Aims. The localization of necrotic areas has been reported to impact the prognosis and treatment strategy for osteonecrosis of the femoral head (ONFH). Anteroposterior localization of the necrotic area after a femoral neck fracture (FNF) has not been properly investigated. We hypothesize that the change of the weight loading direction on the femoral head due to residual posterior tilt caused by malunited FNF may affect the location of ONFH. We investigate the relationship between the posterior tilt angle (PTA) and anteroposterior localization of osteonecrosis using lateral hip radiographs. Methods. Patients aged younger than 55 years diagnosed with ONFH after FNF were retrospectively reviewed. Overall, 65 hips (38 males and 27 females; mean age 32.6 years (SD 12.2)) met the inclusion criteria. Patients with stage 1 or 4 ONFH, as per the Association Research Circulation Osseous classification, were excluded. The ratios of anterior and posterior viable areas and necrotic areas of the femoral head to the articular surface were calculated by setting the femoral head centre as the reference point. The PTA was measured using Palm’s method. The association between the PTA and viable or necrotic areas of the femoral head was assessed using Spearman’s rank correlation analysis (median PTA 6.0° (interquartile range 3 to 11.5)). Results. We identified a negative correlation between PTA and anterior viable areas (rho −0.477; p = 0.001), and no correlation between PTA and necrotic (rho 0.229; p = 0.067) or posterior viable areas (rho 0.204; p = 0.132). Conclusion. Our results suggest that residual posterior tilt after FNF could affect the anteroposterior localization of necrosis. Cite this article: Bone Jt Open 2024;5(5):394–400

Objectives. Using a simple classification method, we aimed to estimate the collapse rate due to osteonecrosis of the femoral head (ONFH) in order to develop treatment guidelines for joint-preserving surgeries. Methods. We retrospectively analyzed 505 hips from 310 patients (141 men, 169 women; mean age 45.5 years . (sd. 14.9; 15 to 86)) diagnosed with ONFH and classified them using the Japanese Investigation Committee (JIC) classification. The JIC system includes four visualized types based on the location and size of osteonecrotic lesions on weightbearing surfaces (types A, B, C1, and C2) and the stage of ONFH. The collapse rate due to ONFH was calculated using Kaplan–Meier survival analysis, with radiological collapse/arthroplasty as endpoints. Results. Bilateral cases accounted for 390 hips, while unilateral cases accounted for 115. According to the JIC types, 21 hips were type A, 34 were type B, 173 were type C1, and 277 were type C2. At initial diagnosis, 238/505 hips (47.0%) had already collapsed. Further, the cumulative survival rate was analyzed in 212 precollapsed hips, and the two-year and five-year collapse rates were found to be 0% and 0%, 7.9% and 7.9%, 23.2% and 36.6%, and 57.8% and 84.8% for types A, B, C1, and C2, respectively. Conclusion. Type A ONFH needs no further treatment, but precollapse type C2 ONFH warrants immediate treatment with joint-preserving surgery. Considering the high collapse rate, our study results justify the importance of early diagnosis and intervention in asymptomatic patients with type C2 ONFH. Cite this article: Y. Kuroda, T. Tanaka, T. Miyagawa, T. Kawai, K. Goto, S. Tanaka, S. Matsuda, H. Akiyama. Classification of osteonecrosis of the femoral head: Who should have surgery?. Bone Joint Res 2019;8:451–458. DOI: 10.1302/2046-3758.810.BJR-2019-0022.R1

Aims. To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. Methods. We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors. Results. Osteoblasts from the intertrochanteric region of patients with ONFH showed lower alkaline phosphatase (ALP) activity and mineralization capacity than osteoblasts from the same skeletal site in age-matched patients with OA, as well as lower messenger RNA (mRNA) levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. In addition, osteoblasts from patients with ONFH secreted lower osteoprotegerin (OPG) levels than those from patients with OA, resulting in a higher receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ligand (RANKL)-to-OPG ratio. In patients with ONFH, osteoblasts from the femoral head showed reduced viability and mineralized nodule formation compared with osteoblasts from the intertrochanteric region. Notably, the secretion of the pro-resorptive factors interleukin-6 and prostaglandin E. 2. as well as the RANKL-to-OPG ratio were markedly higher in osteoblast cultures from the femoral head than in those from the intertrochanteric region. Conclusion. Idiopathic ONFH is associated with a reduced mineralization capacity of osteoblasts and increased secretion of pro-resorptive factors. Cite this article: Bone Joint Res 2021;10(9):619–628

