Alcohol-induced Osteonecrosis Of The Femoral Head Research Articles

The related gene expression in necrotic tissue of alcohol-induced osteonecrosis of the femoral head necrosis in advanced stage

Objective To observe the related gene expression levels in the necrotic tissue of the alcohol-induced osteonecrosis of the femoral head (ONFH) in advanced stage.Methods The 20 femoral heads have been gathered during THA from 10 patients with the alcohol-induced ONFH in advanced stage as the experimental group,and from 10 patients with fracture of femoral neck as the control group.The expression levels of bone morphogenetic protein-2 (BMP-2),Runt-related transcription factor-2 (Runx-2),peroxisome proliferator-activated receptor-γ (PPAR-γ),osteoprotegerin (OPG),receptor activator of NF-κB ligand (RANKL) mRNA in the bone-marrow cells of necrotic tissue of the femoral head of all patients were measured by real-time quantitative polymerase chain reaction(Real-time PCR).Results The expression levels of BMP-2,Runx-2,PPAR-γ,OPG and RANKL mRNA in the experimental group were significantly lower than those in the control group.2-△△Ct values of BMP-2,Runx-2,PPAR-γ,OPG and RANKL in the experimental group were 0.51 ± 0.04,0.46 ± 0.09,0.59 ± 0.07,0.31 ± 0.04 and 0.52 ±0.06,respectively,with the differences being statistically significant between two groups (P ＜ 0.01).Conclusion The very large size of necrotic tissue area was seen in the alcohol-induced ONFH in advanced stage,ARCO Ⅲ-C,Ⅳ.There were few of bone active ingredients and residual surviving bonemarrow cells in the femoral head,and the expression level of osteogenic and adipogenic genes in the cells was very lower.The femoral head has been seriously damaged,which is suitable for the total hip arthroplasty. Key words: Alcohol; Osteonecrosis of the femoral head ; Advanced stage; Gene ; Reduced

Quality of sexual life after total hip arthroplasty in male patients with osteonecrosis of femoral head

Patients with osteonecrosis of the femoral head (ONFH) have a severe impact on their health status, functionality and quality of life. Sexual life is an important component of the quality of life and is still a frequently neglected domain in patients with ONFH. The aims of the study were to evaluate the influence of the disease and the total hip arthroplasty (THA) surgery on quality of sexual life (QSL) in these patients. A prospective, self-controlled study was done. 247 patients of ONFH who underwent unilateral or bilateral THA were asked to complete a standardized QSL questionnaire, and the score of QSL was evaluated preoperatively and at first year follow-up of post-THA operation. The mean age of the patient was 46.8 (range 25-60) years. 194 cases (78.5%, 276 hips) were alcohol-induced ONFH. There is significant decrease (p = 0.026) in sexual relationship impairment on the 0-8 scale from pre-THA (5.3 ± 0.7) to post-THA (2.3 ± 0.4). There is no significant difference for effect on sexual function (p = 0.14) between pre-THA (2.3 ± 0.4) and post-THA (1.8 ± 0.3). There is significant improvement (p = 0.018) in overall sexual satisfaction degree of patients on the 1-5 scale from pre-THA (2.7 ± 0.2) to post-THA (4.7 ± 0.6), but no significant increase for sexual partner. ONFH has impaired relationships with partner and overall sexual satisfaction degree of the male patients; THA has improved significantly relationships with partner and overall sexual satisfaction degree of the male patients, but no effect on sexual function of the patients and overall sexual satisfaction degree of sexual partner.

