Pathogenesis Of Femoral Head Necrosis Research Articles

Autophagy in Femoral Head Necrosis of Broilers Bone Metabolism Parameters and Autophagy-Related Gene Expression in Femoral Head Necrosis Induced by Glucocorticoid in Broilers.

Objectives: In this study, the influence of methylprednisolone (MP) and 3-methyladenine (3-MA) on chondrocyte autophagy and bone quality were determined to investigate the mechanisms of femoral head necrosis in broilers.Methods: Chickens were divided into four groups: control, MP, 3-MA, and 3-MA+MP groups. Blood and bone samples were collected for biochemistry assay and bone quality determination. Cartilage was separated from the femoral head for histopathological analysis and gene expression detection.Results: The results indicated that MP treatment significantly affected blood levels of alkaline phosphatase, high-density lipoprotein, calcium, phosphorus, bone alkaline phosphatase, and osteocalcin in broilers. Additionally, MP treatment significantly increased blood levels of cholesterol, low-density lipoprotein, triglyceride, carboxy-terminal telopeptide of type-I collagen, and tartrate-resistant acid phosphatase 5. MP treatment also significantly decreased the levels of bone parameters compared with these values in controls, inhibited the expression of collagen-2, aggrecan, and mammalian target of rapamycin, and increased the expression of beclin1 and microtubule-associated protein 1 light chain 3, hypoxia-inducible factor 1 alpha, phosphoinositide 3-kinase, protein kinase B and autophagy-related gene 5 of the femoral head. Furthermore, following co-treatment with 3-MA and MP, 3-MA mitigated the effects of MP.Conclusions: Our findings demonstrated that autophagy may be involved in the pathogenesis of femoral head necrosis induced by MP in broilers, and this study provides new treatment and prevention ideas for femoral head necrosis caused by glucocorticoids.

Bone characteristics, histopathology, and chondrocyte apoptosis in femoral head necrosis induced by glucocorticoid in broilers

Femoral head necrosis (FHN) is a common disorder in fast-growing broilers in the poultry industry, but the pathogenesis of FHN has not been clarified completely. In the present study, glucocorticoid (GC) administration was used to induce FHN in broilers. Compared with normal birds, histopathology showed that the length of the articular cartilage of GC-induced FHN broilers was thicker while the proliferative zone and prehypertrophic zone were obviously thinner. Moreover, hematoxylin and eosin (HE) staining showed the apoptotic chondrocyte in the growth plate of the femoral head in FHN-affected birds. Bone parameters also decreased significantly in GC-induced FHN broilers. In addition, as for the mRNA expression, GC-induced FHN broilers had an apparent reduction in Col-II, Col-X, and Bcl-2 but a significant promotion of Caspase-3, Caspase-9, ASK-1, and JNK-1 when compared with the normal birds. It showed glucocorticoid induced FHN in broilers by affecting the proliferation, differentiation, and apoptosis of chondrocytes accompanying the retarding of bone growth.

Bone circulatory disturbances in the development of spontaneous bacterial chondronecrosis with osteomyelitis: a translational model for the pathogenesis of femoral head necrosis

This review provides a comprehensive overview of the vascularization of the avian growth plate and its subsequent role in the pathogenesis of bacterial chondronecrosis with osteomyelitis (BCO, femoral head necrosis). BCO sporadically causes high incidences of lameness in rapidly growing broiler (meat-type) chickens. BCO is believed to be initiated by micro-trauma to poorly mineralized columns of cartilage cells in the proximal growth plates of the leg bones, followed by colonization by hematogenously distributed opportunistic bacteria. Inadequate blood flow to the growth plate, vascular occlusion, and structural limitations of the microvasculature all have been implicated in the pathogenesis of BCO. Treatment strategies have been difficult to investigate because under normal conditions the incidence of BCO typically is low and sporadic. Rearing broilers on wire flooring triggers the spontaneous development of high incidences of lameness attributable to pathognomonic BCO lesions. Wire flooring imposes persistent footing instability and is thought to accelerate the development of BCO by amplifying the torque and shear stress imposed on susceptible leg joints. Wire flooring per se also constitutes a significant chronic stressor that promotes bacterial proliferation attributed to stress-mediated immunosuppression. Indeed, dexamethasone-mediated immunosuppression causes broilers to develop lameness primarily associated with avascular necrosis and BCO. Prophylactic probiotic administration consistently reduces the incidence of lameness in broilers reared on wire flooring, presumably by reducing bacterial translocation from the gastrointestinal tract that likely contributes to hematogenous infection of the leg bones. The pathogenesis of BCO in broilers is directly relevant to osteomyelitis in growing children, as well as to avascular femoral head necrosis in adults. Our new model for reliably triggering spontaneous osteomyelitis in large numbers of animals represents an important opportunity to conduct translational research focused on developing effective prophylactic and therapeutic treatments.

