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 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 (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 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

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

Osteonecrosis is a pathologic bone condition caused by a disruption in the osseous circulation and impairment of normal cellular function which ultimately leads to bone infarction, osteocyte death, and joint degeneration. The incidence of osteonecrosis in the general population has been reported to be approximately 3 per 100,000 people. Up to 20,000 new cases are diagnosed each year and this condition is the indication for surgery in approximately 10% of all total hip arthroplasties performed in the United States. The hip is the most common joint affected, with approximately 75% of cases occurring in this joint, although multifocal osteonecrosis (defined as involvement of more than 3 joints) can also occur. Other commonly observed locations for osteonecrotic lesions include the knee, shoulder, wrist, and ankle. Joint preserving procedures may be performed for early stages without evidence of collapse, while intermediate lesions (e.g. femoral head collapse < 2 mm) may be candidates for joint preserving procedures such as bone grafting and rotational or proximal femoral varus osteotomies. However, total hip arthroplasty is usually required in advanced cases where there are large lesions, deformation of the femoral head, or acetabular involvement. Osteonecrosis has been traditionally associated with poor outcomes following total hip arthroplasty. However, recent studies using newer implant designs and surgical techniques have demonstrated outcomes comparable to the general total hip arthroplasty population. Johansson and colleagues, in a systematic reviewed of the literature, observed a decrease in the revision rate from 17% to 3% for arthroplasties performed later than 1990. The clinical outcomes were also comparable between patients who had osteoarthritis and those who had osteonecrosis. The young age at which these patients often present makes bearing surface choice challenging. Bearings that have low liner wear rates, such as ceramic bearings, had concerns with implant durability following reports of chipping and fracture of the ceramic. However, recent studies evaluating ceramic bearings in young patients with osteonecrosis have demonstrated that newer third and fourth generation ceramics have solved many of these issues. Byun et al. evaluated the clinical outcomes of ceramic bearings in patients younger than 30 years who had osteonecrosis and observed that at six year follow-up, none of the bearings had failed and that 95% of patients were able to continue with their prior occupation. Similar results at even longer follow-up periods were reported by Kim and colleagues who observed no failures in 93 ceramic hips at a mean follow-up of 11 years. Polyethylene wear continues to be a concern for these younger, more active patients. Early studies with non-highly cross linked polyethylene demonstrated high wear rates in these patients. Although newer polyethylene designs have become available which have demonstrated substantially lower wear than the traditional ultra high molecular weight polyethylene cups of the recent past, further studies are needed with these newer polyethylene bearings in the osteonecrosis population. The goal of treatment for femoral head osteonecrosis remains early diagnosis and joint preservation. For patients who present with femoral head collapse or acetabular involvement, total hip arthroplasty often is the only treatment option left. Although clinical outcomes for these patients were initially poor in earlier reports, the advent of modern cementless arthroplasty components, refined surgical techniques, and newer bearing designs have greatly improved the outcomes of this procedure

Osteonecrosis (ON) is a debilitating condition that can progress to severe arthritis of the hip. While its exact pathogenesis remains poorly understood, ON is known to be associated with risk factors such as corticosteroid use, alcoholism, and autoimmune disease. Initial radiographic evaluation can reveal sclerotic and cystic changes in the femoral head, which are usually the first clues in diagnosis. Despite these indicators, plain radiographs generally are not sufficient for diagnosis, therefore requiring subsequent magnetic resonance imaging (MRI) studies. Moreover, performing an appropriate assessment of these imaging modalities can help guide the course of treatment. Treatment options are aimed at slowing or stopping the onset of femoral head collapse and include non-operative management, joint preservation procedures, and total joint arthroplasty. Patients at risk of developing ON may benefit from early diagnosis because the characteristic small or medium-sized pre-collapse lesions that are associated with this stage can often be treated with a non-operative or joint preservation approach. However, patients typically present with advanced disease progression and sometimes an unsalvageable joint, thereby necessitating more invasive operative intervention. Surgical modalities include the use of osteotomy, core decompression, vascular grafts, bone graft substitutes, resurfacing, and finally, total hip arthroplasty. Additionally, reports from the past several decades describe improved outcomes and survivorship of these surgical treatment options. Therefore, our purpose is to highlight recent evidence regarding the management of ON with emphasis on the various forms of operative intervention as well as their outcomes

