Incidence Of Osteonecrosis Of The Femoral Head Research Articles

The small screw-apex distance is potentially associated with femoral head osteonecrosis in adults with femoral neck fractures treated by closed reduction and percutaneous 3 parallel cannulated screws

ObjectiveFemoral neck fractures (FNFs) are among the most common fractures in elderly individuals. Surgery is the main treatment for FNFs, and osteonecrosis of the femoral head (ONFH) is one of the unacceptable complications. This study aimed to assess both the clinical and radiological outcomes in patients with FNFs treated with three parallel cannulated screws and to identify relationship between screws position and ONFH.Patients and methodsA total of 100 patients who were treated with closed reduction and fixed with 3 parallel cannulated screws met the inclusion criteria between January 2014 and December 2020 at authors’ institution. The follow-up duration, age, sex, affected side, and injury-to-surgery interval were collected; the neck-shaft angle of both hips, screw-apex distance (SAD) and the tip-apex distance (TAD)were measured; and the Garden classification, quality of reduction and presence of ONFH were evaluated.ResultsThe sample consisted of 37 males and 63 females, with 60 left and 40 right hips affected. The mean age of patients was 54.93 ± 12.24 years, and the mean follow-up was 56.3 ± 13.38 months. The overall incidence of ONFH was 13%. No significant difference was observed in the incidence of ONFH by affected side, age, fracture displacement, injury-to-surgery interval, neck-shaft angle deviation, or reduction quality. The SAD was significantly shorter in ONFH patients than in normal patients for all three screws (p = 0.02, 0.02, and 0.01, respectively).ConclusionsThe short SAD of all screws is associated with femoral head necrosis of FNFs treated with 3 cannulated screws. The short SAD indicated that screws malpositioning in the weight-bearing area of the femoral head, potentially harming the blood supply and compromising the anchorage of the primary compressive trabeculae in this region.

Analysis of incidence and clinical characteristics of osteonecrosis of femoral head in patients with systemic lupus erythematosus treated with glucocorticoid: A descriptive study based on a prospective cohort

To describe the disease characteristics of osteonecrosis of the femoral head (ONFH) in patients with systemic lupus erythematosus (SLE) who experiencing prolonged glucocorticoid (GC) exposure. Between January 2016 and June 2019, 449 SLE patients meeting the criteria were recruited from multiple centers. Hip MRI examinations were performed during screening and regular follow-up to determine the occurrence of ONFH. The cohort was divided into ONFH and non-ONFH groups, and the differences in demographic baseline characteristics, general clinical characteristics, GC medication information, combined medication, and hip clinical features were compared and comprehensively described. The age at SLE diagnosis was 29.8 (23.2, 40.9) years, with 93.1% (418 cases) being female. The duration of GC exposure was 5.3 (2.0, 10.5) years, and the cumulative incidence of SLE-ONFH was 9.1%. Significant differences ( P<0.05) between ONFH and non-ONFH groups were observed in the following clinical characteristics: ① Demographic baseline characteristics: ONFH group had a higher proportion of patients with body mass index (BMI)<20 kg/m 2 compared to non-ONFH group. ② General clinical characteristics: ONFH group showed a higher proportion of patients with cutaneous and renal manifestations, positive antiphospholipid antibodies (aPLs) and anticardiolipin antibodies, severe SLE patients [baseline SLE Disease Activity Index 2000 (SLEDAI-2K) score ≥15], and secondary hypertension. Fasting blood glucose in ONFH group was also higher. ③ GC medication information: ONFH group had higher initial intravenous GC exposure rates, duration, cumulative doses, higher cumulative GC doses in the first month and the first 3 months, higher average daily doses in the first 3 months, and higher proportions of average daily doses ≥15.0 mg/d and ≥30.0 mg/d, as well as higher full-course average daily doses and proportion of full-course daily doses ≥30.0 mg/d compared to non-ONFH group. ④ Combined medications: ONFH group had a significantly higher rate of antiplatelet drug use than non-ONFH group. ⑤ Hip clinical features: ONFH group had a higher proportion of hip discomfort or pain and a higher incidence of hip joint effusion before MRI screening than non-ONFH group. The incidence of ONFH after GC exposure in China's SLE population remains high (9.1%), with short-term (first 3 months), medium-to-high dose (average daily dose ≥15 mg/d) GC being closely associated with ONFH. Severe SLE, low BMI, certain clinical phenotypes, positive aPLs, and secondary hypertension may also be related to ONFH.