Experimental rat model for alcohol‐induced osteonecrosis of the femoral head

Alcohol-induced osteonecrosis of the femoral head (ONFH) is observed in alcohol abusers and patients with alcoholic fatty liver disease. It has been reported that Toll-like receptor 4 (TLR4) signalling plays a crucial role in the pathogenesis of alcoholic fatty liver disease. We previously reported a corticosteroid-induced ONFH rat model, and suggested that TLR4 signalling contributes to the pathogenesis of ONFH. Thus, it is thought that the pathogenesis of alcohol-induced ONFH is probably similar to that of corticosteroid-induced ONFH. The aim of this study was to develop a new animal model for alcohol-induced ONFH and to evaluate the relationship between the pro-inflammatory response via TLRs and the development of ONFH in rats. Male Wistar rats were fed a Lieber–DeCarli liquid diet containing 5% ethanol (experimental group) or dextran (control group) for 1–24 weeks. Histopathological and biochemical analyses were performed. Feeding the ethanol-containing liquid diet resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction and hyperlipidaemia, whereas feeding the dextran-containing diet did not cause ONFH. However, we could not recognize any relationship between the pro-inflammatory response via TLR4 and the development of alcohol-induced ONFH. Thus in this study we have developed a new rat model for alcohol-induced ONFH based on the feeding of an ethanol liquid diet. ONFH was observed within seven days from the start of feeding with 5% ethanol-containing liquid diet. Although this was linked to hepatic steatosis, a TLR4 association was not a feature of this model.

Application of CFP short-stem prosthesis in the treatment of osteonecrosis of the femoral head

To investigate the clinical outcome for the treatment of osteonecrosis of the femoral head (ONFH) in advanced stage by a short-stem prosthesis preserving femoral neck in total hip arthroplasty (THA). From June 2008 to December 2009, 9 hips in 8 patients with advanced stage of ONFH were treated by a short-stem preserving femoral neck in THA. The mean age was 24.1 years (range: 20 - 36). There were 3 patients (3 hips) with alcohol-induced ONFH and 5 patients (6 hips) with steroid-induced ONFH. According to the classification of Association Research Circulation Osseous (ARCO), 7 hips were in stage III-C and 2 hips in stage IV respectively. The clinical outcomes were evaluated according to the Harris evaluation score and radiographic analysis. All patients were followed up for a mean duration of 18.1 months (range: 12 - 30). The mean Harris hip score improved from preoperative (42.8 ± 8.6) points to (92.8 ± 6.1) points at the time of final follow-up. The outcomes were excellent in 7 hips and better in 2 hips. Neither osteolysis of mortar and femur nor loose component was found from radiological films. The pain of all hips disappeared and no complications occurred. The short-term clinical outcome is satisfactory for treating young patients with advanced stage of ONFH by a short-stem prosthesis preserving femoral neck in THA.

A peroxisome proliferator‐activated receptor gamma (PPARG) polymorphism is associated with zoledronic acid‐related osteonecrosis of the jaw in multiple myeloma patients: analysis by DMET microarray profiling

A peroxisome proliferator‐activated receptor gamma (<i>PPARG</i>) polymorphism is associated with zoledronic acid‐related osteonecrosis of the jaw in multiple myeloma patients: analysis by DMET microarray profiling

Prevention of alcohol-induced osteonecrosis of femoral head in rabbits by small interfering RNA targeting specific gene by gavage

