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 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

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. 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

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

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

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

Objectives. An experimental piglet model induces avascular necrosis (AVN) and deformation of the femoral head but its secondary effects on the developing acetabulum have not been studied. The aim of this study was to assess the development of secondary acetabular deformation following femoral head ischemia. Methods. Intracapsular circumferential ligation at the base of the femoral neck and sectioning of the ligamentum teres were performed in three week old piglets. MRI was then used for qualitative and quantitative studies of the acetabula in operated and non-operated hips in eight piglets from 48 hours to eight weeks post-surgery. Specimen photographs and histological sections of the acetabula were done at the end of the study. . Results. The operated-side acetabula were wider, shallower and misshapen, with flattened labral edges. At eight weeks, increased acetabular cartilage thickness characterised the operated sides compared with non-operated sides (p < 0.001, ANOVA). The mean acetabular width on the operated side was increased (p = 0.015) while acetabular depth was decreased anteriorly (p = 0.007) and posteriorly (p = 0.44). The cartilage was thicker, with delayed acetabular bone formation, and showed increased vascularisation with fibrosis laterally and focal degenerative changes involving chondrocyte hypocellularity, chondrocyte cloning, peripheral pannus formation and surface fibrillation. . Conclusions. We demonstrate that femoral head AVN in the young growing piglet also induced, and was coupled with, secondary malformation in acetabular shape affecting both articular and adjacent pelvic cartilage structure, and acetabular bone. The femoral head model inducing AVN can also be applied to studies of acetabular maldevelopment, which is less well understood in terms of developing hip malformation. Cite this article: Bone Joint Res 2014;3:130–8

Introduction. Osteonecrosis (ON) is one of the most debilitating skeletal disorders. Most patients with ON of the femoral head eventually require surgery, usually total hip arthroplasty, within a few years of disease onset. Previous reports have shown that alendronate reduces osteoclastic activity and reduces the incidence of femoral head collapse in osteonecrotic hips. A randomized study to examine the ability of alendronate to delay or prevent femoral head collapse was performed. Methods. From June 2005 to December 2006, sixty four patients were enrolled and randomly assigned to alendronate or placebo. Five patients were excluded from the analysis because of their failure to adhere to the study protocol. Disease progression was evaluated using radiographs and magnetic resonance imaging (MRI). Results. While the proportion of patients in the alendronate group who underwent total hip arthroplasty was 13% (4 of 31 patients), the proportion of patients undergoing the procedure in the placebo group was 29% (8 of 28 patients; p=0.22, cumulative incidence between the two groups by log-rank test). As such, there was a numerical reduction in the rate of total hip arthroplasty in the alendronate group compared to placebo that did not achieve statistical significance likely because the study was originally powered to detect a between-group difference based on event rates of 35.7% and 3.4% in the placebo and alendronate groups, respectively. Conclusion. Alendronate treatment shows promise for the treatment of atraumatic osteonecrosis. However, additional studies are needed to confirm our results. Osteotomy or bone grafting still remains the procedure of choice for osteonecrosis of the femoral head prior to collapse. Disclosure. The study was supported in part by Merck Sharp & Dohme (I.A) Corp. Taiwan Branch. All these schools received some financial reimbursement for the study