Risk factors for osteonecrosis of femoral head after femoral neck fracture fixation with femoral neck system

To explore the risk factors for osteonecrosis of the femoral head (ONFH) after treatment of femoral neck fractures with femoral neck system (FNS). Between January 2020 and February 2021, 179 patients (182 hips) with femoral neck fractures treated by FNS fixation were selected for retrospective analysis. There were 96 males and 83 females with an average age of 53.7 years (range, 20-59 years). There were 106 cases of low-energy-induced injury and 73 cases of high-energy-induced injury. The fractures were classified as type Ⅱ in 40 hips, type Ⅲ in 78 hips, and type Ⅳ in 64 hips according to Garden classification standard, and as typeⅠin 23 hips, type Ⅱ in 66 hips, and type Ⅲ in 93 hips according to Pauwels classification standard. There were 21 patients with diabetes. Patients were divided into ONFH group and non-ONFH group according to whether ONFH occurred at last follow-up. The data of the patients were collected, including age, gender, body mass index (BMI), trauma mechanism, bone mineral density, having diabetes or not, Garden classification and Pauwels classification of fractures, fracture reduction quality, femoral head retroversion angle, and removal of internal fixator or not. The above factors were analyzed by univariate analysis, and then multivariate logistic regression analysis was used to identify risk factors. Total 179 patients (182 hips) were followed up 20-34 months (mean, 26.5 months). Of these, 30 cases (30 hips) developed ONFH at 9-30 months after operation (ONFH group), and the incidence of ONFH was 16.48%. And 149 cases (152 hips) had no ONFH at last follow-up (non-ONFH group). The univariate analysis showed that there were significant differences between groups in bone mineral density, having diabetes or not, Garden classification, femoral head retroversion angle, and fracture reduction quality ( P<0.05). The multivariate logistic regression analysis showed that the Garden type Ⅳ fracture, reduction quality of grading Ⅲ, femoral head retroversion angle >15°, complicated with diabetes were the risk factors for ONFH after FNS fixation ( P<0.05). For the patients with Garden type Ⅳ fracture, poor quality of fracture reduction, femoral head retroversion angle >15°, and diabetes, the risk of ONFH after FNS fixation increases.

Dynamic Hip Screw versus Cannulated Cancellous Screw in Pauwels Type II or Type III Femoral Neck Fracture: A Systematic Review and Meta-Analysis.

Vertically oriented femoral neck fractures (FNFs) are known to be especially unstable FNFs, and they have a higher associated risk of failure. The dynamic hip screw (DHS) technique and the cannulated cancellous screw (CCS) technique are the two main fixation techniques used in the treatment of FNFs. However, no large clinical study has compared the DHS and CCS techniques in patients with high-shear-angle FNFs. MEDLINE, Embase, Cochrane Library, and Web of Science were systematically searched for studies that compared the DHS and CCS techniques for the treatment of Pauwels type II or type III FNF. Pooled analysis was performed to identify differences between the DHS and CCS techniques in Pauwels type II or type III FNF, with a focus on postoperative complications such as fracture nonunion and osteonecrosis of the femoral head (ONFH). We included five studies with a total of 252 patients. The DHS technique was used in 96 patients (DHS group), and the CCS technique was used in 156 patients (CCS group). The pooled analysis revealed that the nonunion rate in the CCS group was significantly higher than that in the DHS group (OR = 0.32; 95% CI, 0.11–0.96; p = 0.04, I2 = 0%), but there was no difference in the incidence of ONFH between the groups (OR = 0.98; 95% CI, 0.20–4.73; p = 0.98, I2 = 53%). For vertically oriented FNFs, the DHS technique is more favorable and has a lower risk of fracture nonunion than the CCS technique.

