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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.

To identify whether differences exist in the outcomes between patients undergoing hemodialysis and elderly nonhemodialysis patients with a femoral neck fracture.

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.

Conventional methods of quantitative Na18F positron emission tomography require multiple arterial blood sampling in order to obtain the input function, and the procedures are invasive and complicated. This study aims to establish a simplified and reliable technique for obtaining the input function.

To investigate the usefulness of epiphyseal quotient (EQ) measurement for outcome prediction in patients with Legg–Calvé–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.

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.

We investigated risk factors for osteonecrosis of the femoral head (ONF) in renal transplant recipients, who are susceptible to the disease. Among 287 renal transplant recipients, 18 ONF patients with enough data were included, and 18 age- and sex-matched recipients without ONF were nominated as reference cases. Risk factors were analyzed using a conditional logistic regression method. There were no differences between the ONF patients and the reference cases regarding the types of immunosuppressant or the donor (living or cadaveric, father or mother, matching blood type and human leukocyte antigens). The daily oral steroid dosage (prednisolone 25.0 mg/day or more) and blood urea nitrogen level 2 months after transplantation were the only factors with relevance to the occurrence of ONF. We propose that oral steroid dosages should be low or reduced after renal transplantation, and acute rejection should be controlled with pulsed therapy.

We investigated risk factors for osteonecrosis of the femoral head (ONF) in renal transplant recipients, who are susceptible to the disease. Among 287 renal transplant recipients, 18 ONF patients with enough data were included, and 18 age- and sex-matched recipients without ONF were nominated as reference cases. Risk factors were analyzed using a conditional logistic regression method. There were no differences between the ONF patients and the reference cases regarding the types of immunosuppressant or the donor (living or cadaveric, father or mother, matching blood type and human leukocyte antigens). The daily oral steroid dosage (prednisolone 25.0?mg/day or more) and blood urea nitrogen level 2 months after transplantation were the only factors with relevance to the occurrence of ONF. We propose that oral steroid dosages should be low or reduced after renal transplantation, and acute rejection should be controlled with pulsed therapy.

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 ABCB1C3435T (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 ABCB1genotypes 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 ABCB1C3435T (CC, CT, TT), and in those who did and did not develop ONF. The ABCB13435TT 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 ABCB12677 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.

We radiographically investigated 36 hips in 34 patients with osteoarthritis of the hip who had undergone total hip arthroplasty. Their mean age was 59.2 years (range 36–79 years), and the mean follow-up period was 11.2 years (range 10–14 years). The long-term outcome and the chronological changes in the bulk autograft were examined. The acetabular component of the prosthesis was a Lord-type threaded cup with a smooth surface. At follow-up, bone absorption was minor in 17 joints, moderate in 11, and major in 8. The hips with graft coverage of ≥20% (group A) had a significantly higher loosening rate than hips with coverage of <20% (group B) (P< 0.05). The cup position changed markedly in group A. Our findings indicate that graft coverage should be less than 20% when a bulk graft is used together with a smooth-surfaced cementless cup.

We radiographically investigated 36 hips in 34 patients with osteoarthritis of the hip who had undergone total hip arthroplasty. Their mean age was 59.2 years (range 36–79 years), and the mean follow-up period was 11.2 years (range 10–14 years). The long-term outcome and the chronological changes in the bulk autograft were examined. The acetabular component of the prosthesis was a Lord-type threaded cup with a smooth surface. At follow-up, bone absorption was minor in 17 joints, moderate in 11, and major in 8. The hips with graft coverage of ?20% (group A) had a significantly higher loosening rate than hips with coverage of «20% (group B) ( P « 0.05). The cup position changed markedly in group A. Our findings indicate that graft coverage should be less than 20% when a bulk graft is used together with a smooth-surfaced cementless cup.

