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PURPOSE To evaluate perfusion during the early phase after steroid administration in vivo using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a high magnetic field MRI system. The main pathogenesis of steroid-induced osteonecrosis is considered to be ischemia. MATERIALS AND METHODS A single dose of methylprednisolone (MPSL) was injected into nine rabbits. DCE-MRI was performed for these rabbits before MPSL administration and 1, 5, 10, and 14 days after administration. Time-signal intensity curves were created for each femur based on the signal intensity to evaluate perfusion. Enhancement ratio (ER), initial slope (IS), and area under the curve (AUC) were calculated and the value before MPSL administration and the minimal value after administration were compared statistically. RESULTS ER, IS, and AUC values after MPSL administration significantly decreased (P < 0.05, P < 0.01, and P < 0.01, respectively). All of them decreased by the 5th day in 56% of the femora and by the 14th day in 83%, and some femora even showed a decrease from the 1st day. CONCLUSION In this study, decreased perfusion in the femora after steroid administration was proven. Additionally, we could show that it occurred from the early days after steroid administration.

The Japanese Orthopaedic Association (JOA) hip score has been widely used in Japan as a method to assess hip joint diseases. The JOA hip score consists of four subcategories: pain (Pain), range of motion (ROM), ability to walk (Gait), and activities of daily life (ADL). We present the first report to verify the reliability and validity of the JOA hip score.A total of 123 patients with osteoarthritis of a unilateral hip and 29 patients with osteonecrosis of a unilateral hip were investigated. The JOA hip score was recorded by orthopedic surgeons in their offices. On the same day, each patient answered a Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) (Japanese version 1.2) by himself or herself. The SF-36 survey measures eight subscales. The internal-consistency reliability of the JOA hip score was evaluated by Cronbach's coefficient alpha. The validity of the JOA hip score was tested by Spearman's correlation coefficients between the four subcategories of the JOA hip score and the eight SF-36 subscales.When patients with osteoarthritis with conservative treatment were assessed by the JOA hip score, Cronbach's coefficient alpha was 0.70, demonstrating internal-consistency reliability. However, when the JOA hip score was used for other groups, Cronbach's coefficient alpha was0.70, demonstrating the lack of internal-consistency reliability. Significant correlations were observed between Pain and bodily pain (r = 0.63), between Gait and physical functioning (PF) (r = 0.70), and between ADL and PF (r = 0.81), but not in any other combinations.We found that the JOA hip score is a reliable system only for patients with osteoarthritis of the hip with conservative treatment. The JOA hip score is a scaling system with convergent and discriminant validity for the assessment of physical function and pain.

Background and purpose Prevention of osteonecrosis after corticosteroid administration would be important. We examined the potential of vitamin E (α-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 α-tocopherol-supplemented diet in which α-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 ra...

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.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.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).For the prediction of ONFH, it is useful to analyze ApoB C7623T and plasma ApoB/ApoA1 ratio before the administration of steroids.

To evaluate perfusion during the early phase after steroid administration in vivo using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a high magnetic field MRI system. The main pathogenesis of steroid-induced osteonecrosis is considered to be ischemia.A single dose of methylprednisolone (MPSL) was injected into nine rabbits. DCE-MRI was performed for these rabbits before MPSL administration and 1, 5, 10, and 14 days after administration. Time-signal intensity curves were created for each femur based on the signal intensity to evaluate perfusion. Enhancement ratio (ER), initial slope (IS), and area under the curve (AUC) were calculated and the value before MPSL administration and the minimal value after administration were compared statistically.ER, IS, and AUC values after MPSL administration significantly decreased (P0.05, P0.01, and P0.01, respectively). All of them decreased by the 5th day in 56% of the femora and by the 14th day in 83%, and some femora even showed a decrease from the 1st day.In this study, decreased perfusion in the femora after steroid administration was proven. Additionally, we could show that it occurred from the early days after steroid administration.

Pulsed electromagnetic field (PEMF) therapy has been widely used in clinical practice for bone fracture healing. However, the mechanism of its action remains to be elucidated. Our object was to investigate the mechanism by which PEMF accelerates bone fracture healing.We used 20 mice in this study. Ten mice received PEMF for 10 h/day for 1 week via the coils of a PEMF stimulation device (PEMF group), while the remaining 10 mice did not (control group). The femurs were harvested immediately after euthanasia to examine the proteins included in the bone marrow. The proteins examined by Western blotting were growth factors with angiogenetic activities, including tunica interna endothelial cell kinase-2, angiopoietin-1, angiopoietin-2, fibroblast growth factor-2, and vascular endothelial growth factor. The expression levels of angiogenesis-related proteins extracted from the bone marrow of each mouse were compared.The expression levels of angiopoietin-2 and fibroblast growth factor-2 were significantly higher in the PEMF group than in the control group. This difference suggests that PEMF may induce an angiogenesis-prone environment in the bone marrow. Such angiogenesis acceleration represents one possible mechanism for the acceleration of bone fracture healing by PEMF. There were no significant differences between the two groups for the expression levels of tunica interna endothelial cell kinase-2, angiopoietin-1, and vascular endothelial growth factor. The lack of increase in tunica interna endothelial cell kinase-2 expression may indicate that PEMF does not unnecessarily increase blood vessels in normal bone marrow. The lack of an increase in the expression level of vascular endothelial growth factor suggests that PEMF does not have invasive effects including the induction of hypoxic conditions and inflammation on the bone marrow.The angiogenesis-promoting function of PEMF may contribute to its mechanism to noninvasively accelerate bone fracture healing.

Osteonecrosis of the femoral head (ONF) often develops following corticosteroid administration. We previously investigated the genetic background for the development of corticosteroid-induced ONF and found relations between ONF development and genetic polymorphisms in the ATP binding cassette B1 (ABCB1) gene (C3435T), apolipoprotein B (ApoB) gene (C7623T), and cAMP-response element binding protein-binding protein (CBP) gene (rs3751845). In the present study, we examined whether combined information regarding these three single nucleotide polymorphisms (SNPs) in the ABCB1, ApoB, and CBP genes is useful for predicting ONF development.A case-control study was performed to study the development of corticosteroid-induced ONF. The cases were 34 patients who developed ONF, and the references were 123 patients who did not develop ONF. To evaluate the presence of interactions among the ABCB1, ApoB, and CBP genes, a synergistic index was calculated using an additive model.The synergistic index between the ABCB1 and CBP genes was1.00 (1.99), revealing the presence of an interaction.Through analysis of multiple genes that may affect ONF development, we have shown a possible relation among genes encoding completely different proteins. We believe that analysis of the interactions among these genes can contribute to elucidating the mechanism of ONF development in addition to enabling identification of high-risk patients for ONF development.

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.