The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial

BackgroundAn effective prevention strategy for osteonecrosis of the femoral head (ONFH) has yet to be established. We previously reported that the innate immune system via the toll-like receptor (TLR) response induced by corticosteroids leads to the development of ONFH and that repression of IRF7 activity by an inhibitor could interfere with the development of ONFH while maintaining the therapeutic effect of the corticosteroids.ObjectiveIn the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. Furthermore, we conducted a preliminary clinical trial to prevent corticosteroid-induced ONFH in autoimmune disease patients.MethodsMale Wistar rats were randomly divided into four groups. On Day 1, each rat was injected with TLR4 ligand (LPS) or TLR7 ligand (imiquimod), followed by methylprednisolone with or without lansoprazole on Day 2. They were killed at 1 or 14 days after the last injection.We prospectively recruited 30 patients requiring primary high-dose corticosteroid treatment for immune diseases. All patients were administered lansoprazole, starting the night before corticosteroid treatment began. MRI was performed before corticosteroid treatment, and at 4, 12 and 24 weeks afterward.ResultsIn rats, co-treatment of lansoprazole with corticosteroids significantly repressed both IRF7 activity and the development of ONFH. Moreover, in the human patients, the incidence of ONFH was significantly decreased from 53.4 to 13.3%.ConclusionsAlthough the present study is preliminary, the results show that co-treatment of lansoprazole with corticosteroids prevents ONFH development. Lansoprazole may be both safe and effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment.

Transitional changes in the incidence of hip osteonecrosis among renal transplant recipients

BackgroundImmunosuppressive therapy for renal allograft recipients has changed substantially since the introduction of the anti-CD25 monoclonal antibody, basiliximab. We hypothesized that recent improvements in immunosuppressive treatment may reduce the incidence of osteonecrosis of the femoral head (ONFH). This study aimed to investigate transitional changes in the incidence of OFNH among renal transplant recipients by MRI. MethodsParticipants comprised 110 patients who had undergone renal transplantation from 2003 to 2012, during which time basiliximab was in regular use at our institute (Recent group), and 232 patients who had undergone RT between 1986 and 2003 (Past group). We compared ONFH incidence between the two groups and evaluated risk factors for ONFH, including immunosuppressants (calcineurin inhibitors, basiliximab, and/or steroids) and postoperative renal function. ResultsIncidence of ONFH was lower in the Recent group (0%) than in the Past group (3.4%; p = 0.043). In the Recent group, age was greater, ABO/human leukocyte antigen incompatibility was worse, while steroid dose was decreased and post-transplant renal function was improved. Cumulative methylprednisolone dose at postoperative week 2 and delayed graft function were identified as risk factors for ONFH. ConclusionRisk of ONFH after renal transplantation has fallen with the advent of regular use of basiliximab, although this agent does not appear to be a factor directly associated with the incidence of ONFH. Study designClinical prognostic study (Level III case control study).

Clinical study for preoperative traction on impact of osteonecrosis of femoral head in patients with femoral neck fractures

To explore the impact of preoperative traction on the osteonecrosis of the femoral head (ONFH) in patients with femoral neck fractures. Between February 2013 and May 2016, 120 patients with femoral neck fractures, who were treated with screw fixation, were collected. Sixty patients with fractures of Garden type Ⅰ and Ⅱ were non-displaced fracture group; 60 cases with fractures of Garden type Ⅲ and Ⅳ were displaced fracture group. The patients in 2 groups were randomly divided into traction and non-traction subgroups ( n=30). There was no significant difference in gender, age, injury mechanism, damage side, the time from injury to operation, and fracture classification between 2 subgroups ( P>0.05). Intracapsular pressure was recorded before operation. The quality of fracture reduction and the satisfaction ratio of screw implant were evaluated during operation. Visual analogue scale (VAS), Harris score, joint mobility, and the incidence of ONFH would be evaluated at 6 months, 1 year, and 2 years after operation. All incisions of 2 groups healed by first intention after operation. There was no infection or deep vein thrombosis of lower extremity. All patients were followed up 2 years. In displaced and non-displaced fracture groups, the intracapsular pressure of traction subgroups were higher than that of non-traction group ( P<0.05); the differences of the quality of fracture reduction and the satisfaction ratio of screw implant were not significant ( P>0.05) between 2 subgroups. At 6 months, 1 year, and 2 years after operation, VAS scores were higher in traction subgroup than in non-traction subgroup ( P<0.05); and the joint mobility and Harris scores were lower in traction subgroup than in non-traction subgroup ( P<0.05). X-ray films showed all fractures healed. Except for the non-displaced group at 6 months, the incidences of ONFH were higher in traction subgroup than in non-traction subgroup at other time points ( P< 0.05). Preoperative traction may increase the risk of ONFH, which can increase the intracapsular pressure and affect the blood supply of femoral head.

