration of 50ng/ml to SSCs extracted from necrotic regions to potentially reinstate their osteogenic capabilities.

We effectively isolated SSCs from both Necrotic and Non-necrotic Zones. We observed an augmented clonal formation capacity and chondrogenesis ability of SSCs isolated from the necrotic region, accompanied by a significant decline in osteogenic ability (P＜0.01), an effect not reversible even with the addition of BMP2.

Ischemia adversely affects the proliferation and function of SSCs, resulting in a diminished osteogenic capacity and an insensitivity to BMP2, ultimately leading to structural alterations in bone tissue.

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

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.