Osteonecrosis of the femoral head (ONFH) is a debilitating, painful, progressive, and refractory disease that has multiple etiologic risk factors. It is caused by bone cell death, which itself has various causes, leading to femoral head collapse and subsequent osteoarthritis. ONFH primarily influences patients aged from 20 to 50 years; in addition, bilateral hip joints are involved in 75% of patients. Causes include use of corticosteroids, alcohol abuse, previous trauma, hemoglobinopathy, Gaucher disease, coagulopathies, and other diseases. No pharmacologic treatment has been shown to be effective for early ONFH. Outcomes of total hip arthroplasty (THA) for these young and active patients have some drawbacks, primarily due to the young age of these patients, limited lifetime and durability of the implants and their fixation, and the skeletal manifestations of osteonecrosis. As a result of these concerns, there has been an increased focus on early interventions for ONFH aimed at preservation of the native articulation. Core decompression is currently the most widely accepted surgical treatment at the early stage of avascular osteonecrosis (AVN); however, due to limited efficacy, its use has been debated. There is currently no standardised protocol for evaluating and treating osteonecrosis of the femoral head in adults in the United States. Although total hip replacement is the most frequent intervention for treatment of post-collapse (Steinberg stage-IIIB, IVB, V, and VI) osteonecrosis; core decompression is the most commonly offered intervention for symptomatic, pre-collapse (Steinberg stage-IB and IIB) osteonecrosis. Less frequently offered treatments include non-operative, pharmacologic or modality management, osteotomy, vascularised and non-vascularised bone-grafting, hemiarthroplasty, resurfacing and arthrodesis. A promising, minimally invasive, core decompression procedure combined with a mesenchymal stem cell grafting technique which restores vascularity and heals osteonecrotic lesions has become popularised. This procedure is called a bone marrow aspirate concentrate (BMAC) procedure. During a BMAC, mesenchymal stem cells (in the form of concentrated iliac crest bone marrow) are injected through a core decompression tract into the area of necrosis in the femoral head. Most patients with early (pre-collapse) disease have excellent results at 2 to 5 years of clinical follow-up. Patients are weight bearing as tolerated on crutches after the procedure for 6 weeks, and are able to go home on the same day or next day after surgery with minimal pain. We can report on the early, promising results of 300 patients with ONFH treated with BMAC in the United States by two expert hip surgeons with at least 75%-80% survivorship. The care of adults with osteonecrosis of the femoral head is highly variable. This paper will discuss the various non-operative and operative treatment algorithms for ONFH available today. We will also report on a promising, new technique (BMAC), which improves the efficacy of traditional core decompression for early ONFH. The goal of treatment of early ONFH is to avoid THA in young, active patients and this talk will discuss those interventions and treatments which help accomplish that goal

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.

Background: Traditionally, it is believed that structural failure of the ischemic epiphysis as well as changes in radiodensity seen in Legg-Calve-Perthes disease are due to repair. Little is known if bone material properties are altered following ischemic necrosis of the juvenile femoral head. Purpose of this study was to determine bone matrix mineralization density, an important determinant of bone quality and strength, in an experimental model of juvenile ischemic osteonecrosis. Methods: Ten piglets were surgically induced with ischemic osteonecrosis and euthanized at 4- and 8 weeks following surgery. Contralateral, unoperated femoral heads were used as controls. Bone Mineralization Density Distribution (BMDD) parameters were determined using quanitative backscattered electron imaging (qBEI) in the epiphyseal calcified cartilage, subchondral and central trabecular bone region. Histological assessment was also performed. Results: In necrotic calcified epiphyseal cartilage matrix as well as subchondral bone matrix, a significant increase in the degree (CaMean, Ca Peak) as well as the homogeneity of mineralization (CaWidth reduction) and a significantly reduced amount of low mineralized matrix (CaLow) were observed at 4 and 8 weeks post ischemia induction. In the necrotic central trabecular region a significant increase in the degree and homogeneity of mineralization, as well as a decrease in the amount of low mineralized bone was found at 8 weeks post-ischemia induction, but not at 4-weeks, indicating that changes in necrotic trabecular bone occur more slowly. Changes in the necrotic calcified cartilage region were more dramatic than in necrotic bone. Discussion: Our findings indicate that the mineralization process continues in the necrotic calcified cartilage and bone following femoral head infarction. This leads to an increased degree and homogeneity of mineralization in calcified cartilage and bone matrices and therefore altered material properties. These alterations in matrix mineralization status would lead to more brittle bone, prone to micro-fractures and may partly explain the weakening of structural properties of necrotic bone. Moreover, an increase in calcified cartilage and bone mineralization may also explain the increased radiodensity seen in the early stage of Perthes disease prior to repair and/or structural failure