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 (ON) is a disease that ultimately results in bone collapse. We investigated the correlation between SNPs and osteonecrosis. Methods. In this study, 109 patients with systematic lupus erythematosus (SLE) (21 with and 88 without osteonecrosis) were collected for genotype analysis of 7 genes including VEGF, MTHFR, eNOS, and PAI-1 related to the blood system and BMP2 and PPARγ-2, genes that regulate the differentiation of bone marrow stromal cells. Results. The result of the combined analysis of the susceptible BMP2 (rs3178250) TC genotype, MTHFR (rs1801133) CC genotype and VEGF (rs833069) AA genotype was OR: 0.185, 95 % CI:0.044 - 0.774 (p=0.021). In addition, when the different genotype combinations were analyzed the result for BMP2 (rs3178250) TC, MTHFR (rs1801133)CC, and PPARγ-2 (rs11128596) AA genotype was OR:0.096, 95 % CI:0.044-0.774 (p=0.012); the result for BMP2(rs3178250) TT, VEGF (rs833069) AG, and PPARγ-2 (rs11128596) CA genotype was OR:0.099, 95 % CI:0.016-0.597 (p=0.012); and that of VEGF AA, eNOS 298T GT, and eNOS 27bp tandem repeat 5R5R genotype was OR:0.060, 95 % CI:0.006- 0.588 (p =0.016), respectively. Conclusion. The results of this research provides an important reference to predict corticosteroid-associated osteonecrosis for SLE patients, providing related genotypic molecular epidemiology and possible discussion on mechanisms of pathogenicity for corticosteroid-associated osteonecrosis in SLE patients in Taiwan. The result of this research not only serves as a reference for possible ON risk factors in SLE patients with chronic corticosteroid use, but also forms a basis for treatment and medication in the clinical setting

Results in patients undergoing total hip arthroplasty (THA) for femoral head osteonecrosis (ON) when compared with primary osteoarthritis (OA) are controversial. Different factors like age, THA type or surgical technique may affect outcome. We hypothesized that patients with ON had an increased revision rate compared with OA. We analysed clinical outcome, estimated the survival rate for revision surgery, and their possible risk factors, in two groups of patients.

In this retrospective cohort analysis of our prospective database, we assessed 2464 primary THAs implanted between 1989 and 2017. Patients with OA were included in group 1, 2090 hips; and patients with ON in group 2, 374 hips. In group 2 there were more men (p<0.001), patients younger than 60 years old (p<0.001) and with greater physical activity (p<0.001). Patients with lumbar OA (p<0.001) and a radiological acetabular shape type B according to Dorr (p<0.001) were more frequent in group 1. Clinical outcome was assessed according to the Harris Hip Score and radiological analysis included postoperative acetabular and femoral component position and hip reconstruction. Kaplan-Meier survivorship analysis was used to estimate the cumulative probability of not having revision surgery for different reasons. Univariate and multivariate Cox regression models were used to assess risk factors for revision surgery.

Clinical improvement was better in the ON at all intervals. There were 90 hips revised, 68 due to loosening or wear, 52 (2.5%) in group 1, and 16 (4.3%) in group 2. Overall, the survival rate for revision surgery for any cause at 22 years was 88.0 % (95% CI, 82-94) in group 1 and 84.1% (95% CI, 69 – 99) in group 2 (p=0.019). Multivariate regression analysis showed that hips with conventional polyethylene (PE), compared with highly-cross linked PEs or ceramic-on-ceramic bearings, (p=0.01, Hazard Ratio (HR): 2.12, 95% CI 1.15-3.92), and cups outside the Lewinnek´s safe zone had a higher risk for revision surgery (p<0.001, HR: 2.57, 95% CI 1.69-3.91).

Modern highly-cross linked PEs and ceramic-on-ceramic bearings use, and a proper surgical technique improved revision rate in patients undergoing THA due to ON compared with OA.

Thermal osteonecrosis is a side effect when used Kirschner (K) wires and drills in orthopaedic surgeries. This osteonecrosis may endanger the fixation. Orthopaedic surgeons sometimes have to use unsharpened K-wires in emergent surgery. The thermal effect of used and unsharpened K wire is ambiguous to the bone. This experimental study aims to assess the thermal osteonecrosis while drilling bone with three different types of K-wires especially a previously used unsharpened wire and its thermographic measurements correlation. Two different speeds of rotation were chosen to investigate the effect of speed on thermal necrosis to the bone.