Development of non-traumatic osteonecrosis of the femoral head requires toll-like receptor 7 and 9 stimulations and is boosted by repression on nuclear factor kappa B in rats

Non-traumatic osteonecrosis of the femoral head (ONFH) often occurs after corticosteroid therapy in patients with inflammatory diseases. Recent studies suggest that toll-like receptor (TLR) signaling may contribute to the pathogenesis of inflammatory diseases, and that the reason for corticosteroid therapy for inflammatory diseases is related to the anti-inflammatory activities of corticosteroids through the reduction of NF-κB. We hypothesized that the administration of TLR ligands in combination with corticosteroid causes ONFH and that transcription factors may contribute to the pathogenesis of ONFH. The aim of the study was to evaluate (1) the incidence of ONFH in rats after the administration of TLR7 or TLR9 ligands together with methylprednisolone (MPSL) and (2) whether transcription factors contribute to the development of ONFH. Male Wistar rats (n=148) were divided into five groups as follows: Group 1: Saline+MPSL, Group 2: Imiquimod+Saline, Group 3: Imiquimod+MPSL, Group 4: CpG-C+MPSL, Group 5: Imiquimod+BAY11-7082+MPSL. As a result, ONFH was observed in 0 of 12 rats in Group 1, in 1 of 10 in Group 2, in 6 of 12 in Group 3, in 4 of 12 in Group 4, in 0 of 9 in Group 5. MPSL treatment did not significantly affect IRF7 activity, whereas NF-κB activity was significantly repressed in Group 2 and Group 3. Furthermore, the repression in interferon regulatory factor 7 (IRF7) activity by BAY11-7082 interfered with the development of ONFH simultaneously with the MPSL treatment-induced repression in NF-κB activity. In conclusion, in the present study, corticosteroid treatment after the administration of TLR7 or TLR9 ligands caused ONFH. Repression in NF-κB activity by corticosteroid treatment boosted the development of ONFH.

The influence of age, gender and treatment with steroids on the incidence of osteonecrosis of the femoral head during the management of severe acute respiratory syndrome

Corticosteroid use has been implicated in the development of osteonecrosis of the femoral head (ONFH). The exact mechanism and predisposing factors such as age, gender, dosage, type and combination of steroid treatment remain controversial. Between March and July 2003, a total of 539 patients with severe acute respiratory syndrome (SARS) were treated with five different types of steroid. There were 129 men (24%) and 410 women (76%) with a mean age of 33.7 years (21 to 59). Routine screening was undertaken with radiographs, MRI and/or CT to determine the incidence of ONFH. Of the 129 male patients with SARS, 51 (39.5%) were diagnosed as suffering from ONFH, compared with only 79 of 410 female patients (19.3%). The incidence of ONFH in the patients aged between 20 and 49 years was much higher than that of the group aged between 50 and 59 years (25.9% (127 of 491) versus 6.3% (3 of 48); p = 0.018). The incidence of ONFH in patients receiving one type of steroid was 12.5% (21 of 168), which was much lower than patients receiving two different types (28.6%; 96 of 336) or three different types of steroid (37.1%; 13 of 35).

Inhibiton of IRF7 prevents developing corticosteroid‐induced osteonecrosis of the femoral head

ObjectivesWe previously reported that corticosteroid induced osteonecrosis of the femoral head (ONFH) occurs under activation of NF‐ƒÈB and IRF7 by TLR ligand administration, followed by reduction of NF‐ƒÈB activation after corticosteroid treatment. In the present study, we proved that the reduction of IRF7 activity by an IkB kinase inhibitor prevents ONFH.MethodsMale Wistar rats (n=66) were randomly divided into two groups. Each group rats were given ligands of TLR7 on day 1 and methylprednisolone with or without an IkB kinase inhibitor on day 2. Animals were sacrificed 1 or 14 days after last injection. Histopathological and biochemical analyses were then performed.ResultsThe incidence of ONFH was decreased dose dependently by the IkB kinase inhibitor. The activity of IRF7 was significantly decreased after IkB kinase inhibitor administration, but the activity of NF‐kB did not changed.ConclusionsThe present study shows that inhibition of IRF7 activity by the kinase inhibitor prevents ONFH.