With advanced organ transplantation technology, steroid-induced osteonecrosis of the femoral head (ONF) is one of the most troublesome complications. Steroid sensitivity varies among individuals, and the involvement of polymorphism of various genes relating to steroid metabolism is suggested. The present study investigated the relation between single nucleotide polymorphism (SNP) on the DNA sequence of cytochrome P450and ONF development. The subjects were 80 renal transplant patients. Genome DNA was obtained from the peripheral blood, and SNP analyses for CYP3A4, CYP2D6, and CYP2C19 were conducted using various methods: direct sequencing, polymerase chain reaction restriction fragment length polymorphism, and DNA Chip. The relation between ONF development and SNP was statistically analyzed. It is useful if the generating risk judged according to SNPs to prevention of steroid-induced ONF is possible. This time, SNPs, which are clearly related to ONF, were not accepted, although the possibility that SNP related to steroid metabolism is involved in ONF development is important. We think that it is necessary to examine this area more closely.

Thermotherapy has been applied to various joint diseases and injuries, but its direct effects on articular cartilage have remained unclear. The present study examined the effects on cell viability and metabolism by using the chondrocyte-like cell line HCS-2/8. The temperatures and durations of heat stimulation were 39°, 41°, 43°, and 45°C for 15 or 30min. After heat stimulation of 41°C or lower for 15 or 30 min, cell viability increased and proteoglycan metabolism was accelerated, whereas after stimulation at 43°C or higher for 30min the viability and metabolism decreased. These results indicate that appropriate heat stimulation positively affects cell viability and the proteoglycan metabolism of articular cartilage, whereas too much heat stimulation produces negative effects. Clinical efficacy is therefore determined by the overall thermal dose. When the appropriate combination of temperature and duration is found, thermotherapy for diseases and injury of articular cartilage can be highly useful in clinical practice.

Abstract:  Thermotherapy has been applied to various joint diseases and injuries, but its direct effects on articular cartilage have remained unclear. The present study examined the effects on cell viability and metabolism by using the chondrocyte-like cell line HCS-2/8. The temperatures and durations of heat stimulation were 39°, 41°, 43°, and 45°C for 15 or 30 min. After heat stimulation of 41°C or lower for 15 or 30 min, cell viability increased and proteoglycan metabolism was accelerated, whereas after stimulation at 43°C or higher for 30 min the viability and metabolism decreased. These results indicate that appropriate heat stimulation positively affects cell viability and the proteoglycan metabolism of articular cartilage, whereas too much heat stimulation produces negative effects. Clinical efficacy is therefore determined by the overall thermal dose. When the appropriate combination of temperature and duration is found, thermotherapy for diseases and injury of articular cartilage can be highly useful in clinical practice.

Abstract:  With advanced organ transplantation technology, steroid-induced osteonecrosis of the femoral head (ONF) is one of the most troublesome complications. Steroid sensitivity varies among individuals, and the involvement of polymorphism of various genes relating to steroid metabolism is suggested. The present study investigated the relation between single nucleotide polymorphism (SNP) on the DNA sequence of cytochrome P450 and ONF development. The subjects were 80 renal transplant patients. Genome DNA was obtained from the peripheral blood, and SNP analyses for CYP3A4, CYP2D6, and CYP2C19 were conducted using various methods: direct sequencing, polymerase chain reaction restriction fragment length polymorphism, and DNA Chip. The relation between ONF development and SNP was statistically analyzed. It is useful if the generating risk judged according to SNPs to prevention of steroid-induced ONF is possible. This time, SNPs, which are clearly related to ONF, were not accepted, although the possibility that SNP related to steroid metabolism is involved in ONF development is important. We think that it is necessary to examine this area more closely.

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.

Abstract: A 49-year-old Japanese man who had non-traumatic osteonecrosis of the femoral head with a wide necrotic lesion received transtrochanteric anterior rotational osteotomy combined with vascularized iliac bone grafting. After the bone graft (6 × 1.5 cm) was collected, the femoral head was anteriorly rotated by 90°. A bone tunnel of 1.2 cm in diameter was prepared on the necrotic lesion adjacent to the intact area from the anterior part of the femoral neck to inside the femoral head. The bone graft was trimmed to the size of this bone tunnel, and inserted up to immediately below the articular surface. In the monitoring using T1-weighted magnetic resonance imaging (MRI), the low signal-intensity area between the bone graft and intact area had disappeared, and a high signal-intensity area on the weight-bearing portion of the femoral head had extended. With modifications on the insertion point of the bone graft, transtrochanteric anterior rotational osteotomy combined with vascularized iliac bone graft would be a useful means to preserve the femoral head in large non-traumatic osteonecrosis of the femoral head.

