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This study aimed to evaluate femoral perfusion using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for two weeks after the simultaneous initiation of electrical stimulation (ES) and steroid treatment in a steroid-induced osteonecrosis (ON) model. A single dose of methylprednisolone was injected into 14 rabbits. Seven rabbits underwent ES (ES group), and seven rabbits did not (control group). DCE-MRI was performed before steroid administration and 1, 5, 10, and 14 days after steroid administration. Regions of interest were set in the bilateral proximal femora. The enhancement ratio, initial slope, and area under the curve were analyzed. These parameters were evaluated after steroid administration in each group and between the two groups, and the ratios of ON in both groups were compared. In the control group, the minimum values of all parameters decreased significantly after steroid administration (P < 0.05), but in the ES group, the parameters did not decrease. In the ES group, all parameter values were significantly increased on the 10th and 14th days (P < 0.05). All parameter values in the ES group were significantly higher than those in the control group on the 14th day (P < 0.05). In the control group, ON was detected in three of five rabbits (in three of ten femora). In the ES group, ON was not detected. These results suggest that increased femoral blood flow elicited by ES may be related to ON prevention after steroid administration. [ABSTRACT FROM AUTHOR]

Background and purpose - It has been suggested that avascular osteonecrosis (AVN) of the femoral head occurs early after systemic steroid administration. The purpose of this study was to investigate the risks regarding development of AVN at a very early stage after renal transplantation. Methods - The presence or absence of AVN was determined by MRI at 4 weeks, at 6-12 weeks, at 24 weeks, and at 12 months after renal transplantation in 286 patients (183 males) with a mean age of 39 (16-65) years. The relationship between AVN and age, sex, absence or presence of acute rejection (AR), type of transplanted kidney (living or cadaveric), type of immune suppressor, and total dose of orally administered steroids given in the 2-week period after transplantation was investigated. Results - There were no statistically significant correlations between the development of AVN and age, sex, absence or presence of AR, type of transplanted kidney, or type of immune suppressor. A significant dose-response relationship was found between development of AVN and the total dose of steroid administered in the first 2 weeks after surgery. Interpretation - We found a relationship between AVN development and steroid dose in the early postoperative period, and we also showed a dose-response relationship. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the preoperative errors in the pelvic tilt of 249 hips before total hip arthroplasty using fluoroscopic imaging while the patients were in the lateral decubitus position. The mean absolute value errors of the pelvic tilt were 2.94° (SD, 2.92°), 2.49° (SD, 2.68°), and 5.92° (SD, 5.20°) in the coronal, transverse, and sagittal planes, respectively. Such preoperative errors in the pelvic tilt contribute to malpositioning of the acetabular component, as is frequently observed on postoperative radiographs. We reduced the incidence of malpositioning by correcting the errors in the pelvic tilt through repositioning of the operating table using fluoroscopic imaging before surgery. The new technique using fluoroscopic imaging described in this article can be performed within a short time without a navigation system. [Copyright &y& Elsevier]

Abstract: The clinical results of total hip arthroplasty using the Richards Modular Hip System prosthesis were evaluated in 41 patients (44 joints). The mean Harris hip score improved from 42 points before surgery to 82 after 1 year, 85 at 5 years, and 79 at the final examination. The average polyethylene wear rate was 0.09 ± 0.07 mm/y. Forty joints (90.9%) achieved press fit in either of the proximal or the distal stem portion, and only 4 joints (9.1%) failed to achieve press fit in both the proximal and distal stem portions. Although the 10-year survival of the stem was 94.5% and no revisions of the stem were performed, osteolysis was found at high frequency at a distal stem. The high incidence of osteolysis has been the limiting factor in the long-term success of Richards Modular Hip System. Achievement of good canal fill in both the proximal and distal stem portions did not contribute to the good long-term result of the stem. [Copyright &y& Elsevier]

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 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 α-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5′ UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 × 10−13) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis. [ABSTRACT FROM AUTHOR]

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.

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.