Incidence of osteonecrosis of the femoral head in divers: an epidemiologic analysis in Dalian

Objective To investigate the incidence of osteonecrosis of the femoral head (ONFH) in divers of Dalian.Methods From January 2010 to December 2010,all registered 855 divers in Dalian were enrolled in this study.All divers underwent a unified medical examination and a questionnaire including height,weight,blood pressure and hip inspection.Radiological examination (anteroposterior and frog position)was used for all divers.Suspicious persons with hip pain but normal X-ray performance were confirmed by MRI.Results Sixty-eight divers were confirmed as ONFH,and the incidence of ONFH in divers of Dalian was 7.95％.According to the Ficat classification,12 patients (12 hips) were in Phase 1,40 patients (47 hips)in phase Ⅱ,3 patients (3 hips) in phase Ⅲ,13 patients (15 hips) in phase Ⅳ.The mean age of divers was 32.6+5.5 years (range,18-55 years).The onset ages of most patients ranged from 30 years to 50 years,accounted for 83.82％ (57/68).Among all patients,primary school education accounted for 10.58％ (38/359),junior high school education 6.28％ (28/446),high school education 4.26％ (2/47),university education 0 (0/3); seniority less than 5 years accounted for 4.55％ (20/440),6-10 years 9.69％ (28/289),11-15 years 13.04％ (12/92),16-20 years 21.05％ (4/19),more than 20 years 26.67％ (4/15); self-employed accounted for 11.88％ (19/160),private enterprise 8.41％ (38/452),and national enterprise 4.53％ (11/243).Conclusion The incidence of ONFH is high in divers of Dalian,which is different in terms of age,seniority,level of education,enterprise nature. Key words: Femur head necrosis; Diving; Incidence; Epidemiologic studies

Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats

Background and purpose Although the definite cause of steroid-induced osteonecrosis of the femoral head (ONFH) is unknown, peripheral circulatory failure, lipid metabolism disturbance, and increased oxidative stress are considered to be possible causes. We investigated whether pravastatin as a statin treatment reduces (1) the incidence of ONFH, (2) the adipocyte area, and (3) bone marrow changes in the femoral head.Methods We divided up 81 thirteen-week-old spontaneously hypertensive stroke-prone (SHRSP)/Izm male rats into 4 groups: a control group (group C), a group given pravastatin (group P), a group given steroid (group S), and a group given both pravastatin and steroid (Group PS). The steroid was administered at 15 weeks of age. Pravastatin, as a statin, was administered in the drinking water for 4 weeks. The rats were killed when 17 weeks old. Osteonecrosis was diagnosed based on histopathological examination. Oxidative stress was assessed from immunostaining.Results The incidence of histological osteonecrosis was lower in the groups given pravastatin. The percentage of adipocyte area in the bone marrow was lower in the PS group than in the S group. Immunohistochemical staining for oxidative stress showed that staining was less in the PS group than in the S group. Pravastatin had no effect on the blood-derived biochemical findings on lipid metabolism. However, it reduced the incidence of steroid-induced ONFH in these SHRSP rats. We presume that this occurred by reducing oxidative stress and by reducing the percentage of adipocyte area in the femoral heads.Interpretation Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH.

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

Risk factor of osteonecrosis of the femoral head in patients with systemic lupus erythematosus

Objective To investigate the risk factor of osteonecrosis of the femoral head (ONFH)in patients with systemic lupus erythematosus (SLE).Methods 376 patients with SLE in our hospital were enrolled in the present study.The retrospective analysis was made to investigate the risk factor of ONFH on the pathological and follow-up data.Results The incidence of ONFH in 376 SLE patients was 7.18%.Oral ulcer,Renault's phenomenon,vasculitis,osteoporosis,TC,TG,accumulated dosage of hormone and hormone intensive therapy were the risk factors of ONFH.Conclusion The incidence of ONFH in patients with SLE is relatively high,and the risk factors include Renault' s phenomenon,vasculitis,osteoporosis,TC,TG and usage of immunosuppresive treatment,especially the hormone intensive therapy with large doses. Key words: Lupus erythematosus; Femur head necrosis; Risk factor