Objective To observe the effect of small interfering RNA (siRNA) adenovirus vectors targeting PPARγto prevent the alcohol-induced osteonecrosis of the femoral head (ONFH) in rabbits.Methods Ninety-six rabbits were randomly divided into four groups. In group N, normal saline ( 10 ml/kg every day) was poured into stomach. In group M, the strong wine (the volume fraction was 46% alcohol,10 ml/kg every day) was poured into stomach. In group S, under the randomly selected side and anesthesia, the animals were injected with 25 μl siRNA adenovirus drip into the femoral head and then the puncture hole was closed on the 1st day at the 1st, 3rd and 5th month of the experiment, and at the same time the strong wine (the volume fraction was 46% alcohol, 10 ml/kg every day) was poured into stomach. In group CO, animals were treated with the same method as the group S, but not injected with siRNA adenovirus drip. The animals were sacrificed in batches at 2nd, 4th and 6th month after the experiment. The serology and pathological changes of the femoral head were studied. Results At the 6th month, the triglyceride (TG, mmol/L) contents in groups N, M, CO and S were (1.21 ±0. 12), (4.59 ± 1.58), (4.63 ±1.17) and (4. 32 ± 1.20), the cholesterol levels ( CHO, mmol/L) were (2. 35 ± 0. 33), ( 19. 59 ±1.58), (20. 13 ± 1. 17) and ( 18.32 ± 1.20), the average diameter of the max adipocyte (μm) was (40. 89 ± 2. 41 ), (48.65 ± 2.93 ), (49. 45 ± 2. 63 ) and ( 42. 52 ± 2. 57 ), the trabeculace area fraction was (41.80 ±2. 47)%, (30. 70 ±2. 86)%, (29. 80 ±2. 69)% and (41.60 ±2. 87)%, the percentage of empty osteocyte lacunae was (12.30 ± 1.73)%, (22.40 ± 1.52)%, (23. 10 ± 1.62)% and (11.70 ±1.46)%, the expreasion levels of PPARγ mRNA were (0.29 ±0.05), (0.66±0. 12), (0.61±0.15) and (0. 33 ± 0. 05 ), the expression levels of osteocalcin mRNA were (0. 92 ± 0. 07 ), (0. 19 ± 0. 11 ), (0. 23 ±0. 08) and (0. 88 ± 0. 11 ), the expression levels of PPARγprotein were ( 0. 75 ± 0. 08 ), ( 1.60 ± 0. 11 ),(1.55 ±0. 12) and (0.65 ±0.05), respectively. In groups M and CO, the pathological changes were obvious; there was decreased hematopoietic tissue, proliferation and hypertrophy of the adipocytes, increased fatty tissue, and thinned, sparse or breoken bone trabeculae in the femoral head; the area fraction of the trabeculae was reduced. In group S, the average diameter of the max adipocyte, percentage of empty osteocyte lacunae, incidence of ONFH, the expressions of PPARγmRNA and protein were obviously reduced as compared with groups M and CO (P ＜0. 01,P ＜0. 05). There was no statistically significant difference between group S and group N (P ＞ 0. 05). Conclusion siRNA adenovirus vectors targeting PPARγcan efficaciously suppress the expression of PPARγ gene and adipogenic differentiation of the MSCs in the femoral head induced by alcohol, which may prevent the development of the alcohol-induced ONFH in rabbits. Key words: siRNA; PPARγ; Alcohol; Osteonecrosis of femoral head; Rabbit; Prevent

MyD88‐independent pathway plays an important role in alcohol‐induced osteonecrosis

ObjectivesOsteonecrosis of the femoral head (ONF) occurs under steroid therapy or chronic alcohol consumption. Most of patients with alcohol‐induced ONF contract alcoholic fatty liver disease, in the pathogenesis of which LPS, a ligand of TLR4, plays a crucial role. However, the pathogenesis of alcohol‐induced ONF remains unclear. In the present study, we found that feeding alcohol liquid diet for experimental alcoholic fatty liver disease causes ONF and clarified role of proinflammatory responses in the pathogenesis.MethodsMale Wistar rats were fed Lieber DeCarli liquid diet containing 5% ethanol or dextran for 1–6 weeks. Histopathological and biochemical analyses were performed.ResultsAlcohol liquid diet feeding remarkably promoted ONF. The animal had hepatic steatosis, liver dysfunction, and hyperlipidemia as well as many previous reports. Blood IFN gamma was increased in the rat fed with alcohol liquid diet, while adiponectin levels was decreased in the rat. IFN gamma and adiponectin can be related to TLR4 understream pathways via MyD88‐independent and dependent.ConclusionsWe found ONF in the rat fed alcohol liquid diet. The animal showed elevated IFN gamma and decreased adiponectin, suggesting that IFN gamma signaling pathway may play a crucial role in the pathogenesis of alcohol‐induced osteonecrosis of the femoral head.