Introduction: Osteonecrosis (ON) is a disabling disease, which often affects young adults after corticosteroid immunosuppression for organ transplantation. Reducing risk factors remains the only preventive measure for this condition. Our goal was to determine if diabetes has any influence in developing ON after kidney transplantation. Materials and Methods: We identified 2881 renal transplantation patients with the following inclusion criteria: age > 16 years, no history of corticosteroid exposure. There were 1762 (61%) diabetics and 1119 (39%) non-diabetics. Mean age was 43 years (range, 16 to 77) and mean follow-up was 128 months (range, 36 to 242). Osteonecrosis free survivorship was defined as time from transplant to diagnosis of ON. Results: Kaplan-Meier life table analysis at 5 years revealed that the incidence of ON was 4% for diabetics vs. 9% for non-diabetics (ON- free survivorship 96%, [95% confidence interval 0.952 to 0.970] vs. 91% [95% C.I. 0.896 to 0.929], respectively [p < 0.0001]). At 10 years, the ON incidence was 5% for diabetics vs. 10% for non-diabetics representing a 50% reduction. Diabetes was the strongest independently predictive factor for ON-free survival (relative risk 0.47, p< 0.0001), while other factors were also independently significant but had a weaker relationship; (rejection episodes [RR 1.17, p=0.009], year of transplantation [RR 0.96, p=0.01]). Discussion: Although the most common reason for renal transplantation, in adults, is diabetic nephropathy (61%), only a small fraction actually developed ON as compared to the non-diabetic population. The reason for this is unknown but might be related to lipid metabolism, high glucose levels, or neovascularization analogous to diabetic retinopathy. Presence of diabetes is associated with a dramatic risk reduction in developing ON. The magnitude of the risk reduction was greatest for diabetes as compared to all other risk factors analyzed

Introduction. The mechanism for development of corticosteroid-induced osteonecrosis of the femoral head remains to be understood. Elucidation of the mechanism and the establishment of preventive methods have been critical issues. To establish a clinical method for prevention of corticosteroid-induced osteonecrosis, we have examined the suppressive effect of reduced glutathione (GSH) in a corticosteroid-induced rabbit model. Methods. Female Japanese white rabbits were separated into five groups: Group S4, a single intramuscular 4 mg/kg methyl prednisolone acetate (MPSL) administration in the gluteus; Group G4, administration of a 5 mg/kg regular dose GSH for 5 consecutive days starting on the day of a single 4 mg/kg MPSL administration; Group S20, a single intramuscular administration of 20 mg/kg MPSL in the gluteus; Group G20, administrations of 5 mg/kg GSH for 5 consecutive days starting on the day of a single 20 mg/kg MPSL administration; and Group N, control group with no treatment. All rabbits were sacrificed 14 days after MPSL administration. Histopathological analyses were performed by hematoxylin-eosin staining. Immunohistological analyses were performed using anti-lectinlike oxidized LDL reseptor-1 antibody (anti-LOX-1 antibody). Results. Osteonecrosis occurred in 70% of the animals in Group S4, whereas, no osteonecrosis was observed in Group G4, showing a significant suppression. Osteonecrosis was observed in 90% of the animals in Group S20, and it was significantly suppressed in Group G20, with only 30% of the animals affected. The expression of LOX-1 was significantly elevated in Groups S4 and S20. In Group N, no osteonecrosis was observed in all cases, while the expression of LOX-1 was only marginally detected. Conclusion. Abnormal expression of LOX-1 which was examined in the present study is used as an indicator of tissue hyperoxidation. GSH is known to be an enzyme which protect tissues and the vascular endothelium. In the present study, significant suppression of osteonecrosis was observed in Groups G4 and G20 which received GSH administrations, in which osteonecrosis occurred in 0 and 30%, respectively. In addition, LOX-1 expression was also reduced. These results showed that GSH at the regular dose suppressed oxidative stress and development of osteonecrosis, suggesting an effective clinical application of GSH