A total of 16 New Zealand white rabbits weighing a mean of 2.90 kg (2.70 – 3.30 kg) were used. All rabbits were operated under general anaesthesia in a sterile operating room. Firstly, 4 cm longitudinal lateral approach was used to the right femur and then the femur was drilled with 1.0 mm trochar tip, spade tip and previously used unsharpened K-wires and 1.0 mm drill bit at 1450 rpm speed. Left femur was drilled with same three type K-wires and drill bit at 330 rpm speed. One cm distance was left among four penetrations on the femur. The thermal changes were recorded by Flir® E6 Thermal Camera from 50 cm distance and 30-degree angle. Thermographic measurements saved for every drilling process and recorded for the highest temperature (°C) during the drilling. All subjects were sacrificed post-operatively on the eighth day and specimens were prepared for the histological examination. The results of osteonecrosis assessment score and thermographic correlation were evaluated statistically.

Histological specimens were evaluated by the scoring of osteonecrosis, osteoblastic activity, haemorrhage, microfracture and inflammation. Results were graded semi-quantitatively as none, moderate or severe for osteonecrosis, haemorrhage and inflammation. The microfracture and osteoblastic activity were evaluated as present or absent. There was no meaningful correlation between osteonecrosis and the drilling speed (p=0.108). There was less microfracture zone which was drilled with trochar tip K-wires at 1450 rpm speed (p=0.017). And the drilling temperature of trochar tip K-wires was higher than the others(p=0.001). Despite this evaluation, osteonecrosis zone of spade and unsharpened tip K-wires were more than trochar tip K-wires (p=0.039). The drill bit at 330 rpm caused the least osteonecrosis and haemorrhage and respectfully the lowest drilling temperature (p=0,001). The osteoblastic activity shows no difference between the groups. (p=0,122; 0,636;0.289)

On the contrary to the literature, our experiment showed that there is no meaningful correlation between osteonecrosis score and temperature produced by drilling. The histological assessment showed the osteonecrosis during short drilling time but, not clarify the relation with drilling temperature. Eventually, the osteonecrosis showed a positive correlation with drilling time independently of drilling temperature at 330 rpm. (p=0,042) These results show that we need more studies to understand about osteonecrosis and its relationship with drilling heat temperature. Trochar tip K-wires creates higher drilling temperature but less osteonecrosis than a spade and unsharpened cut tip K-wires. Using unsharpened tip K-wire causes more osteonecrosis. Previously used and, unsharpened K-wires should be discarded

Introduction. Osteonecrosis of the femoral head (ONFH) is one of the most serious complications associated with corticosteroid therapy. In patients with ONFH, collapse of the femoral head often occurs and causes severe hip pain and impaired hip joint function. Despite the widely spread use of corticosteroids for treating various diseases and a known association between prevalence of ONFH and daily dose of corticosteroids, the pathomechanism for the development of ONFH has not been identified. Since hepatic cytochrome P4503A (CYP3A) is a predominant enzyme responsible for metabolizing corticosteroids and its activities varies more than 10-fold, low hepatic CYP3A activity leads to a remarkable increase of corticosteroid levels and its effect. We have previously reported that hepatic CYP3A levels are significantly lower in patients with corticosteroid-induced ONFH than that in control patients and patients with alcohol-related ONFH and that hepatic CYP3A activity inversely correlated with the incidence of osteonecrosis and extent of the necrotic area caused by the same dose of corticosteroids in a rabbit model, suggesting possible prevention of the corticosteroid-induced osteonecrosis by adjusting corticosteroid dose based on the level of individual hepatic CYP3A activity prior to corticosteroid therapy. To examine hepatic CYP3A activity, measuring clearance of administrated midazolam (MDZ) is a reliable method, as shown by the significant correlations between the clearance of midazolam and hepatic CYP3A levels measured by biopsy and the clearance of other CYP3A-specific substrates. However, the method is invasive and time consuming for measuring clearance of administrated MDZ, needing multiple blood samplings over half a day for each subject. The aim of this study was to develop the simple, safe and noninvasive methods for measuring the level of hepatic CYP3A activity, which is applicable to prevent the occurrence of corticosteroid-induced osteonecrosis prior to corticosteroid therapy. Methods. Thirty seven healthy male (n=20) and female (n=17), volunteers who had a mean age of 27 years received single oral administration of a small quantity of midazolam (50 mg/kg) and concentrations of total midazolam and its principal metabolite, 1-hydroxymidazolam (1-OH-midazolam), in each plasma at 15, 30, 45, 60, and 90 minutes and 2, 3, 4, 6, 9 and 12 hours post-drug administration were measured. Secondarily, the assessment of the Observer's Assessment of Alertness/Sedation (OAA/S) Scale was also used during the 12-hour post-administration period. Results. The best correlations between midazolam clearance and the ratio of 1- OH- midazolam/ midazolam plasma concentrations measured at each experimental time were observed at 4 hours (R2 = 0.83) post-dosing, and better correlations were found at 3 hours with a strong correlation (R2 = 0.81). Good correlations between midazolam clearance and OAA/S scale were found at 15 minutes (p = 0.04). Conclusion. A single midazolam plasma measurement taken at 4 hours post-oral administration may represent an accurate marker of CYP3A activity. This simple, safe and noninvasive method for measuring CYP3A activity could be used for patients prior to corticosteroid therapy, and the adjusting dose of corticosteroids, tailor-made medicine, depending on the CYP3A activity of the individual patient could avoid the occurrence of corticosteroid-induced osteonecrosis

