Keiichiro Ueshima

Initial changes of non-traumatic osteonecrosis of femoral head in fat suppression images: bone marrow edema was not found before the appearance of band patterns

The present study examined initial changes in non-traumatic osteonecrosis of the femoral head (ONF) on T1- and T2-weighted MR images, and fat suppression images. The subjects were 57 renal transplant recipients (37 males and 20 females), whose median age at the time of transplantation was 31.5 years old (range, 10 to 58 years). Twelve patients developed band patterns (sign of established ONF) at an early postoperative period. Among them, 4 joints of 3 patients had a localized, faint signal abnormality in fat suppression images, where band pattern was confirmed later in T1- and T2-weighted images. In all the 57 patients, no bone marrow edema preceding to ONF was observed. Bone marrow edema would not be the cause of ONF in renal transplant patients. Early changes depicted in our fat suppression images would be useful information in the studies on pathogenesis of ONF.

Reliability and validity of the Japanese Orthopaedic Association hip score

BackgroundThe 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.MethodsA 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.ResultsWhen 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 was <0.70, 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.ConclusionsWe 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.

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

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.

Degree of corticosteroid treatment within the first 2 months of renal transplantation has a strong influence on the incidence of osteonecrosis of the femoral head

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.

Short-Term Results of the S-ROM-A Femoral Prosthesis: Operative Strategies for Asian Patients With Osteoarthritis

The S-ROM-A femoral prosthesis (DePuy, Warsaw, IN) is a modular cementless femoral stem system that was developed to adapt to hip joint disorders of Asian patients. Clinical results of total hip arthroplasties using the S-ROM-A femoral prosthesis were evaluated in 68 hips. The average age at the time of surgery was 57.1 years. The mean follow-up period was 27.8 months. The Harris hip score improved from 47.1 points preoperatively to 91.4 points at final follow-up. No dislocations were observed. Implant fixation was good without any evidence of osteolysis or loosening. The S-ROM-A femoral prosthesis fitted well for Asian patients who often have osteoarthritis secondary to developmental dysplasia of the hip, by providing a shorter stem and greater variety in the neck shape of the stem with a smaller diameter.

Clinical and basic research on steroid-induced osteonecrosis of the femoral head in Japan

BACKGROUND Steroid (glucocorticoid)-induced osteonecrosis of the femoral head (ONFH) in young adults has been a challenging disorder due to frequent incidence of collapse of the femoral head and resulting dysfunction of the hip joint and impairing quality of life. In Japan, the working group on ONFH in the Specific Disease Investigation Committee under auspices of the Japanese Ministry of Health, Labor and Welfare was founded in 1975, clinical and related basic research on ONFH have been continued for more than 40 years. EPIDEMIOLOGY AND CLINICAL COURSE A national epidemiologic survey in 2004 estimated that 2200 new patients per year would be diagnosed with ONFH in Japan. ONFH was associated with steroid intake (51%), heavy alcohol intake (31%), both (3%), and neither (15%). The male-to-female ratio was 5:4, and the peak decades of age at definitive diagnosis were the 40s in male patients and the 30s in females. MRI studies revealed that ONFH would have occurred in early phase after start of steroid administration and no expansion of necrotic lesion within the femoral head in spite of continued steroid use. To standardize ONFH diagnosis and treatment strategy, the Committee established validated diagnostic criteria, a radiological staging system, and type categorization. TREATMENT OPTIONS Most symptomatic patients with collapse of the femoral head require various surgical procedures. Joint preserving surgery, such as transtrochanteric rotational osteotomy and curved varus osteotomy, should be the treatment choice for young patients with healthy areas without severe collapse of the femoral head. CLINICAL AND RELATED BASIC RESEARCH Clinical and basic research has been performed to determine the pathogenesis of steroid-induced ONFH. Low hepatic CYP3A activity has been reported to significantly contribute to the risk of steroid-induced ONFH. Several gene polymorphisms related to steroid metabolism were shown to be associated with the occurrence of ONFH.

HIF-1α-induced HSP70 regulates anabolic responses in articular chondrocytes under hypoxic conditions.

We assessed whether heat shock protein 70 (HSP70) is involved in hypoxia inducible factor 1 alpha (HIF‐1α)‐dependent anabolic pathways in articular chondrocytes under hypoxic conditions. Primary rabbit chondrocytes were cultured under normoxia (20% oxygen condition) or hypoxia (1% oxygen condition). Alternatively, cells cultured under normoxia were treated with CoCl2, which induces HIF‐1α, to simulate hypoxia, or transfected with siRNAs targeting HIF‐1α (si‐HIF‐1α) and HSP70 (si‐HSP70) under hypoxia. HSP70 expression was enhanced by the increased expression of HIF‐1α under hypoxia or simulated hypoxia, but not in the presence of si‐HIF‐1α. Hypoxia‐induced overexpression of ECM genes was significantly suppressed by si‐HIF‐1α or si‐HSP70. Cell viability positively correlated with hypoxia, but transfection with si‐HIF‐1α or si‐HSP70 abrogated the chondroprotective effects of hypoxia. Although LDH release from sodium nitroprusside‐treated cells and the proportion of TUNEL positive cells were decreased under hypoxia, transfection with si‐HIF‐1α or si‐HSP70 almost completely blocked these effects. These findings indicated that HIF‐1α‐induced HSP70 overexpression increased the expression levels of ECM genes and cell viability, and protected chondrocytes from apoptosis. HIF‐1α may regulate the anabolic effects of chondrocytes under hypoxic conditions by regulating HSP70 expression.

Evaluation of the hemodynamics of the femoral head compared with the ilium, femoral neck and femoral intertrochanteric region in healthy adults : measurement with positron emission tomography (PET)

ObjectiveNon-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).MethodsThe 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 the15O-labeled carbon monoxide bolus inhalation method.ResultsBlood 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 m//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).ConclusionThe 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.

Noninvasive up-regulation of angiopoietin-2 and fibroblast growth factor-2 in bone marrow by pulsed electromagnetic field therapy

BackgroundPulsed 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.MethodsWe 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.ResultsThe 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.ConclusionThe angiogenesis-promoting function of PEMF may contribute to its mechanism to noninvasively accelerate bone fracture healing.

Blood flow and blood volume in the femoral heads of healthy adults according to age: measurement with positron emission tomography (PET).

ObjectiveTo 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).MethodsIn 16 healthy adult males (age: 20–78 years old, mean age: 42 years), blood flow was measured by means of the H215O dynamic study method, and blood volume was measured by means of the15O-labeled carbon monoxide bolus inhalations methods.ResultsBlood flow was 1.68–6.47 ml/min/100g (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).ConclusionPET 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.