Introduction. Osteonecrosis of the knee encompasses three conditions; spontaneous osteonecrosis of the knee, secondary osteonecrosis (ON) and post-arthroscopic ON. Early stage lesions can be managed by non-operative measures that include protected weight-bearing and analgesia. The aim of this study was to report the experience of the authors in managing early stages of knee ON by analysing the functional outcome and need for surgical intervention. Methods. All patients treated for osteonecrosis of the knee between 1st August 2001 and 1st April 2014 were prospectively collected. Treatment consisted of touch-down weight bearing for four to six weeks. The cases were retrospectively reviewed. MR imaging was evaluated for the stage of disease according to Koshino's Classification system, the condyles involved and the time taken for resolution. Tegner Activity Scale, VAS pain, Lysholm, WOMAC and IKDC scores were recorded at presentation and final follow up. Results. 51 cases were treated for knee ON at our centre; 40 cases of SONK, seven secondary ON and four post-arthroscopic ON. Of the seven cases of secondary osteonecrosis; 5 were secondary to self-reported high ethanol intake and two secondary to corticosteroid treatment. The mean age of the group was 56.9 years and 68.7% were male. The medial femoral condyle was the most commonly affected (54.9%). 86% reported resolution of clinical symptoms and a statistically significant improvement was reported in all functional outcome measures. Four patients required total knee arthroplasty; three in the post-arthroscopic group within 15 months and one following ON secondary to corticosteroids performed at 5 months. Conclusion. Early stage spontaneous osteonecrosis of the knee can be managed successfully without surgery if diagnosed early. Although secondary and post-arthroscopic ON seem to be more resistant. Larger studies are required to confirm or refute this. Level of Evidence. IV – a case series. Conflict of Interests. The authors confirm that they have no relevant financial disclosures or conflicts of interest. Ethical approval was not sought as this was a systematic review

Osteonecrosis is a potentially devastating condition with poorly defined pathogenesis that can affect several anatomical areas with or without a previous traumatic insult. Post traumatic osteonecrosis (PON) in the foot and ankle has been commonly described in the talus and navicular but rarely in the distal tibia. PON of the distal tibia is a rarely reported and infrequent complication of fracture dislocations of the ankle. Its scarcity can lead to misdiagnosis and inappropriate management due to a lack of clinical knowledge or suspicion with resultant severe functional compromise. We aim to highlight the clinical and radiological features of PON of the distal tibia and report the findings in a series of four patients following a fracture dislocation of the ankle. Three patients sustained a SER4 fracture dislocation and one patient sustained a PER4 fracture dislocation in keeping with standard patterns of injury seen in most trauma units. In each case, PON of the distal tibia presented with progressive anterolateral tibial plafond collapse and valgus deformity of the ankle. The radiological features previously reported in the literature are based on plain film x-ray, CT and MRI but no description of SPECT-CT findings. One of the patients in the series underwent SPECT-CT following clinical suspicion of PON and thus we describe the findings not previously reported. Our objective is to highlight this rare condition as a potential cause for ongoing pain following fracture dislocation of the ankle as well as advocating the use of SPECT/CT as a useful imaging modality to aid in the diagnosis

Abstract

Introduction: Osteonecrosis continues to be a challenging problem in orthopaedic practice. Etiology is multi-factorial but steroid- and alcohol-associated osteonecrosis contributed to more than two thirds of all the cases. While the pathogenesis of the disease is still unknown, many new insights have emerged from research in the last decade. Studies have demonstrated that both steroids and alcohol promote adipogenesis and inhibit osteogenesis, in vitro and in vivo, leading to osteonecrosis and osteoporosis. It has been found that Dexamethasone can turn on adipogenic transcription factor PPARy2 but suppress osteogenic transcription factor Cbfa1/Runx2. Steroids also decrease VEGF production resulting in inhibition of angiogenesis by osteoprogenitor cells. However, alcohol produces adipogenesis through a different mechanism at a point downstream in the fatty acid metabolism pathway, but it does inhibit osteogenesis by decreasing osteocalcin gene expression. Increased adipogenesis and osteoporosis, together with decreased osteogenesis and angiogenesis, will eventually lead to the final pathway of osteonecrosis

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

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

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

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

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

Introduction. Osteonecrosis (ON) is a bone disease characterized by death of osteocytes and loss of associated hematopoietic elements usually occurring as focal lesions in weight bearing joints such as the hip. The pathophysiology of the disease is still unclear and osteonecrosis can be viewed as both a vascular and a bone disease. The number of mesenchymal stem cells (precursors of osteoblastic cells) has been shown to be depressed in patients with osteonecrosis. Also, the proliferation rate of the osteoblastic cells in the proximal femur may be depressed. These findings raised the possibility that osteonecrosis might be a disease of bone cells or bone metabolism. On this basis, we started this study to evaluate bone metabolism status among patients with osteonecrosis. Methods. In a prospective study, we evaluated 110 patients with osteonecrosis at the time of the diagnosis for vitamin D, parathormone, osteocalcin, and c-telopeptide measurements. DEXA was performed in all patients as well. We excluded from this study patients with sickle cell anemia (n=5), Gaucher disease (n=1), on hemodialysis (n=14), and who were already treated for osteoporosis (n=8). Results. There were 20 women and 90 men (mean age 47 ± 11 years). Twenty percent of the patients had unilateral osteonecrosis of the femoral head, 61 % of the patients had bilateral osteonecrosis, and 20 % had multifocal disease. Risk factors were corticosteroid and alcohol abuse. Vitamin D deficiency (<15 ng/ml) was found in 60 % of the patients and vitamin D insufficiency (15 to 30 ng/ml) was found in 15% of the patients. Secondary hyperparathyroidism (>55pg/ml) was present in only 7 patients. Patients with alcohol abuse had significantly lower vitamin D concentration than the other patients: 11.9 ± 8.7 vs. 20.8 ± 9.2 ng/ml (p=0.005). Among 90 samples, 45 showed an osteocalcin level below the normal range (<14 ng/ml). Most of the patients had a normal level of C-telopeptide. Patients with corticosteroid-associated osteonecrosis had significantly lower osteocalcin levels than others osteonecrotic patients: 14.1 ± 5.3 vs 22.7 ± 13.0 ng/ml (p=0.015). Bone mineral density measurements were obtained for 60 patients and showed a T-score < -1.5 at the lumbar site and < 1.8 at the hip. Conclusion. Patients with osteonecrosis have a high prevalence of vitamin D deficiency without secondary hyperparathyroidism. They also display a low bone turnover confirmed by low osteocalcin levels and normal levels of C-telopeptide. Osteonecrosis is also associated with severe osteopenia