Clinical observation of deliquesce strut with titanium web and cage containing bone grafting pedicled with femoral quadratus to treat non-traumatic osteonecrosis of the femoral head

objective To investigate the clinical outcome for the treatment of nontraumatic os-teonecrosis of the femoral head (ONFH) by a technique of deliquesce strut with titanium web and cage con-taining bone grafting pedicled with femoral quadratus.Methods Sixteen adult patients (20 hips) suffered from non-traumatic ONFH underwent the surgery of the deliquesce strut with titanium web and cage contain-ing bone grafting pedicled with femoral quadratus from January 2008 to June 2009.The mean age was 30.4 years (21-46).The steroid-induced ONFH was in 2 patients (4 hips),alcohol-induced ONFH in 14 patients (16 hips).According to Association Research Circulation Osseous (ARCO) classification,4,14 and 2 hips were in stage ⅡB,ⅡC and ⅢA.respectively.The results were followed and evaluated by the method of hundred percent score.Results The mean operation time was 155 minutes.The mean blood loss was 420 ml.All the wounds healed uneventfully.Anticoagulation medicine was not routinely used,and no deep vein thrombus (DVT) occurred.All patients were followed for an average time of 12.1 months (range,3 to 15 months).Weight-bearing was permitted 4 months postoperatively.Pain disappeared or significantly improved in all hips with hip function improved greatly.Bong-grafting healing was noted 3 to 4 months postoperatively.The normal height of the femoral head was maintained in 18 hips.Collapse occurred in 2 hips.There were resuits of excellent in 16 hips and better in 4 hips in this group.Conclusion For non-traumatic ONFH in stage ARCO ⅡC or ⅢA,satisfactory clinical outcome can be achieved by the new technique in the short-term period,the long-term clinical outcome has yet to be observed. Key words: Femur head necrosis; Transplantation; autologous; Treatment outcome

Apoptosis in the Osteonecrosis of the Femoral Head

BackgroundOsteonecrosis of the femoral head is classified into idiopathic and secondary forms. A number of etiological factors in the development of osteonecrosis have been suggested but the biological mechanisms are still unclear. Recently, some reports suggested that the apoptosis is closely related to osteonecrosis of the femoral head. Therefore, this study examined the expression of apoptosis in osteonecrosis of the femoral head.MethodsOf the patients diagnosed preoperatively with osteonecrosis and underwent total hip replacement arthroplasty between August 2004 and July 2005, 58 patients (58 hips) were available for this study. Their diagnoses were confirmed by the postoperative pathology findings. Tissue samples of the femoral head sections were terminal deoxynucleotydyl transferase mediated dUTP nick-end labeling (TUNEL) stained using an in situ cell death detection POD kit. The number of total and TUNEL-positive osteocytes, and the average ratio of TUNEL-positive cells were calculated and analyzed according to the cause.ResultsOsteonecrosis was steroid-induced in 8 cases (13.8%), alcohol-induced in 29 cases (50%), post-traumatic in 6 cases (10.3%) and idiopathic in 15 cases (25.9%). The percentage of TUNEL-positive osteocytes was high in patients with steroid- and alcohol-induced osteonecrosis of the femoral head but low in patients with post-traumatic and idiopathic osteonecrosis. The difference in the percentage of TUNEL-positive osteocytes between these groups was significant (p < 0.05).ConclusionsApoptosis might play an important role in the pathogenesis of osteonecrosis of the femoral head induced by steroid and alcohol. These findings highlight a need for further research into the role of apoptosis in the development of osteonecrosis of the femoral head.