Role of hypercoagulability in steroid-induced femoral head necrosis in rabbits

BackgroundThe pathogenesis of femoral head necrosis is still uncertain. Both steroid treatment and hypercoagulopathy are considered risk factors. To investigate possible changes in coagulability and histology during steroid-induced osteonecrosis, we used a combination of the Shwartzman reaction and corticoid injections in rabbits to develop an animal model of femoral head necrosis. We studied blood coagulability and histopathological characteristics of the femoral head and liver. MethodsA total of 30 rabbits were divided into three groups. In group A, rabbits were given two injections of lipopolysaccharide (40μg/kg) at an interval of 24h and were then immediately given one injection of prednisolone acetate (20mg/kg). In group B, 10 rabbits were given one injection of prednisolone acetate (20mg/kg). In group C, 10 rabbits were given no treatment and served as controls. At 1, 3, 7, 14, and 21 days after prednisolone injection, coagulability, blood lipid levels, and blood platelet levels were measured; and the femoral head and liver were removed for histopathological examination. ResultsAt 24h after the prednisolone injection in group A, coagulability and blood lipid levels were increased (P < 0.01), and blood platelet levels were decreased (P < 0.01). These abnormal levels were maintained throughout the entire observation period. Histologically, degeneration and necrosis of hepatocytes and osteocytes were found at day 21 after prednisolone injection in group A. In group B, coagulability and blood lipid levels were signifi cantly increased by day 3 after treatment. ConclusionsAbnormal hypercoagulability might potentiate the thrombotic status and induce thrombus formation in the presence of steroid-induced necrosis of the femoral head.

Femoral head histology subsequent to ischemia, reperfusion and steroid treatment

An episode of ischemia followed by reperfusion of the femoral head (FH) is thought to be a common pathway in the pathogenesis of femoral head necrosis (FHN). Femoral head histology was investigated after short-term high-dose steroid treatment and femoral head ischemia and reperfusion in a large animal model. Twenty-two pigs were randomized to receive methylprednisolone 20 mg/day/kg bodyweight intamuscularly for 3 days followed by methylprednisolone 10 mg/day/kg bodyweight for 11 days ( n=11), whereas the control group ( n=11) received no treatment. After 6 h of unilateral hip-joint pressure increase to 250 mmHg, the pressure was discontinued and reperfusion was allowed for 4 h. Undecalcified histology was performed for the femoral head subchondral region, the mid-region, and the region adjacent to the growth plate. Congestion phenomena were predominantly discerned in femoral head sections of the tamponaded hips. Histomorphometry revealed fat cell hyperthrophy and reduced hemopoetic marrow cells in the femoral heads of the steroid-treated group of animals. The number of blood vessels and bone trabeculae remained unchanged. These characteristics may correlate with early-stage femoral head necrosis.

Thrust plate prosthesis for osteonecrosis of the femoral head: Short-term results of 15 patients followed 2–6 years

BackgroundThe thrust plate prosthesis is an implant with a metaphyseal fixation at the proximal femur that transmits the load forces of the hip onto the femoral neck. MethodsIn this prospective study, 15 patients (8 women, 7 men) with 19 cementless thrust plate prostheses because of femoral head necrosis were examined. A clinical and radiologic evaluation was performed preoperatively, at 3, 6, 12, 18, and 24 months postoperatively, and every year thereafter. The mean follow-up period was 44 (range, 24–72) months. The average age at the time of surgery was 49 (27–70) years. The pathogenesis of femoral head necrosis included alcoholism (6 joints of 3 cases), Gaucher disease (1 joint of 1 case), Sheehan syndrome (2 joints of 1 case), and idiopathic (10 joints of 10 cases). ResultsThe Harris hip score increased from 53 (range, 15–71) to 97 (92–100) points on the final evaluation. Although mean preoperative hip flexion and abduction were 78° (45°–110°) and 24° (10°–45°), respectively, these increased to 114° (75°–125°) and 47° (45°–50°) 12 months after surgery and remained stable up to the latest follow-up. None of the patients displayed mechanical problems, and revision was not necessary in any case. ConclusionsThe thrust plate prosthesis shows midterm results comparable to those of the cementless stemmed prosthesis and supplies advantages, especially for younger patients with femoral head necrosis, because of its metaphyseal bonepreserving fixation.

