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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]

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. J. Magn. Reson. Imaging 2015;41:935-940. © 2014 Wiley Periodicals, Inc. [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]

Background: Although numerous studies describe the clinical characteristics of idiopathic osteonecrosis of the femoral head (ONFH) in specific study populations, these have not been confirmed in countrywide studies. Questions/purposes: We therefore determined: (1) the annual number of patients seeking medical care and number of patients newly diagnosed; and (2) the distribution of the age and gender of the patients, potential causative factors, severity of the disease, and operative procedures performed. Patients and Methods: We conducted a nationwide epidemiologic survey in 2005. The survey included all orthopaedic departments in Japan by stratified random sampling according to the number of beds. Results: The number of patients who sought medical care for idiopathic ONFH during 2004 was estimated to be 11,400 (95% confidence interval, 10,100–12,800). We obtained clinical information from 1502 of these patients. The peak in age distribution occurred in the 40s. Potential causative factors were systemic steroid administration (51%) and habitual alcohol use (31%). Hip replacement was the most frequently performed procedure (65%). Among patients with a history of systemic steroid administration, systemic lupus erythematosus was reported most frequently (31%) as the underlying disease. Among patients younger than 40 years, steroid use was the most prominent potential causative factor (60%), and hip replacement frequently was performed (45%). A greater proportion of patients with no history of steroid or alcohol use was observed among patients 65 years or older (41%). Conclusions: In addition to the disease burden of idiopathic ONFH in Japan, our results confirmed the importance of developing preventive and treatment strategies, especially among the younger population. Level of Evidence: Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

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]

Aim: The purpose of this study was to investigate risk factors for hip fracture in 169 Japanese elderly women. Methods: Patients were divided into three groups: 53 patients had osteoporosis with hip fractures (FX-G), 59 patients had osteoporosis without hip fractures (NFX-G) and 57 patients had low back pain with neither osteoporosis nor hip fracture (NOP-G). Bone mineral density (BMD) of lumbar spine, bone-specific alkaline phosphatase (BAP) and deoxypyridinoline (DPD) were compared among the three groups. Results: The mean BMD of FX-G and NFX-G was lower than that of NOP-G, but there was no significant difference between FX-G and NFX-G. Although the mean BAP of FX-G was similar to that of NOP-G, both were lower than NFX-G ( P < 0.05). However, the mean DPD of FX-G was higher than the other groups ( P < 0.05, vs NFX-G, P < 0.001, vs NOP-G). The percentage of patients who showed BAP levels less than 35 IU/L and DPD levels of 7.5 nmoL/mmol-Cr or more, was highest in FX-G (72.7%). This percentage was lower for NFX-G (30.9%) and NOP-G (16.4%). The odds ratio of hip fracture occurring was 5.77 (95% confidence interval, 2.25−14.66). Conclusion: Bone turnover consisting of increase in bone resorption and decrease in bone formation apart from BMD of lumbar spine resulted in a higher incidence of hip fracture for Japanese elderly women with osteoporosis. [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]

Establishing a means to prevent osteonecrosis after corticosteroid administration is an important theme. We asked whether pulsed electromagnetic field stimulation, a noninvasive treatment, could prevent osteonecrosis. Ninety rabbits were divided into four treatment groups: (1) exposure of 10 hours per day to electromagnetic stimulation for 1 week, followed by injection of methylprednisolone (20 mg/kg), and exposure of 10 hours per day to electromagnetism for a further 4 weeks (n = 40); (2) methylprednisolone injection only (n = 40); (3) no treatment (n = 5); and (4) exposure of 10 hours per day to electromagnetism for 5 weeks (n = 5). After 5 weeks, we harvested and histologically examined femurs bilaterally. The frequency of osteonecrosis was lower in the steroid-electromagnetism group (15/40) than in the steroid-only group (26/40). No necrotic lesions were found in the two control groups. We observed no clear effects of electromagnetism on the number, location, extent, and repair of necrotic lesions and intramedullary fat cell size in affected rabbits. Pulsed electromagnetic field stimulation reportedly augments angiogenesis factors and dilates blood vessels; these effects may lower the frequency of osteonecrosis. Exposure to pulsed electromagnetic field stimulation before corticosteroid administration could be an effective means to reduce the risk of osteonecrosis. [ABSTRACT FROM AUTHOR]

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]

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]

