Summary Statement.
Introduction and Objective.
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.
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. 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.Introduction
Method
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.
Introduction.
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.
For many years, minimally invasive joint-preserving regenerative therapy has been desired for the early stages of osteonecrosis of the femoral head (ONFH). In an animal study using adult rabbits, we reported that a single local injection of rhFGF-2-impregnated gelatin hydrogel, which has superior slow-release characteristics, suppresses the progression of femoral head necrosis. The purpose of this study was to evaluate the safety and clinical outcomes of a single local administration of rhFGF-2-impregnated gelatin hydrogel for the precollapse stage of ONFH. Patients and Methods: Ten patients with femoral heads up to precollapse stage 2 underwent a single local administration of 800-µg rhFGF-2-impregnated gelatin hydrogel and were followed up for two years. The eligibility criteria were age between 20 and 80 years and presence of ONFH at precollapse stage 1 or 2 according to the classification system for ONFH developed by the Japanese Investigation Committee of Health and Welfare. Primary outcomes included adverse events and complications. Secondary outcomes included changes in Harris Hip Scores (HHS), visual analog scale pain scores (VAS), the University of California, Los Angeles (UCLA) activity rating scores, radiological changes as determined via radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI) of the hip joint. Results: We included five men (five hips) and five women (five hips), with a mean age of 39.8 years (range: 29–53 years) at the time of surgery. Eight patients had bilateral ONFH, three had already undergone THA on the contralateral side. Eight patients were receiving treatment with corticosteroid therapy, and two patients overused alcohol. Stage 1 and 2 disease was present in one and nine patients, respectively. One patient each had type A, type B, and type C1 disease, whereas seven patients had a type C2 lesion. All Adverse events were recovered without problem. The surgery was performed with a minimally invasive technique based core decompression (1 cm of skin incision), and walking was allowed from the day after surgery. Mean clinical scores improved significantly after three year compared with before surgery (before vs. after: VAS for pain, 21.2 vs. 5.3 mm; UCLA activity score 5.5 vs. 6.6; HHS, 81.0 vs. 98.4 points, respectively). There was only one case of femoral head collapse, and it had the greatest necrosis volume fraction and was considered to be in the early collapse stage at the time of operation. The other nine cases did not involve ONFH stage progression, and collapse was prevented. CT images and recent MRI postoperatively confirmed bone regeneration and reduction of the necrotic area. Conclusion: Clinical application of rhFGF-2-impregnated gelatin hydrogel for patients with precollapse stage of ONFH was feasible and safe. Our research is ongoing, further phase II multiple center study has been started in January 2016.Introduction
The crescent sign is thought to be an early indicator of collapse in osteonecrosis of the femoral head. However, the formation mechanism of the crescent sign is still not quite clear. The purpose of this study was to utilize the two-dimensional finite element model analysis (FEA) technique to analyze mechanical function of different structures and intraosseous fluid in the femoral head under the stress of physiological loading. We wished to answer the following question: which structure or structures' failure are the main causes of collapse in osteonecrosis of the femoral head (ONFH)? Based on two femoral head specimens obtained during THA (one with osteonecrosis of the femoral head with crescent sign formation and the other with most of the cancellous bone eroded by tumor cells without collapse), three groups of ten models were designed. Group A were standard femoral heads composed of subchondral plate, cancellous bone, intraosseous fluid, and cortical bone with 50 mm in diameter, Group B included ONFH, and Group C was based on a tumor-eroded femoral head. Previously reported mechanical property parameters were used in the FEA calculation. The strain and Von Mieses stress mechanics parameters of fifteen points (with the same coordinates) in the junction between subchondral plate and cancellous bone were harvested and compared.Introduction
Methods