Aims. Pain is the most frequent complaint associated with osteonecrosis of the femoral head (ONFH), but the factors contributing to such pain are poorly understood. This study explored diverse demographic, clinical, radiological, psychological, and neurophysiological factors for their potential contribution to pain in patients with ONFH. Methods. This cross-sectional study was carried out according to the “STrengthening the Reporting of OBservational studies in Epidemiology” statement. Data on 19 variables were collected at a single timepoint from 250 patients with ONFH who were treated at our medical centre between July and December 2023 using validated instruments or, in the case of hip pain, a numerical rating scale. Factors associated with pain severity were identified using hierarchical multifactor linear regression. Results. Regression identified the following characteristics as independently associated with higher pain score, after adjustment for potential confounders: Association Research Circulation Osseous classification stage IIIa or IIIb, bone marrow oedema, grade 3 joint effusion, as well as higher scores on pain catastrophizing, anxiety, and central sensitization. The final model explained 69.7% of observed variance in pain scores, of which clinical and radiological factors explained 37%, while psychological and neurophysiological factors explained 24% and demographic factors explained 8.7%. Conclusion. Multidimensional characteristics jointly contribute to the severity of pain associated with ONFH. These findings highlight the need to comprehensively identify potential contributors to pain, and to personalize management and treatment accordingly. Cite this article: Bone Joint Res 2024;13(11):673–681

Aims. The value of core decompression (CD) in the treatment of osteonecrosis of the femoral head (ONFH) remains controversial. We conducted a systematic review and meta-analysis to evaluate whether CD combined with other treatments could improve the clinical and radiological outcomes of ONFH patients compared with CD alone. Methods. We searched the PubMed, Embase, Web of Science, and Cochrane Library databases until June 2020. All randomized controlled trials (RCTs) and clinical controlled trials (CCTs) comparing CD alone and CD combined with other measures (CD + cell therapy, CD + bone grafting, CD + porous tantalum rod, etc.) for the treatment of ONFH were considered eligible for inclusion. The primary outcomes of interest were Harris Hip Score (HHS), ONFH stage progression, structural failure (collapse) of the femoral head, and conversion to total hip arthroplasty (THA). The pooled data were analyzed using Review Manager 5.3 software. Results. A total of 20 studies with 2,123 hips were included (CD alone = 768, CD combined with other treatments = 1,355). The combination of CD with other therapeutic interventions resulted in a higher HHS (mean difference (MD) = 6.46, 95% confidence interval (CI) = 2.10 to 10.83, p = 0.004) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score (MD = −10.92, 95% CI = -21.41 to -4.03, p = 0.040) and a lower visual analogue scale (VAS) score (MD = −0.99, 95% CI = -1.56 to -0.42, p < 0.001) than CD alone. For the rates of disease stage progression, 91 (20%) progressed in the intervention group compared to 146 (36%) in the control group (odds ratio (OR) = 0.32, 95% CI = 0.16 to 0.64, p = 0.001). In addition, the intervention group had a more significant advantage in delaying femoral head progression to the collapsed stage (OR = 0.32, 95% CI = 0.17 to 0.61, p < 0.001) and reducing the odds of conversion to THA (OR = 0.35, 95% CI = 0.23 to 0.55, p < 0.001) compared to the control group. There were no serious adverse events in either group. Subgroup analysis showed that the addition of cell therapy significantly improved clinical and radiological outcomes compared to CD alone, and this approach appeared to be more effective than other therapies, particularly in precollapse (stage I to II) ONFH patients. Conclusion. There was marked heterogeneity in the studies. There is a trend towards improved clinical outcomes with the addition of stem cell therapy to CD. Cite this article: Bone Joint Res 2021;10(7):445–458

Cite this article: Bone Joint Res 2023;12(1):5–8.