Effect of methylprednisolone on reperfusion after femoral head ischemia.

An episode of ischemia and reperfusion of the femoral head is thought to be the common pathway in the pathogenesis of femoral head necrosis. The influence of short-term high-dose steroid treatment on femoral head reperfusion after ischemia was investigated in a porcine model. Twenty-two pigs were randomized to receive methylprednisolone 20 mg/day/kg bodyweight intramuscularly for 3 days followed by methylprednisolone 10 mg/day/kg bodyweight for 11 days (n = 11), whereas the control group (n = 11) received no treatment. Femoral head ischemia was achieved by 6 hours of unilateral intraarticular hip pressure increase to 250 mm Hg. Femoral head blood flow was estimated using radiolabeled microspheres (15 microm in diameter) before ischemia, during hip tamponade, and 4 hours after tamponade release. Femoral head blood flow was lower in the corticosteroid treated pigs. Subtotal femoral head ischemia was documented in both groups during joint tamponade. Apart from two femoral head epiphyses in either group, reperfusion after tamponade release on the average occurred to a blood flow level similar to that before ischemia. Short-term high-dose methylprednisolone treatment depressed bone perfusion in general, but had no effect on reperfusion after femoral head ischemia in the porcine model.

The thrust plate prosthesis in patients with aseptic osteonecrosis of the femoral head.

The thrust plate prosthesis (TPP) is an implant with a metaphyseal fixation at the proximal femur that transmits the load forces of the hip onto the femoral neck. The osseous incorporation of the TPP and the adaptation of the bone to this force transmission depend on the bone quality, which is reduced to minor vitality and stability in patients with osteonecrosis of the femoral head. Depending on the etiology of the femoral head necrosis, the TPP might lead to early failures. In a prospective study, 63 patients with 72 cementless TPP due to femoral head osteonecrosis were examined. A clinical and radiological evaluation was performed preoperatively, 3 and 6 months postoperatively, and every year thereafter. The average follow-up period was 4.8+/-1.3 years with a minimum of 3 years. The pathogenesis of femoral head necrosis included alcoholism (n=19), subsequent to renal transplantation (n=11), during cortisone therapy of other dyscrasia (n=9), preceding a polychemotherapy (n=4), diabetes (n=3), sickle cell anemia (n=1), and idiopathic osteonecrosis (n=25). The Harris Hip Score increased continuously from 50.0 points beyond 79.8 points after 3 months to 86.8 points within the 1st year, and subsequently remained stable at this level. Revision was necessary in six cases (8.3%). Of these, three had an aseptic loosening of the implant: 2 cases with renal transplantation and 1 of alcoholism with an extension of the necrotic area to the seating of the TPP. The other three patients showed septic implant loosenings: 2 cases with renal transplantation and 1 of alcoholism. Radiolucent lines were found in 9 cases (12.5%), mostly in zones 1 and 2 underneath the TPP. Of these, 1 with an idiopathic osteonecrosis was assessed to be radiologically loosened. The overall failure rate was 9.7%, with a proportion of 36.4% in patients with renal transplantation. Excluding this specific patient group, the failure rate was 4.9%. Femoral head necrosis following renal transplantation and extension of the necrotic area into the femoral neck are contraindications for TPP. Excluding these patients, the TPP shows comparable mid-term results to cementless stemmed prostheses and supplies advantages especially for younger patients, because of its metaphyseal, bone-preserving fixation. However, evaluation of the clinical impact of the TPP in comparison with other cementless femoral stem systems requires long-term examinations in the future.

Fracture of the Femoral Neck

The opinion is widely held that interruption of the arterial flow through the retinacular arteries to the femoral head is the main cause of avascular necrosis after fracture of the neck. In this study the state of the vascular supply to the femoral head was assessed--prior to osteosynthesis--by means of intramedullary pressure measurements in the femoral head and neck in 72 patients with medial neck fractures. The patients were followed 2 or 3 years or until avascular necrosis became evident. The relative importance of primary avascularity and surgical technique for the development of necrosis suggests that damage to the retinacular arteries may not be the single decisive factor in the pathogenesis of femoral head necrosis. Proper fracture reduction with extensive contact between the cancellous bone surfaces and stable fixation seemed to be more important, probably because they offer the best possibilities for re-establishment of transosseous blood flow across the fracture site.