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Background and Purpose: Prevention of osteonecrosis after corticosteroid administration would be important. We examined the potential of vitamin E (alpha-tocopherol) to reduce the incidence of corticosteroid-induced osteonecrosis in an animal model., Methods: Japanese white rabbits were divided into 2 groups; the control group was fed a normal diet and the experimental group was fed alpha-tocopherol-supplemented diet in which alpha-tocopherol (600 mg/kg diet) was added to the normal diet. To induce osteonecrosis, high-dose methylprednisolone acetate (MPSL) (20 mg/kg body weight) was injected once into the right gluteus medius muscle of all rabbits. 4 weeks after the injection of MPSL, the presence or absence of osteonecrosis of bilateral femurs was examined histopathologically. The tocopherol/cholesterol ratios were calculated. The plasma levels of thiobarbituric acid-reactive substances (TBARS) were measured., Results: Alpha-tocopherol-supplemented diet reduced the incidence of osteonecrosis, which developed in 14 of 20 rabbits in the control group and 5 of 21 rabbits in the experimental group (p = 0.004). The tocopherol/cholesterol ratio was higher in the experimental group than in the control group after the alpha-tocopherol administration. The plasma TBARS level was lower in the experimental group than in the control group at 4 weeks after the MPSL administration., Interpretation: Our findings may offer a new approach for the prevention of corticosteroid-induced osteonecrosis.

Background and Purpose: It has been suggested that avascular osteonecrosis (AVN) of the femoral head develops early after renal transplantation. We evaluated the relationship between risk of AVN and dose of steroids administered in different time periods., Methods: Development of AVN was determined using MRI at 3-6 weeks, 9-12 weeks, 24 weeks, and 12 months after transplantation in 150 patients (96 males). We investigated possible associations between acute rejection reactions, the dose of cyclosporine, tacrolimus use, total steroid dose by the second, fourth, sixth, or eighth weeks after transplantation, and incidence of AVN., Results: There was no statistically significant difference between incidence of AVN and presence or absence of an acute rejection reaction. We found a statistically significant association between AVN incidence and the total dose of steroids administered during the first 2 months after transplantation, and there was a doseresponse relationship. No other statistically significant associations were found., Interpretation: Our findings confirm that the total dose of steroids given within the first 2 months after renal transplantation has a great influence on the incidence of AVN.

Steroid-induced osteonecrosis of the femoral head (steroid-induced ONF) is an aseptic and ischemic disease developing after steroid therapy. Functions of hip joint are markedly disturbed when collapse is developed on the femoral head. Steroid-induced ONF accounted for the majority of the ONF. The occurrence mechanism is unknown, and prevention methods and fundamental remedies remain to be established. The timing of the occurrence of steroid-induced ONF is within several months after steroid administration. During the continuous steroid administration, no expansion of necrotic area was found. Recurrence was not also noticed. Patients have no symptoms when steroid-induced ONF occurs due to the establishment of ischemic conditions, and pain appears when the collapse of femoral head develops. There is an interval of several months or years between the occurrence of ONF and the onset of symptoms. Generally, conservative treatment is chosen during the asymptomatic period, and surgical treatment is considered after the symptoms appear. Appropriate screening and early detection are important to rational remedy for steroid-induced ONF.

Idiopathic osteonecrosis of the femoral head (ION) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of corticosteroid-induced ION is unclear, although abnormalities in the coagulation and fibrinolytic systems or in the lipid metabolism have been reported to be involved. We found the differences of gene polymorphism frequencies of ATP-binding casette, sub-family B, member 1 (ABCB1) C3435T, Apolipoprotein B (ApoB) C7623T and cAMP-response element binding protein-binding protein (CBP) (rs3751845) between ION cases and referent patients among those who were subjected to renal transplantation. For the prediction of ION, it is useful to analyze ABCB1 C3435T, ApoB C7623T and CBP (rs3751845) before the administration of steroids.

Background: Nontraumatic osteonecrosis of the femoral head (ONFH) is caused by disruption of blood flow. This disease often occurs in association with steroid treatment. The pathology of steroid-induced ONFH remains unclear, although abnormalities in lipid metabolism have been reported to be involved. In this study, we examined the differences of gene polymorphism frequencies of apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1), which are important proteins for lipid transport, as well as of lipid parameters, between ONFH cases and referent patients among those who were subjected to renal transplantation., Methods: Subjects were 158 cases who had undergone renal transplant, including 34 cases that were diagnosed as ONFH after renal transplantation and 124 cases that were not. Four single nucleotide polymorphisms including C7623T and G12619A for the ApoB gene and G75A and C83T for the ApoA1 gene were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Taqman real-time PCR chemistry. Also, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), ApoB, and ApoA1 were measured. Their relationship to ONFH was statistically evaluated., Results: A higher frequency of 7623TT or CT of the ApoB gene was observed in ONFH cases than in referent patients (P = 0.033), resulting in an elevated odds ratio that was statistically significant (adjusted odds ratio = 6.37, 95% CI = 1.53-26.5, P = 0.011). No significant relationship was observed between other genes and ONFH. Regarding lipid parameters, a higher value of ApoB/ApoA1 ratio was observed in cases (P = 0.045)., Conclusion: For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.

Objective: Osteonecrosis of the femoral head (ONF) is a necrosis due to disruption of the blood flow. The disease often occurs in association with corticosteroid treatment. The pathology of corticosteroid-induced ONF is unclear, although abnormalities in the coagulation and fibrinolytic systems or in the lipid metabolism have been reported to be involved. We examined the relationships between development of ONF and genetic variations and plasma level of lipoprotein(a) (Lp(a)), which is closely involved in the coagulation and fibrinolytic systems and lipid metabolism., Methods: The study population consisted of 112 renal transplant patients undergoing corticosteroid treatment. Their apolipoprotein (a) [apo(a)] isoform was determined by Western blotting, and patients were classified into low molecular weight (LMW) or high molecular weight (HMW) groups. The plasma Lp(a) level was measured. Patients were also examined for 3 single-nucleotide polymorphisms (SNP), -773 (G/A), +93 (C/T), and +121 (G/A). Relationships between these 3 genetic factors of Lp(a) and ONF development were examined using statistical methods including multivariate analysis., Results: A strong relationship was observed between the apo(a) molecular weight phenotype and ONF development, with an increased risk of ONF development for the LMW group (adjusted odds ratio 5.75, 95% CI 1.76-18.74, p = 0.0038). No significant relationships were observed between ONF and plasma Lp(a) level and SNP., Conclusion: Apo(a) molecular weight phenotype would be a useful predictor of ONF that develops after corticosteroid treatment.

Nontraumatic osteonecrosis (ON) of the femoral head is known to be one of the major complications after organ transplantations. Although the precise mechanism is still uncertain, the administration of glucocorticoid (GC) has been considered to play an important role in the occurrence of ON. To elucidate the genetic factors involved in this pathogenesis, we analyzed single nucleotide polymorphisms (SNP) in the genes for the GC receptor (GR), CYP3A4, cAMP-responsive element binding protein-binding protein (CBP), and nuclear receptor co-activator 2 (NCoA2). Among the patients examined, A/G alleles of the CBP gene were demonstrated in 32.4% of those with ON, but in only 14.6% of those without ON (P = 0.018). No relationships were observed between the SNPs of GR, CYP3A4, and NCoA2 genes and the occurrence of ON. These results indicate that the genetic polymorphism of the CBP, which is one of the essential factors exerting the biological effects of GC, may affect susceptibility to steroid-induced ON in patients after renal transplantation. [ABSTRACT FROM AUTHOR]