Even in localized collapse due to osteonecrosis of the femoral head, a femoral head can be preserved by rotational osteotomy. In addition to anterior rotation, originally described by Sugioka, much more correction can be obtained by posterior rotation. But, transtrochanteric rotational osteotomy needs rather extensive soft tissue release, such as complete capsulotomy and resection of short external rotators and psoas tendons. Many patients tend to complain about the leg length discrepancy and limp due to varus change. We found soft tissue resection and limb shortening could be minimized by doing the osteotomy at the femur neck rather than the trochanteric area following the technique of surgical dislocation. It needs careful dissection of the posterior retinacular artery to preserve circulation to the femoral head. We have performed 17 cases (14 cases were in men and 3 cases were in women), and average patient age was 45 years old. Osteotomy was applied to cases with collapse or large necrotic region that seemed to be fail by core decompression. All cases showed collapse except one (ARCO 2-B) and 6 cases were ARCO 3-A, 5 cases were ARCO 3-B, 4 cases were ARCO 3-C and one case was ARCO stage 4. Seven cases were rotated anteriorly, and ten cases were rotated posteriorly. Amount of rotation was 63 to 170 degrees in posterior rotation (mean 100.8 degrees) and mean 48 degrees in anterior rotation. The size of the necrotic area was 301 degrees according to the Koo method (combined necrotic angle in mid-coronal and mid-saggital MRI scan).Introduction
Methods
Hip resurfacing has become a popular procedure for young active patients with osteonecrosis of the femoral head. However, it is not yet clear exactly how much osteonecrosis would permit this procedure and how much would be a contraindication. The aim of the present study was to analyze the resurfaced femoral head using finite element models and, in particular, to examine the influence of the extent of osteonecrosis and metaphysical stem shaft angles within the femoral head. We evaluated biomechanical changes at various extents of necrosis and implant alignments, using the finite element analysis method. We established three patterns of necrosis by depth from the surface of femoral head and five stem angles. Extension of necrosis as a quarter of femoral head diameter is type A, from a half is type B, and three-fourths is type C. We set five types of different stem angles from 125 to 145 degrees for the axis of femoral shaft. For these models, we evaluated biomechanical changes associated with the extent of necrosis and the stem alignment.Introduction
Methods
Since 2005, we have performed implantation of bone marrow-derived mononuclear cells for osteonecrosis of the femoral head in order to improve vascularization and bone repair. This study focused on early bone repair of osteonecrosis of the femoral head after transplantation of bone marrow-derived mononuclear cells (BMMNC). Twenty-two patients (30 joints) who had bilateral osteonecrosis followed for more than 2 years after BMMNC implantation were evaluated. Eight women and 14 men were included. Their mean age at surgery was 41 years (range, 18 to 64 years) and the mean follow-up period was 31 months. Pre-operative stage according to the ARCO classification was Stage 2 in 25 joints and Stage 3 in 5 joints. The mean volume ratio of osteonecrosis was 21%. For preparing BMMNC, about 700ml of bone marrow was aspirated from the ilium and centrifuged using a Spectra cell separator (Gambro). The BMMNC were seeded to interconnected porous calcium hydroxyapatite (IP-CHA) and implanted to the osteonecrotic lesion. As a control, cell-free IP-CHA was implanted for 8 patients (9 joints). A woman and 7 men were included. The mean age at surgery was 49 years (range, 28 to 73 years) and the mean follow-up period was 37 months. Preoperative stage was stage 2 in all patients. The mean volume ratio of osteonecrosis was 22%. At post-operative evaluations; progression of collapse, consolidation at reactive zone, post-operative course of volume rate of osteonecrosis, and bone absorption at osteonecrosis was assessed.Introduction
Patients and Methods
In osteonecrosis of the femoral head (ONFH), progression of collapse is influenced by a repair reaction, especially bone resorptive activity, around the necrotic bone. Alendronate is a potent inhibitor of bone resorption by inhibiting osteoclast activity. We performed a clinical study to test if systemic alendronate treatment would prevent the development of collapse in patients with ONFH. Thirty-three hips in 22 ONFH patients with initial ARCO Stage 1 to 3 were included. Fourteen patients (20 hips) received daily administration of oral alendronate 5mg/day (alendronate group) and 8 patients (13 hips) did not receive alendronate administration (Control group). Baseline investigations included anteroposterior and lateral plain radiographs, T1-weighted magnetic resonance imaging (MRI), and biochemical markers (urinary NTX and serum BAP). Examination of the biochemical markers were repeated at 3, 6, and 12 months, and MRI imaging was repeated at 12 months. At 3 years, clinical symptoms and findings on plain radiographs were compared between the 2 groups. Advancement of ARCO stages or increase of collapse by more than 2 mm were considered as development of collapse.Introduction
Methods