Aims. The effectiveness of total hip arthroplasty (THA) for patients with no or minimal radiological signs of osteoarthritis (OA) is unclear. In this study, we aimed to: 1) assess the outcome of such patients; 2) identify patient comorbidities and CT or MRI findings which predicted outcome; and 3) compare their outcome to the expected outcome of THA for hip OA. Methods. Adult patients undergoing THA for hip pain, with no or minimal radiological features of OA (Tönnis grading scale ≤ 1), were identified from a consecutive series of 1,925 THAs. Exclusion criteria were: inflammatory arthritis; osteonecrosis of the femoral head; prior trauma or infection; and patients without minimum one-year follow-up and patient-reported outcome measures (PROMs). The primary outcome measure was the Oxford Hip Score (OHS). Secondary outcome measures were EuroQol-visual analogue scale (EQ-VAS), University of California and Los Angeles (UCLA) scale, and patient satisfaction on a validated three-point ‘better’, ‘same’, or ‘worse’ scale. Results. A total of 107 patients with a median age of 41 years (IQR 18 to 73) were included, with mean follow-up of 6.0 years (SD 3.1). All patients underwent a diagnostic hip injection as a decision aid. Median postoperative OHS was 34 (IQR 28 to 42), with 36 patients (33%) achieving a patient-acceptable symptom state (OHS ≥ 42), lower than THA patients in international registries (40 to 43 points). Secondary outcomes were UCLA of 6 (4 to 8) and EQ-VAS of 73 (51 to 80); 91/102 patients (89%) felt ‘better’ and would ‘undergo surgery again'. Patients with chronic pain syndrome or hypermobility had lower OHS than patients without comorbidities (-6 points, p < 0.006). Overall, 84 patients had a CT and 34 patients an MRI. Patients with subchondral cysts (OHS 42 (37 to 45) vs 35 (26 to 36); p = 0.014) or joint space narrowing on CT (OHS 42 (IQR 37 to 44) vs 35 (26 to 36); p = 0.022) had higher function. Conclusion. Despite high satisfaction levels, patients undergoing THA with minimal or no radiological OA had lower postoperative function than typical THA patients. We recommend obtaining low-dose CT imaging and a diagnostic hip injection to aid decision-making. Cite this article: Bone Jt Open 2025;6(3):328–335

Aims. We compared the clinical outcomes of curved intertrochanteric varus osteotomy (CVO) with bone impaction grafting (BIG) with CVO alone for the treatment of osteonecrosis of the femoral head (ONFH). Methods. This retrospective comparative study included 81 patients with ONFH; 37 patients (40 hips) underwent CVO with BIG (BIG group) and 44 patients (47 hips) underwent CVO alone (CVO group). Patients in the BIG group were followed-up for a mean of 12.2 years (10.0 to 16.5). Patients in the CVO group were followed-up for a mean of 14.5 years (10.0 to 21.0). Assessment parameters included the Harris Hip Score (HHS), Oxford Hip Score (OHS), Japanese Orthopaedic Association Hip-Disease Evaluation Questionnaire (JHEQ), complication rates, and survival rates, with conversion to total hip arthroplasty (THA) and radiological failure as the endpoints. Results. There were no significant differences in preoperative and postoperative HHS or postoperative OHS and JHEQ between the BIG group and the CVO group. Complication rates were comparable between groups. Ten-year survival rates with conversion to THA and radiological failure as the endpoints were not significantly different between groups. Successful CVO (postoperative coverage ratio of more than one-third) exhibited better ten-year survival rates with radiological failure as the endpoint in the BIG group (91.4%) than in the CVO group (77.7%), but this difference was not significant (p = 0.079). Conclusion. Long-term outcomes of CVO with BIG were favourable when proper patient selection and accurate surgery are performed. However, this study did not show improvements in treatment results with the concomitant use of BIG. Cite this article: Bone Joint J 2021;103-B(4):665–671

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

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. 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. Method. A total of 18 patients with idiopathic ONFH undergoing THA in our institution were included. Trabecular bone explants were taken intraoperatively from the FH and the IT of patients. Bone microstructure was examined by micro-computed tomography (micro-CT). After bone sectioning, histological features were studied by hematoxylin and eosin staining. Differential gene expression was investigated using a microarray platform. Result. Micro-CT imaging showed higher trabecular separation and lower trabecular thickness and bone volume in trabecular bone from the FH than from the IT. Histological staining revealed that the number of osteoblasts on the bone surface and the percentage of empty lacunae were higher in trabecular bone from the FH. Transcriptome analysis identified a differential signature in trabecular bone from the FH compared to the IT. The gene ontology analyses of the genes overexpressed in trabecular bone from the FH revealed a range of enriched biological processes related to cell division and immune response. In contrast, most downregulated transcripts were involved in bone formation. Conclusion. This study identified changes in the microarchitecture, histological features and transcriptomic signature of trabecular bone from the FH of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition. This work was supported by PI22/00939 grant from ISCIII-FEDER-MICINN-AES and Luis Alvarez grant from IdiPAZ