Association of a Polymorphism in the Intron 7 of the SREBF1 Gene with Osteonecrosis of the Femoral Head in Koreans

Reduction or disruption of the blood supply to the bone is involved in the pathogenesis of osteonecrosis of the femoral head (ONFH). An altered lipid metabolism is one of the major risk factors for ONFH. Sterol regulatory element binding protein, SREBF1 activates genes regulating lipid biosynthesis. The aim of this study was to examine the association between the polymorphisms of the SREBF1 gene and ONFH susceptibility in the Korean population. The SREBF1 gene in 24 unrelated Korean individuals was sequenced and two polymorphisms were detected. Two variants, IVS6 - 48 C > T and IVS7 + 117 A > G, were genotyped in 423 ONFH patients and 348 controls. The genotype frequency of IVS7 + 117 A > G in ONFH patients was significantly different from that of the control group with P value < 0.0001 (Adjusted OR; 6.88, 95% CI; 3.74-12.67). Moreover, the IVS7 + 117 A > G genotype showed an association with men, and further analysis stratified by etiological factors indicated that the genotype data was significantly associated with a high risk for patients with alcohol-induced ONFH (P < 0.0001). We found that the IVS7 + 117 A > G polymorphism of the SREBF1 gene is associated with an increased risk of ONFH in the Korean population.

Osteogenic abilities of bone marrow stromal cells are not defective in patients with osteonecrosis

We investigated whether the proliferation activities and osteogenic capacities of bone marrow stromal cells (BMSCs) are depressed in patients with osteonecrosis of the femoral head (ONFH). BMSCs were isolated from fresh bone marrow of the iliac crests of 54 donors and were differentiated into osteogenic lineage in vitro. The results of 27 consecutive patients with ONFH (16 idiopathic and 11 alcohol-induced) were compared with those of 27 patients with a nonnecrotic hip disorder. The proliferative activities of BMSCs in patients with ONFH were not found to be reduced and their osteogenic capacities (alkaline phosphatase activity and calcium deposition amount) were unaltered during in vitro differentiation. Results from patients with idiopathic or alcohol-induced ONFH were similar to those of matched patients with nonnecrotic disorder. These findings suggest that the osteogenic potentials of BMSCs are not defective in patients with ONFH.

The pathogenesis of the alcohol-induced osteonecrosis and the preventive effect of puerarin

目的 探讨酒精性骨坏死发病机制和葛根素的预防作用.方法分离培养小鼠骨髓基质细胞(MSCs),随机分为3组:A组(酒精组),给予酒精0、0.03、0.09、0.15 mol/L;B组(葛根素组),酒精0.09mol/L和葛根素终浓度为0.01 mg/ml;C组(对照组),无酒精与葛根素.苏丹Ⅲ染色,光镜下脂肪细胞计数;测定细胞内甘油三酯含量、碱性磷酸酶活性和细胞培养液中骨钙素含量.采用完整细胞斑点印迹分子杂交方法检测A组和C组细胞中422(aP2)mRNA和Ⅰ型胶原mRNA的表达.采用RT-PCR技术检测3组细胞中PPARγ mRNA和osteocalcin mRNA的表达.结果酒精处理细胞后21d,MSCs分化为脂肪细胞的数量随酒精作用时间延长及浓度增大而增多;细胞内甘油三酯含量明显增高,ALP活性降低,骨钙素含量显著减少.0.09mol/L酒精作用细胞6 d,A组中422(aP2)mRNA表达含量显著增高,Ⅰ型胶原mRNA表达含量明显降低.B组和C组细胞中PPARγmRNA表达明显低于A组,osteocalcin mRNA表达明显高于A组,而B组与C组间差异无统计学意义(P＞0.05).结论酒精能诱导MSCs大量成脂分化,减少其成骨分化,这可能与酒精性骨坏死的发生机制有关.葛根素能够对抗酒精诱导MSCs成脂分化,可能预防骨坏死。

Decreased Osteogenic Differentiation of Mesenchymal Stem Cells in Alcohol-induced Osteonecrosis

