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1.
Electromagn Biol Med ; 37(2): 84-94, 2018.
Article En | MEDLINE | ID: mdl-29708772

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.


Contrast Media , Electric Stimulation , Femur/blood supply , Magnetic Resonance Imaging , Osteonecrosis/physiopathology , Regional Blood Flow , Steroids/adverse effects , Animals , Disease Models, Animal , Femur/diagnostic imaging , Femur/drug effects , Femur/pathology , Male , Osteonecrosis/chemically induced , Osteonecrosis/diagnostic imaging , Rabbits , Regional Blood Flow/drug effects , Time Factors
2.
Bioelectromagnetics ; 36(5): 349-57, 2015 Jul.
Article En | MEDLINE | ID: mdl-25808585

This study was designed to evaluate femoral perfusion after pulsed electromagnetic field (PEMF) stimulation in a steroid-induced osteonecrosis rabbit model by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Steroid-induced osteonecrosis was produced by single intramuscular injection of methylprednisolone in 15 rabbits. Eight rabbits underwent PEMF stimulation (PEMF group) and seven did not (control group). DCE-MRI was performed before PEMF stimulation, immediately before steroid administration, and 1, 5, 10, and 14 days after steroid administration. Regions of interest were set in the bilateral proximal femora. Enhancement ratio (ER), initial slope (IS), and area under the curve (AUC) were analyzed. ER, IS, and AUC in the control group significantly decreased after steroid administration compared with before administration (P<0.05). In PEMF group, IS significantly decreased; however, ER and AUC showed no significant differences after steroid administration compared with before. ER and IS in PEMF group were higher than in control group until 10th day, and AUC was higher until 5th day after steroid administration (P<0.05). PEMF stimulation restrains the decrease in blood flow after steroid administration.


Electric Stimulation Therapy/methods , Femur/blood supply , Femur/physiopathology , Osteonecrosis/physiopathology , Osteonecrosis/therapy , Animals , Area Under Curve , Disease Models, Animal , Magnetic Resonance Imaging , Male , Methylprednisolone , Rabbits , Regional Blood Flow , Time Factors , Treatment Outcome
3.
J Magn Reson Imaging ; 41(4): 935-40, 2015 Apr.
Article En | MEDLINE | ID: mdl-24723501

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.


Blood Flow Velocity , Femoral Artery/physiopathology , Magnetic Resonance Angiography/methods , Methylprednisolone , Osteonecrosis/chemically induced , Osteonecrosis/physiopathology , Algorithms , Animals , Contrast Media , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Male , Osteonecrosis/pathology , Rabbits , Reproducibility of Results , Sensitivity and Specificity , Steroids
4.
Acta Orthop ; 85(3): 266-70, 2014 Jun.
Article En | MEDLINE | ID: mdl-24786907

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.


Adrenal Cortex Hormones/adverse effects , Femur Head Necrosis/diagnosis , Femur Head Necrosis/epidemiology , Kidney Transplantation , Postoperative Period , Administration, Intravenous , Administration, Oral , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adult , Aged , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Femur Head Necrosis/pathology , Humans , Incidence , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Risk Factors , Time Factors , Young Adult
5.
J Arthroplasty ; 26(7): 1088-94, 2011 Oct.
Article En | MEDLINE | ID: mdl-21676577

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.


Acetabulum/surgery , Arthroplasty, Replacement, Hip , Fluoroscopy , Hip Prosthesis , Patient Positioning , Pelvis/diagnostic imaging , Acetabulum/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Preoperative Care
6.
J Orthop Sci ; 15(5): 661-5, 2010 Sep.
Article En | MEDLINE | ID: mdl-20953928

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The angiogenesis-promoting function of PEMF may contribute to its mechanism to noninvasively accelerate bone fracture healing.


Angiopoietin-2/metabolism , Bone Marrow/metabolism , Fibroblast Growth Factor 2/metabolism , Magnetic Field Therapy , Up-Regulation , Animals , Femur , Fracture Healing , Male , Mice , Mice, Inbred ICR , Neovascularization, Physiologic , Receptor, TIE-2/metabolism , Vascular Endothelial Growth Factor A/metabolism
7.
J Orthop Sci ; 15(4): 452-8, 2010 Jul.
Article En | MEDLINE | ID: mdl-20721711

BACKGROUND: 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. METHODS: 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. RESULTS: 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 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. CONCLUSIONS: 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.


Osteoarthritis, Hip/diagnosis , Severity of Illness Index , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Female , Gait Disorders, Neurologic/diagnosis , Humans , Male , Middle Aged , Pain Measurement , Quality of Life , Range of Motion, Articular , Reproducibility of Results , Retrospective Studies , Young Adult
8.
Clin Orthop Relat Res ; 468(10): 2715-24, 2010 Oct.
Article En | MEDLINE | ID: mdl-20224959

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.