Purpose. To determine (i) the relationship between osteonecrosis and hip function, physical function and quality of life in adolescents and young adults treated for DDH; and (ii) how affected children change over 10 years. Methods. We included 109 patients (mean age 19.2 ± 3.8 years) with osteonecrosis and 30 age-matched patients without osteonecrosis following DDH treatment between 1992–2005. All completed valid patient-reported outcome measures to quantify their hip function (maximum score 100); physical function (maximum score 100); and quality of life (maximum score 1). Of these, 39 patients had been followed prospectively since 2006, allowing quantification of within-person changes over time. We graded all radiographs for severity of osteonecrosis, residual dysplasia, subluxation and osteoarthritis. We determined the association between patient-reported outcomes and radiographic severity of osteonecrosis using mixed-effects regression analysis; and repeated-measures analysis of variance to quantify person changes over time. We adjusted for age, prior operations and acetabular dysplasia. Results. In 135 patients (168 hips) with and without osteonecrosis, mean differences (95% confidence interval) in hip function, physical function and quality of life were 0.75 (−6.67, 8.17), −1.97 (−17.58, 13.60) and −0.05 (−0.91, 0.36), respectively. Adjusted analysis showed no difference in these outcomes based on radiographic severity of osteonecrosis (p> 0.05). Of 39 patients followed over 10 years, 4 had undergone hip arthroplasty. For the remainder, mean changes (95% confidence interval) in hip function, physical function and quality of life from baseline to current assessment were 7.18 (−2.11, 12.26), −2.11 (−15.47, 11.25), −0.03 (−0.11, 0.05), respectively. Radiographic severity of osteonecrosis was not correlated with changes in patient-reported outcomes over time. Conclusion. Osteonecrosis secondary to DDH remains relatively benign even in young adulthood. Overall, patients demonstrated good hip function, physical function and normal quality of life. Equally, children maintained such high levels over the course of 10 years if their hip survived

Introduction. Osteonecrosis of the femoral head is a devastating disease in young patients and remains a challenge for clinicians and researchers alike. To increase understanding of the disease and produce effective treatments that preserve a patient's native hip, an animal model that mimics the disease process in humans, including collapse of the femoral head, is essential. Our goal was to create such a bipedal model by surgically inducing osteonecrosis in the femoral heads of chickens. Methods. A lateral approach to the proximal femur was used to access the hip, dislocate the femoral head, and sever the periosteal network of blood vessels. At 4, 8, 12, and 20 weeks after surgery, both the left (experimental) and right (control) femoral heads were harvested from 6 chickens for micro-CT and histological analysis. Results. Hematoxylin and eosin stained sections beginning at 4 weeks demonstrated trabecular bone loss, empty osteocyte lacunae, and new bone formation on existing trabeculae. By 20 weeks, subchondral cyst formation and femoral head collapse was observed. Micro-CT analysis of the operative hips compared to matched controls showed decreased bone volume (18% at 4 weeks, 36% at 8 weeks, 45% at 12 weeks), increased porosity (2.1%, 7.3%, 10.7%), and increased average pore diameter (13%, 18%, 37%). Conclusion. The results indicate that operative disruption of blood supply to the femoral head produces changes consistent with osteonecrosis, including progression to collapse, as seen in human end-stage disease. A successful osteonecrosis model provides the basis to test new therapies, such as bone graft substitutes seeded with stem cells and growth factors