Pentosan Reduces Osteonecrosis of Femoral Head in SHRSP

Increased oxidative stress is considered one of the main causes of steroid-induced osteonecrosis of the femoral head (ONFH). The aim of this study was to evaluate the effects of a steroid hormone and pentosan polysulfate sodium (pentosan), a heparin analog, in stroke-prone spontaneously hypertensive rats (SHRSP) as a model of ONFH. One hundred twenty-three 13-week-old male SHRSP//Izm rats were divided into four groups: a control group (group C), pentosan-administered group (group P), steroid-administered group (group S), and group administered pentosan plus steroid (group PS). Methylprednisolone acetate, as the steroid hormone, at a dose of 4 mg (15 mg//kg) was administered at 15 weeks of age. Pentosan at a dose of 3 mg//day//kg was continuously administered intraperitoneally from 13 weeks of age for 4 weeks. Rats were sacrificed at 17 weeks of age, and heart blood and both femora were collected. Triglyceride levels were significantly lower in group PS than in group S, indicating that pentosan improves lipid metabolism. The incidence of histologic ONFH was significantly lower in group P, at 14.8%% (10//71 femoral heads), than in group C, at 30.4%% (17//56 femoral heads), and significantly lower in group PS, at 40.8%% (29//71 femoral heads), than in group S, at 91.3%% (42//46 femoral heads), indicating that pentosan markedly inhibits ONFH. Immunohistochemical staining for oxidative stress showed that the stainability was significantly lower in group PS than in group S. Pentosan seems to reduce the incidence of ONFH in SHRSP by improving lipid metabolism and decreasing oxidative stress.

Effect of rifampicin on the risk of steroid-induced osteonecrosis of the femoral head

To investigate the effects and possible mechanism of rifampicin on steroid-induced osteonecrosis of the femoral head (ONFH). Bone marrow stromal cells (BMSC) separated from male rats were cultured in vitro without any treatment (Group mA), exposed to dexamethasone (Group mB), treated with rifampicin (Group mC), and exposed to dexamethasone and rifampicin simultaneously (Group mD) respectively (n = 5 in each group). After 7 days, P-glycoprotein (P-gp) activity and adipogenesis of the BMSC were evaluated. In an in vivo experiment, 80 rats were randomly divided into 4 groups (n= 20 in each group). Group A received intragastric saline for 5 weeks. Group B received intragastric saline for one week, followed by subcutaneous methylprednisolone and saline for 4 weeks. Group C received intragastric rifampicin for 5 weeks. Group D received intragastric rifampicin for one week, followed by subcutaneous methylprednisolone and rifampicin for 4 weeks. At the end of the experiment, all rats underwent analysis of P-gp activity of BMSC, P-gp expression in the femoral heads, MRI and histomorphometry of the femoral heads. In vitro, the P-gp activity of BMSC increased and lipid accumulation decreased significantly in Group mD, compared to Group mB. In vivo, P-gp activity and P-gp expression in Group D increased compared to Group B. The mean area of MRI abnormal signal, adipocytic variables and apoptotic cells in Group D decreased, mean percentage of the whole epiphysis made up by the epiphyseal ossification center and trabecular structure variables improved compared to those in Group B. The incidence of ONFH was lower in Group D (50%) than in Group B (80%). Rifampicin may decrease the risk of steroid-induced ONFH by enhancing P-gp activity, thus preventing steroid-induced BMSC adipogenesis.

Relationship between postrenal transplant osteonecrosis of the femoral head and gene polymorphisms related to the coagulation and fibrinolytic systems in Japanese subjects.

Nontraumatic osteonecrosis of the femoral head (ONFH) is one of the complications that may occur after renal transplantation. We investigated the relationship between the incidence of ONFH and polymorphisms in the genes for plasminogen activator inhibitor (PAI)-1, which is one of the major regulatory proteins of the fibrinolytic system, and 5,10-methylenetetrahydrofolate reductase (MTHFR), which is associated with the plasma levels of homocysteine in Japanese subjects. Thirty-one patients with postrenal transplant ONFH and 106 patients without ONFH were selected. Genotypes of PAI-1 4G/5G and MTHFR C677T were determined by direct sequencing of genomic DNA. In addition, plasma PAI-1 antigen (Ag) levels and plasma total homocysteine (tHcy) levels at the steady state were measured. The relationships between the incidence of ONFH and these genotypes, as well as plasma levels of the gene products, were investigated. Plasma PAI-1 Ag levels were the highest in patients with the 4G/4G genotype, and plasma tHcy levels were the highest in patients with TT genotypes of MTHFR C677T. However, the relationship between the incidence of ONFHH and PAI-1 4G/5G or MTHFR C677T was not observed. The relationship between the incidence of ONFH and plasma levels of PAI-1 Ag or tHcy was not observed. Genotypes of PAI-1 4G/5G and MTHFR C677T or plasma concentrations of PAI-1 Ag and tHcy had no effect on the incidence of ONFH in Japanese subjects, unlike the results of studies performed in white subjects. The effect of genetic background on the pathologic conditions that developed in patients with postrenal transplant ONFH may differ according to race.