Objectives: To identify whether differences exist in the outcomes between patients undergoing hemodialysis and elderly nonhemodialysis patients with a femoral neck fracture., Design: Retrospective review., Setting: Level 1 trauma center., Patients/interventions: A total of 71 femoral neck fractures in 62 patients undergoing hemodialysis treated nonoperatively or operatively., Main Outcome Measurements: Clinical outcomes were analyzed to identify factors that may be correlated with life expectancy and functional prognosis., Results: The overall survival rates in this study at 1-year and 5-years postfracture were found to be 89.8% and 51.5%, respectively. There were significant correlations among the survival rate, patients' age, type of treatment, prefracture ambulation status, and prefracture activities of daily living status. However, using multivariate analysis, the only significant predictor of life expectancy was prefracture ambulation status. As for functional prognosis, the rates of total ambulation recovery and total activities of daily living recovery at 1-year postfracture were 50.0% and 71.2%, respectively. Both patients' age and age at the onset of hemodialysis may contribute considerably to functional prognosis in patients undergoing hemodialysis after femoral neck fracture., Conclusions: The present study suggests that the clinical outcomes of patients with femoral neck fractures who undergo hemodialysis are considerably superior to those of previous studies. In addition, when those fractures are treated surgically with specific management in patients undergoing hemodialysis, it may be possible to expect a life expectancy and functional prognosis similar to elderly nonhemodialysis patients with hip fractures.

Although epidemiological studies on epiphyseal injury have been reported, such studies have not been made systematically in Japan. In this study, we examined the incidence of epiphyseal injury in paediatric patients treated at five general hospitals and three private clinics. We treated the patients with limb injuries between January 1992 and December 1997, and reviewed them at least 18 months after the original injuries. The original radiograms and the completed case records were classified according to age and sex of the injured children, site of the fracture, type of treatment, and its complications. Epiphyseal injuries accounted for 17.9% of all paediatric fractures. The most frequently injured epiphysis was the phalanges of hands, 21.9% of all physeal injuries. Salter-Harris type I accounted for 28.6% of physeal injuries; type II (60.9%) revealed the largest number of cases in this study, compared with type III (6.7%) and type IV (3.7%). Type V was not recognized. Most physeal injuries were treated conservatively. Either weight-bearing joints or elbow joints were treated surgically. Complications of physeal injuries were seen in seven cases. Five cases involved the upper limb, and the other two cases involve the lower limb. Although deformity or malfunction caused by physeal injuries was remained, only one case needed a corrective osteotomy. Other six cases revealed a fair prognosis.

Limb lengthening by the callotasis method has been clinically applied to patients who suffered from limb length inequality, micromelia, angular deformation and partial bone defect on long bones. However, this technique was time consuming and led to various complications, such as infection at the pin insertion sites, limitation of the range of motion in adjacent joints, muscular weakness and peripheral neuroparalysis. This study was undertaken to investigate whether alternating current electric (AC) stimulation could shorten the maturation period during callotasis. The tibiae of 20 immature male Japanese white rabbits were osteotomized and fixed with external lengthener (Orthofix M100; Orthofix Srl, Bussolengo, Italy). The experimental schedule lasted 5 weeks consisting of 1 week for the latency period, 2 weeks for distraction and 2 weeks for maturation. Twenty rabbits were equally divided into two groups: the control group and the electrical stimulation (ES) group. The control group was not stimulated with an AC stimulator. The ES group was stimulated for 5 weeks just after osteotomy. The obtained results revealed radiologically, electrophysiologically and histologically that AC stimulation accelerated the maturation of lengthened callus and that it could shorten the time course of callus lengthening.