Mesenchymal stem cells (MSC) have potent immunomodulatory and regenerative effects via soluble factors. One approach to improve stem cell-based therapies is encapsulation of MSC in hydrogels based on natural proteins such as collagen and fibrin, which play critical roles in bone healing. In this work, we comparatively studied the influence of collagen and fibrin hydrogels of varying stiffness on the paracrine interactions established by MSC with macrophages and osteoblasts. Type I collagen and fibrin hydrogels in a similar stiffness range loaded with MSC from donants were prepared by modifying the protein concentration. Viability and morphology of MSC in hydrogels as well as cell migration rate from the matrices were determined. Paracrine actions of MSC in hydrogels were evaluated in co-cultures with human macrophages from healthy blood donors or with osteoblasts from bone explants of patients with osteonecrosis of the femoral head. Lower matrix stiffness resulted in higher MSC viability and migration. Cell migration rate from collagen hydrogels was higher than from fibrin matrices. The secretion of the immunomodulatory factors interleukin-6 (IL-6) and prostaglandin E. 2. (PGE. 2. ) by MSC in both collagen and fibrin hydrogels increased with increasing matrix stiffness. Tumor necrosis factor-α (TNF-α) secretion by macrophages cultured on collagen hydrogels was lower than on fibrin matrices. Interestingly, higher collagen matrix stiffness resulted in lower secreted TNF-α while the trend was opposite on fibrin hydrogels. In all cases, TNF-α levels were lower when macrophages were cultured on hydrogels containing MSC than on empty gels, an effect partially mediated by PGE. 2. Finally, mineralization capacity of osteoblasts co-cultured with MSC in hydrogels increased with increasing matrix stiffness, although this effect was more notably for collagen hydrogels. Paracrine interactions established by MSC in hydrogels with macrophages and osteoblasts are regulated by matrix composition and stiffness

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. 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. Materials & Methods. Between November 1994 and December 2009, 187 revision hip arthoplasty were performed in 137 patients who had a diagnosis of osteonecrosis of the femoral head. Exclusion criteria included infection, recurrent instability, isolated polyethylene liner exchange, and inadequate follow-up (less than 3 years). The final study cohort of this retrospective review consisted of 72 patients (75 hips) with a mean age of 53.3 years (range, 34 to 76). Components used for the acetabular revision included a cementless porous-coated cup in 58 hips and an acetabular cage in 2 hips. Components used for the femoral revision included a fully grit-blasted tapered stem in 30 hips and a proximally porous-coated modular stem in 9 hips. The mean duration of follow-up was 7 years (range, 3 to 17). Results. Mean Harris hip score improved 49 points preoperatively to 90 points. At the time of final follow-up, 11 hips (14.7%) patients required additional reoperation procedure. Of these, six for aseptic loosening of acetabular cup and/or femoral stem, two for deep infection, one for recurrent dislocation, one for periprosthetic femoral fracture, and one for ceramic head fracture. Kaplan-Meier survivorship with an end point for cup revision for aseptic loosening was 98.4% at 5 years, 93.4% at 10 years, and with an end point for stem revision for aseptic loosening was 100% at 5 years, 97.4% at 10 years (Fig. 1). Conclusions. Unlike the previous report, our study showed lower failure rate of femoral stem after revision hip arthroplasty using modern cementless femoral components in patients with osteonecrosis of the femoral head. Aseptic cup loosening or osteolysis is the most common mechanism of failure at the medium-term follow-up following revision hip arthroplasty in these patients group

The rate of failure of primary THA in patients with osteonecrosis of the femoral head is higher than that in patients who undergo THA because of other diagnoses. We examined the results of cementless THA performed with second-generation in a consecutive series of young patients with osteonecrosis of the femoral head. Sixty-five consecutive primary THAs with insertion of a femoral stem with a circumferential proximal porous coating (HG Multilock prosthesis) and a cementless acetabular component (Harris-Galante II) were performed in 52 patients with osteonecrosis of the femoral head. These patients were followed prospectively and evaluated at a minimum of 10 years after surgery. Four patients (4 hips) died and three patients (3 hips) were lost to follow-up monitoring. The remaining 45 patients (58 hips) had a mean of 11.1 years (range, 10 to 13.4 years) of clinical and radiographic follow-up. One stem (1.7%) was revised because of aseptic loosening. Eighteen cups (31%) were revised because of excessive polyethylene wear and osteolysis. One hip (1.7%) underwent revision of both acetabular and femoral component because of excessive polyethylene wear and osteolysis. The mean Harrsi Hip Score improved from 49 points before surgery to 92.8 points after surgery in patients who did not undergo reoperation. Osteolysis around the acetabular component was present in 22 hips (37.9%). Femoral osteolysis was seen in 9 hips (15.5%), and there was no osteolysis below the lesser trochanter in any hip. Circumferentially porous-coated second-generation femoral prostheses provide excellent fixation in young patients with osteonecrosis of the femoral head. However, a high rate of polyethylene wear and osteolysis in these high-risk patients remains a challenging problem