A 49-year-old Japanese man who had non-traumatic osteonecrosis of the femoral head with a wide necrotic lesion received transtrochanteric anterior rotational osteotomy combined with vascularized iliac bone grafting. After the bone graft (6 × 1.5cm) was collected, the femoral head was anteriorly rotated by 90°. A bone tunnel of 1.2cm in diameter was prepared on the necrotic lesion adjacent to the intact area from the anterior part of the femoral neck to inside the femoral head. The bone graft was trimmed to the size of this bone tunnel, and inserted up to immediately below the articular surface. In the monitoring using T1-weighted magnetic resonance imaging (MRI), the low signal-intensity area between the bone graft and intact area had disappeared, and a high signal-intensity area on the weight-bearing portion of the femoral head had extended. With modifications on the insertion point of the bone graft, transtrochanteric anterior rotational osteotomy combined with vascularized iliac bone graft would be a useful means to preserve the femoral head in large non-traumatic osteonecrosis of the femoral head.

Abstract: Severe osteoarthritis due to acetabular dysplasia (n = 17) was treated with valgus-extension osteotomy, and the patients' clinical outcomes 10–14 years after operation were evaluated according to clinical factors (Japanese Orthopaedic Association hip score; JOA score) and by roentgenography. The mean JOA score 10 years or later had improved by 22 points compared with the preoperative score. On roentgenography, joints which had preoperative roof osteophyte had better postoperative formation of roof osteophyte. The JOA score was higher in the 12 joints which had osteophyte 5 mm or longer than in those joints with osteophyte that was 5 mm or shorter. Postoperative joint space widening occurred in 15 joints (88.2%) 3–6 months postoperatively, and it reached the maximum at 3–5 years. In patients who had a large bone cyst in the femoral head preoperatively, the cyst collapsed, and deformation of femoral head occurred after operation, but remodeling of the joint surface occurred naturally and the congruity improved. In the 6 joints in which the preoperative acetabular head index was less than 60% and the acetabular angle was larger than 30°, the JOA score at 10 years or later was lower than that of the other joints. Based on these findings, valgus-extension osteotomy was evaluated as a useful surgical method for advanced or terminal osteoarthritis in young or middle-aged patients. Predictive factors for long-term prognosis would be the preoperative length of roof osteophyte, joint space widening, and the degree of femoral head covering.

Severe osteoarthritis due to acetabular dysplasia (n= 17) was treated with valgus-extension osteotomy, and the patients’ clinical outcomes 10–14 years after operation were evaluated according to clinical factors (Japanese Orthopaedic Association hip score; JOA score) and by roentgenography. The mean JOA score 10 years or later had improved by 22 points compared with the preoperative score. On roentgenography, joints which had preoperative roof osteophyte had better postoperative formation of roof osteophyte. The JOA score was higher in the 12 joints which had osteophyte 5mm or longer than in those joints with osteophyte that was 5mm or shorter. Postoperative joint space widening occurred in 15 joints (88.2%) 3–6 months postoperatively, and it reached the maximum at 3–5 years. In patients who had a large bone cyst in the femoral head preoperatively, the cyst collapsed, and deformation of femoral head occurred after operation, but remodeling of the joint surface occurred naturally and the congruity improved. In the 6 joints in which the preoperative acetabular head index was less than 60% and the acetabular angle was larger than 30°, the JOA score at 10 years or later was lower than that of the other joints. Based on these findings, valgus-extension osteotomy was evaluated as a useful surgical method for advanced or terminal osteoarthritis in young or middle-aged patients. Predictive factors for longterm prognosis would be the preoperative length of roof osteophyte, joint space widening, and the degree of femoral head covering.

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.