Objective: The femoral head is reported to be in a markedly hypoemic state as compared with other tissues even under normal conditions, and it is therefore necessary to understand its hemodynamics to investigate the pathogenesis of hip disorders. It is known that aspects of intraosseous hemodynamics including blood flow and blood pool can be evaluated soon after radioisotope administration. In this study, hemodynamic changes in the femoral head according to gender and age were examined by investigating accumulation of radioisotope in the tissue during the early phase of bone scintigraphy.Methods: The subjects of this study consisted of 58 joints of 31 men and 75 joints of 41 women, whose ages ranged from 15 to 87 years (average age: 67.9 years). Images of bone scintigraphy were obtained for 15 to 20 minutes at 5 minutes and at 3 hours after radioisotope administration. The ratio of accumulation in the femoral head to that in the diaphysis (head-to-diaphysis ratio, HD ratio) was calculated.Results: HD ratios obtained 15-20 minutes later ranged from 0.01 to 7.35 (1.88 +/- 0.91, mean +/- SD). HD ratios decreased with age, and a significant inverse correlation was observed between age and HD ratio, demonstrating a correlation coefficient of -0.27 (p = 0.001). The HD ratio among men was 0.01-3.57 (1.66 +/- 0.71), while that among women was 0.53-7.35 (2.05 +/- 1.01), and a significant difference was observed in HD ratio between men and women (p = 0.02). There was a significant difference in HD ratios between men and women in their teens to forties (p = 0.03), while no significant differences was observed in the other age groups.. HD ratios obtained 3 hours later ranged from 0.44 to 6.32 (1.95 +/- 0.79, mean +/- SD), and no significant correlation was observed between age and HD ratio, demonstrating a correlation coefficient of -0.14.Conclusion: The present study demonstrated that blood flow and blood pool of the femoral head decrease with aging particularly in women. This hemodynamic deterioration of the femoral head caused by aging may have an effect on the onset and progression of hip disorders by influencing bone metabolism. [ABSTRACT FROM AUTHOR]

Objective: Non-traumatic osteonecrosis of the femoral head (ONF) is considered to be a disease that occurs primarily due to ischemia of the femoral head, while its etiology and pathology are not fully understood. It is therefore necessary to identify the characteristics of the hemodynamics of the femoral head. In this study, the hemodynamics in the ilium and proximal regions of the femur, including the femoral head, was investigated using positron emission tomography (PET).Methods: The subjects of this study consisted of 8 hip joints of four healthy male adults and 3 hip joints on the contralateral side of a femoral neck fracture, avulsion fracture of the greater trochanter and coxarthrosis (1 case each, all females) for a total of 11 hip joints of 7 subjects. The ages of the subjects ranged from 25 to 87 years (average age: 54 years). Blood flow was measured by means of the H215O dynamic study method and blood volume was measured by means of the 15O-labeled carbon monoxide bolus inhalation method.Results: Blood flow was determined to be 9.1 +/- 4.8 ml/min/100 g in the ilium and among proximal regions of the femur (femoral head, neck and intertrochanteric region), 1.8 +/- 0.7 ml/min/100 g in the femoral head, 2.1 +/- 0.6 ml/min/100 g in the femoral neck, and 2.6 +/- 0.7 ml/min/100 g in the intertrochanteric region. In addition, blood volume was 4.7 +/- 1.3 ml/100 g in the ilium, and among proximal regions of the femur, 1.1 +/- 0.5 ml/100 g in the femoral head, 2.1 +/- 0.7 ml/100 g in the femoral neck, and 2.6 +/- 0.9 ml/100 g in the intertrochanteric region. The results showed that both blood flow and volume were lowest in the femoral head. Blood flow and volume were significantly lower in the proximal regions of the femur (femoral head, neck and intertrochanteric region) than in the ilium (p < 0.01).Conclusion: The present study demonstrated that the femoral head is in a hypoemic state as compared with other osseous tissue, indicating that even the slightest exacerbation of hemodynamics in the femoral head can trigger an ischemic condition culminating in ONF. [ABSTRACT FROM AUTHOR]

Objective: To deepen understanding of hemodynamics in the femoral head, i.e., the essential factor in clarifying pathogenesis of hip disorders, this study examined blood flow and blood volume in the femoral heads of healthy adults, and their changes with age, by using positron emission tomography (PET).Methods: In 16 healthy adult males (age: 20-78 years old, mean age: 42 years), blood flow was measured by means of the H2(15)O dynamic study method, and blood volume was measured by means of the (15)O-labeled carbon monoxide bolus inhalation method.Results: Blood flow was 1.68-6.47 ml/min/100 g (mean +/- SD: 3.52 +/- 1.2), and blood volume was 1.67-6.03 ml/100 g (mean +/- SD: 3.00 +/- 1.27). Blood flow significantly decreased (p < 0.01) with age, and blood volume significantly increased (p < 0.05).Conclusion: PET was useful in the measurement of blood flow and blood volume in the femoral heads. With age, physiological hemodynamic changes also increased in femoral heads. [ABSTRACT FROM AUTHOR]

We report the case of a 29-year-old Japanese man with transient osteoporosis of the left hip (TOH) following contralateral TOH, paying special attention to the initial changes on MRI. MR images showed no abnormal findings 6 weeks before the clinical manifestation, but the images just after the onset depicted a linear abnormality equivalent to a subchondral insufficiency fracture. Both radiological findings and clinical symptoms disappeared completely without any surgical intervention within 10 months. [ABSTRACT FROM AUTHOR]