We postulated that osteogenic and adipogenic differentiation ability of the mesenchymal stem cells isolated from the bone marrow could be altered in patients with alcohol-induced osteonecrosis of the femoral head. To examine this hypothesis, we investigated the differentiation ability of the mesenchymal stem cells isolated from the bone marrow from the proximal end of the femur during hip replacements in patients with alcohol-induced osteonecrosis of the femoral head and compared it with the differentiation ability of patients with femoral neck fractures. Marrow was collected from the proximal femurs of 33 patients having hip replacement for either alcohol-induced osteonecrosis of the femoral head or femoral neck fractures. The mesenchymal stem cells were isolated and the culture was expanded from the marrow. The cell populations were compared in terms of the doubling time and the differentiation ability to the osteoblasts and adipocytes. The cells obtained from the patients with alcohol-induced osteonecrosis of the femoral head showed a reduced ability to differentiate the osteogenic lineages compared with the cells obtained from the patients with femoral neck fractures. Such changes may play a role in the development of alcohol-induced osteonecrosis of the femoral head. The altered function of mesenchymal stem cells can be responsible for the pathogenesis of osteonecrosis.

The Risk Factors Associated with Alcohol-induced Osteonecrosis of the Femoral Head

Purpose: To assess the relationship between the osteonecrosis of the femoral head (ONFH) and the patterns of alcohol intake and evaluate the risk factors associated with alcohol-induced ONFH using an epidemiologic study. Materials and Methods: The study examined 250 patients (333 hips) with ONFH, who were diagnosed based on the findings after a total hip arthroplasty. Among them, 169 patients who were not associated with the specific etiologic factors except for a history of alcohol were selected in the case group. These patients were compared with the 338 controls, which were matched for gender, age, occupation and education. The patterns of alcohol intake, cigarette smoking, the level of the liver function test and body mass index were statistically assessed in relation to the development of NFH. Results: The incidence of alcohol-induced ONFH was 42.8% in all ONFH patients. The average duration of alcohol ingestion was 8.1 years. The average quantity of alcohol per day, per week and drink-years were 84.8 g, 328.6 g and 4,330 respectively. The elevated relative odds were observed for 1) frequent drinkers (>4/week), 2) the amount of intake per day >90 g, 3) the amount of alcohol intake per week >300 g, 4) drink-year >6,000, 5) the patients had not consumed food with their drinks. A increased risk was found for smokers (>20 cigarettes/day), patients with an increased serum transaminase level and body mass index 25. Conclusion: Chronic alcohol intake showed significant dose-response relation in the development of ONFH. The Increased amount of alcohol per day was a more significant risk factor than the total duration of alcohol intake. The pattern of alcohol consumption is one of the risk factors associated with the development of alcohol induced ONFH.

Incidence and Pathogenesis of Alcohol-Induced Osteonecrosis of the Femoral Head

Anteroposterior pelvic roentgenograms of 790 patients admitted for treatment of alcoholism were examined for evidence of osteonecrosis of the femoral head. Laboratory data on these patients, obtained shortly after admission, demonstrated that average serum cholesterol levels were within normal limits and average serum triglyceride levels were moderately elevated only in those individuals classified as having a severe addition to alcohol. Non-juxta-articular radiographic abnormalities of the femoral head, neck and shaft were common but no changes were observed which were considered to be early indications of structural insufficiency. Two patients had advanced idiopathic bilateral osteonecrosis of the femoral head. One of these patients had undergone one total hip replacement prior to his current admission. This study indicates that there is a very low incidence of osteonecrosis among alcoholics (less than 0.3%). However, alcoholism may lead to osteonecrosis in certain predisposed individuals. A combination of several factors such as systemic fat embolism, elevated circulating levels of inflammatory fatty acids or prostaglandins, and osteoporosis and Charcot-like effects, which are also associated with corticosteroid-induced osteonecrosis, seem to be involved and may contribute, as well, to other instances of femoral head osteonecrosis.