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. The purpose of this study was to evaluate the functional and radiographical mid-term follow-up results of a second generation metal-on-metal cementless total hip arthroplasty for the treatment of osteonecrosis of the femoral head in patients younger than 50 years. Methods. Twenty eight patients (35 hips) who underwent total hip arthroplasty with second generation metal-on-metal bearings for osteonecrosis of the femoral head at a minimum 5-year follow-up were included in this study. There were 5 women (6 hips) and 23 men (29 hips) who had a mean age of 40 years (range, 23 to 49 years) and a mean follow-up of 7 years. We used a Fitmore (Zimmer) cup and a 28mm Metasul femoral head in all cases. A CLS (Protek AG/Zimmer) femoral stem was used in 30 hips and a Cone prosthesis¯ (Protek AG) was used in 5 hips. Functional results were measured by Harris hip (HHS) and WOMAC scores. Radiographic evaluations were used to assess loosening and osteolysis according to Gruen and Delee and Charnley criteria. Results. The mean Harris hip score improved from 58 points (range, 35 to 67 points) pre-operatively to 92 points (range, 84 to 99 points) post-operatively, and the mean WOMAC score improved from 73 points (range, 63 to 89 points) to 30 points (range, 24 to 41 points). On radiological evaluation, all femoral and acetabular components were well-fixed without loosening or subsidence. Osteolysis was observed in 5 hips (14%) (acetabular osteolysis in 2 cases-Zone 2; 1, Zone 3; 1, femoral osteolysis in 3 cases- Zone 1; 2, Zone 7; 1). There were no complications including immediate post-operative deep infection, delayed infection, or recurrent dislocation. There was no case of revision for aseptic loosening. Conclusion. Second generation metal-on-metal cementless total hip arthroplasty for the treatment of osteonecrosis of the femoral head in patients younger than 50 years showed favorable functional and radiographic results

Introduction. The purpose of this study was to evaluate the functional and radiographical results in patients younger than 30 years who underwent cementless third generation ceramic-on-ceramic total hip arthroplasty for osteonecrosis of the femoral head. Methods. Forty one patients (55 hips) who underwent total hip arthroplasty with third generation ceramic-on-ceramic bearings for osteonecrosis of the femoral head with a minimum 4-year follow-up were included in this study. There were 26 men and 15 women who had a mean age of 26 years (range, 16 to 29 years). The average duration of follow-up was 6 years (range, 4 to 7 years). All surgeries were done by a single hip surgeon and third generation ceramic-on-ceramic articulations were used. Securefit (Stryker) acetabular components were used in 46 hips and Duraloc (Depuy) in 9 hips. Accolade (Stryker) femoral stems were used in 33 hips, cone prosthesis (Zimmer) in 18 hips and CLS (Zimmer) in 4 hips. Functional results were measured by Harris hip (HHS) and WOMAC scores. Radiographic evaluation was assessed for loosening and osteolysis according to Gruen and Delee and Charnley criteria. Results. The average HHS improved from 53 points (range, 24 to 59 points) pre-operatively to 95 points (range, 88 to 100 points) at last follow-up. WOMAC scores improved from 72 points (range, 50 to 98 points) to 25 points (range, 21 to 37 points). Thirty nine patients (51 hips) continued their normal occupation. There was no aseptic loosening, osteolysis, and no prosthesis had been revised. There was one patient who complained of continuous squeaking and two patients with Brooker grade I heterotopic ossification. There were no other major complications such as ceramic fracture. Conclusion. Total hip arthroplasty with third generation ceramic-on-ceramic bearings for osteonecrosis of the femoral head especially in active and young patients resulted in satisfactory clinical and radiological results at minimum 4 year follow-up. If long-term follow-up shows excellent results, then the age limit for total hip arthroplasty might be lowered