Medial meniscus tear has been proposed as a potential etiology of spontaneous osteonecrosis of the knee (SONK). Disruption of collagen fibers within the meniscus causes meniscal extrusion, which results in alteration in load distribution in the knee. A recent study has demonstrated high incidence of medial meniscus extrusion in the knee with SONK. Our purpose was to determine whether the extent of medial meniscus extrusion correlates with the severity of SONK in the medial femoral condyle.

Anteroposterior and lateral knee radiographs were taken with the patients standing. Limb alignment was expressed as the femorotibial angle (FTA) obtained from the anteroposterior radiograph. The stage of progression of SONK was determined according to the radiological classification system described by Koshino. After measurement of anteroposterior, mediolateral, and superoinferior dimensions of the hypointense T1 signal intensity lesion of MRI, its ellipsoid volume was calculated with the three dimensions. Meniscal pathology (degeneration, tear, and extrusion) were also evaluated by MRI.

Of the 18 knees with SONK, we found 5 knees at the radiological stage 2 lesions, 9 knees at the stage 3, and 4 knees at the stage 4. Whereas the ellipsoid volume of SONK lesion significantly increased with the stage progression, the volume was significantly greater at stage 4 than stage 2 or 3. All the 18 knees with SONK in the present study showed substantial extrusion (> 3mm) and degeneration of the medial meniscus. While medial meniscal extrusion increased with the stage progression, medial meniscus was significantly extruded at stage 3 or 4 compared with stage 2. A significant increase in FTA was found with the stage progression. FTA was significantly greater at stage 4 than stage 2 or 3. Multiple linear regression analysis revealed that medial meniscus extrusion and FTA were useful predictors of the volume of SONK lesion.

This study has clearly shown a significant correlation between the extent of medial meniscus extrusion and the stage and volume of SONK lesion. Degeneration and tears of the medial meniscus in combination with extrusion may result in loss of hoop stress distribution in the medial compartment, which could increase the load in the medial femoral condyle. In addition to meniscal pathology, knee alignment can influence load distribution in the medial compartment biomechanically. Multiple linear regression analysis indicates that an increase in FTA concomitant with a greater extrusion of medial meniscus could result in greater lesion and advanced radiological stage of SONK. Taken together, alteration in compressive force transmission through the medial compartment by meniscus extrusion and varus alignment could develop subchondral insufficiency fractures in the medial femoral condyle, which is considered to be one of the main contributing factors to SONK development.

There was high association of medial meniscus extrusion and FTA with the radiological stage and volume of SONK lesion. Increased loading in the medial femoral condyle with greater extrusion of medial meniscus and varus alignment may contribute to expansion and secondary osteoarthritic changes of SONK lesion.