Transtrochanteric curved varus osteotomy is one of the effective joint-preserving operations for osteonecrosis (ON) of the femoral head. We correlated various factors with the radiological outcome of this procedure. We reviewed 74 hips in 63 patients who had a minimum follow-up of 5 years after transtrochanteric curved varus osteotomy for the treatment of ON. There were 28 men and 35 women who had a mean age of 33 years (range, 15 to 68 years) at the time of surgery. Clinical assessment was made based on the Harris hip score (HHS). Radiographically, we investigated various factors; affected lesion, stage and type (localization of the necrotic lesion) of ON, varus degree, post-operative intact ratio, progression of collapse, and joint-space narrowing. On the basis of postoperative radiographs, the hips were divided into 2 groups (Group I: either the progression of collapse or joint-space narrowing, Group II: neither progression of collapse or joint-space narrowing). The related factors with radiological outcome were analyzed by using multivariate analysis (Stepwise discriminant analysis).Introduction
Methods
The purpose of this study was to investigate the long-term outcome of Sugioka's transtrochanteric rotational osteotomy (TRO) for nontraumatic osteonecrosis of the femoral head. Seventy-eight patients (87 hips) were consecutively treated by TRO from 1989 to 1994. All patients followed 15 years or more were included. Four patients (4 hips) with traumatic osteonecrosis and five patients (5 hips) followed less than 15 years were excluded. A total of 69 patients (78 hips) were included. Average age at the time of operation was 42 years. There were 51 men (57 hips) and 18 women (21 hips). The average follow-up was 17 years (range, 15 to 20 years). Type of osteonecrosis was as follows: Type B; 2 hips, Type C1; 50 hips, and Type C2; 26 hips. Stage was as follows: stage 2; 29 hips, stage 3A; 34 hips, stage 3B; 13 hips, and stage 4; 2 hips. Transtrochanteric anterior rotational osteotomy was performed in 76 hips and posterior rotational osteotomy was performed in 2 hips. Clinical evaluation was evaluated by Harris hip score. Kaplan-Meier survivorship analysis was performed based on the end point of conversion to total hip arthroplasty (THA) or re-collapse.Introduction
Methods
The treatment osteonecrosis of the femoral head remains uncertain. Core decompression is the standard technique for the early stages (ARCO I and II). A new alternative is core decompression combined with the insertion of an osteonecrosis rod. This implant is supposed to reduce the intraosseous pressure and to give additional structural support. The aim of this study was to evaluate the clinical and radiological outcome via magnetic resonance imaging (MRI) of this new technique. Twenty-three patients were included in this study. All patients underwent a core decompression combined with the insertion of an osteonecrosis rod.Introduction
Methods
What is the most effective treatment of the early stages for osteonecrosis of the femoral head? Since the results of several treatment modalities such as multiple drilling, core decompression with or without bone graft, and vascularized fibular grafts have not been completely successful, we tried multiple drilling and stem cell transplantation to treat the early stages of osteonecrosis of the femoral head and to minimize patient morbidity. We report the clinical and radiological results of stem cell transplantation and core decompression. One hundred and twenty-eight patients (190 hips) who had undergone surgery were divided in two groups based upon which treatment they had received: (1) multiple drilling and stem cell transplantation, and (2) core decompression, curettage, and bone graft. The clinical and radiological results of the two groups were compared. We defined failure as the need for additional surgery, or a Harris hip score of less than 75 points.Introduction
Methods
The purpose of this study was to evaluate the outcome of vascularized iliac bone grafting for idiopathic osteonecrosis of the femoral head. We reviewed the clinical and radiological results of 35 operations performed on 29 patients who had osteonecrosis of the femoral head (ONFH) in which a pedicle iliac bone grafting was performed for minimum follow-up of 10 years. The average age was 35 years (range, 17 to 62 years). According to the Japanese Orthopaedic Association classification for ONFH, there were 28 stage 2, 7 stage 3-A, 17 type C-1 hips, and 18 type C-2 hips. After a bone tunnel of 1.5 × 5 cm was made in the anterior aspect of the femoral head and curettage of necrotic lesion was performed, the pedicle bone with the deep circumflex iliac artery (DCIA) was inserted into the anterolateral portion of the femoral head. The average follow-up period was 13 years and 6 months. Weight bearing was not allowed for 2 months after the operation. Survival rate of the femoral head was calculated by Kaplan-Meier methods, and collapse of the femoral head and configuration of the femoral head was investigated at final follow-up.Introduction
Methods