To investigate the usefulness of epiphyseal quotient (EQ) measurement for outcome prediction in patients with Legg-Calve-Perthes disease (LCPD), magnetic resonance (MR) imaging was performed in 26 patients with unilateral LCPD within 6 months of the disease onset and subsequently once every 3 months. All the patients were treated conservatively in our institute between 1990 and 1999. The mean follow-up period was 80 months. Clinical outcome was evaluated based on the plain radiograms of the femoral head at the final examination according to Stulberg's classification: the patients whose outcome was class I were regarded as 'excellent' (excellent group), class II as 'good' (good group), and classes III, IV and V as 'poor' (poor group). The excellent group consisted of 10 patients, the good group of 12, and the poor group of four. The EQ measured on MR images (MR-EQ) decreased remarkably in the poor group chronologically, whereas there was no decrease in the excellent group and a slow decrease in the good group. The mean MR-EQ at or before the sixth month (range, 2-6 months; mean, 4.9 months) was 86.2 (range, 76.8-94.8) in the excellent group, 78.3 (57.0-93.4) in the good group, and 67.4 (57.8-74.5) in the poor group (P<0.05 among the three groups). According to our results, because all patients having an MR-EQ at or before the sixth month of 75 or higher were classified in the excellent or good groups, it is thought that the ongoing method of treatment can be continued. On the other hand, since half of the patients having an MR-EQ at or before the sixth month of lower than 75 were classified in the poor group and had a high potential for a poor outcome, it is thought that these patients require strict containment therapy, and altering the surgical procedure could be considered depending on the particular patient. It was thought that the MR-EQ is a useful predictive factor of LCPD prognosis.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Advances in transplantation technology have brought about great benefits to patients suffering from organ failure, but the problem still remains of complications induced by steroids used for post-transplant immunosuppression. Among the side-effects caused by steroids, non-traumatic osteonecrosis of the femoral head (ONF) constitutes a serious problem. The same protocol for steroid administration induces ONF in some patients, but not in others, indicating the presence of individual difference in steroid sensitivity. We hypothesized that this difference might be mediated by the drug-transport protein, P-glycoprotein (P-gp), and investigated the relationship between single nucleotide polymorphisms in the multidrug resistance gene 1 (ABCB1, MDR1) encoding P-gp and ONF. Subjects comprised 136 patients receiving kidney transplantation. Thirty patients developed post-transplant ONF. Genomic DNA was extracted from peripheral blood, and genotypes of ABCB1 C3435T (exon 26) and G2677T/A (exon 21) were determined by direct sequencing. Multivariate analyses based on clinical information were performed to determine the relationship between ABCB1 genotypes and ONF. The dose/concentration (D/C) ratios of tacrolimus were also determined to estimate the activity of P-gp in patients with different genotypes of ABCB1 C3435T (CC, CT, TT), and in those who did and did not develop ONF. The ABCB1 3435TT genotype showed a significantly lower incidence of ONF (adjusted odds ratio = 0.10, P = 0.034). The D/C ratio in the 3435TT genotype was significantly higher than that in the 3435CC genotype. The D/C ratio in patients developing ONF was significantly higher than in those patients who did not develop ONF. The results suggest increased activity of P-gp in patients with the 3435TT genotype and in those who did not develop ONF. The ABCB1 2677 homozygous variant type also showed a lower incidence of ONF (adjusted odds ratio = 0.26, P = 0.056). The 3435T and 3435C alleles were in linkage disequilibrium with the 2677T and the 2677G alleles, respectively, in the study population. An assessment of C3435T and G2677T/A polymorphisms preceding steroid treatment could be useful for predicting the resistance to ONF development., (Copyright 2003 Lippincott Williams & Wilkins)

Ischemic bone necrosis following talar fractures is a problematic complication and its early diagnosis is important. Patients with Hawkins Type II and III talar fractures received internal fixation using titanium alloy screws, and chronological bone changes were observed with Magnetic Resonance Imaging (MRI). With the Type II patient, Hawkins' sign was radiographically confirmed 2 months after the surgery. Furthermore, there were no changes of MR images for 2 years and a good clinical outcome was obtained. However, in the Type III patient, Hawkins' sign was negative and MRI revealed a low signal-intensity band on the talus 2 months after the surgery and then necrosis was radiographically confirmed; pain appeared 10 months later. These 2 cases suggest that MRI is a useful means for detecting bone necrosis with talar fractures in the early post-operative period.