Femur Head Necrosis/epidemiology , Adult , Age Distribution , Aged , Aged, 80 and over , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Arthroplasty, Replacement, Hip/statistics & numerical data , Female , Femur Head Necrosis/diagnosis , Femur Head Necrosis/etiology , Femur Head Necrosis/surgery , Health Surveys , Humans , Japan/epidemiology , Male , Middle Aged , Risk Factors , Severity of Illness Index , Sex Distribution , Steroids/adverse effects , Surveys and Questionnaires , Time Factors , Treatment Outcome , Young Adult
9.
Acta Orthop ; 81(1): 154-60, 2010 Feb.
Article En | MEDLINE | ID: mdl-20146637

BACKGROUND AND PURPOSE: Prevention of osteonecrosis after corticosteroid administration would be important. We examined the potential of vitamin E (alpha-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 alpha-tocopherol-supplemented diet in which alpha-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 alpha-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.


Femur Head Necrosis/prevention & control , Glucocorticoids/adverse effects , Methylprednisolone/adverse effects , Osteonecrosis/prevention & control , alpha-Tocopherol/administration & dosage , Animals , Disease Models, Animal , Femur Head Necrosis/chemically induced , Glucocorticoids/administration & dosage , Male , Methylprednisolone/administration & dosage , Osteonecrosis/chemically induced , Osteonecrosis/pathology , Rabbits , Vitamins/administration & dosage
10.
J Arthroplasty ; 25(3): 369-74, 2010 Apr.
Article En | MEDLINE | ID: mdl-19195834

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.


Arthritis, Rheumatoid/surgery , Arthroplasty, Replacement, Hip/instrumentation , Femur Head Necrosis/surgery , Hip Joint/diagnostic imaging , Hip Prosthesis , Osteoarthritis, Hip/surgery , Adult , Aged , Aged, 80 and over , Arthritis, Rheumatoid/diagnostic imaging , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Female , Femur Head Necrosis/diagnostic imaging , Follow-Up Studies , Hip Joint/surgery , Hip Prosthesis/adverse effects , Humans , Incidence , Kaplan-Meier Estimate , Male , Middle Aged , Osteoarthritis, Hip/diagnostic imaging , Osteolysis/epidemiology , Prosthesis Failure , Radiography , Retrospective Studies , Treatment Outcome
11.
J Arthroplasty ; 24(8): 1193-9, 2009 Dec.
Article En | MEDLINE | ID: mdl-19369026

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.


Arthroplasty, Replacement, Hip/methods , Hip Dislocation, Congenital/surgery , Hip Prosthesis , Osteoarthritis, Hip/surgery , Adult , Aged , Aged, 80 and over , Asian People , Female , Humans , Male , Middle Aged , Treatment Outcome
12.
Geriatr Gerontol Int ; 9(1): 69-74, 2009 Mar.
Article En | MEDLINE | ID: mdl-19260982

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.


Bone and Bones/metabolism , Hip Fractures/epidemiology , Hip Fractures/etiology , Osteoporosis/complications , Osteoporosis/metabolism , Aged , Aged, 80 and over , Alkaline Phosphatase/blood , Amino Acids/urine , Female , Humans , Japan/epidemiology , Middle Aged , Risk Factors
13.
Acta Orthop ; 79(5): 631-6, 2008 Oct.
Article En | MEDLINE | ID: mdl-18839369

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.


Femur Head Necrosis/etiology , Glucocorticoids/administration & dosage , Kidney Transplantation/adverse effects , Postoperative Complications/etiology , Adolescent , Adult , Cyclosporine/administration & dosage , Cyclosporine/adverse effects , Dose-Response Relationship, Drug , Female , Femur Head Necrosis/chemically induced , Glucocorticoids/adverse effects , Graft Rejection , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Male , Methylprednisolone/administration & dosage , Methylprednisolone/adverse effects , Postoperative Complications/chemically induced , Prednisolone/administration & dosage , Prednisolone/adverse effects , Risk Factors , Tacrolimus/administration & dosage , Tacrolimus/adverse effects , Time Factors
14.
J Orthop Sci ; 13(4): 297-303, 2008 Jul.
Article En | MEDLINE | ID: mdl-18696186

BACKGROUND: 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. METHODS: 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. RESULTS: The synergistic index between the ABCB1 and CBP genes was >1.00 (1.99), revealing the presence of an interaction. CONCLUSIONS: 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.


ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , CREB-Binding Protein/genetics , Femur Head Necrosis/chemically induced , Femur Head Necrosis/genetics , Polymorphism, Single Nucleotide/genetics , Steroids/adverse effects , ATP Binding Cassette Transporter, Subfamily B , Adult , Apolipoproteins B/genetics , Biomarkers , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Odds Ratio , Young Adult
15.
J Orthop Sci ; 13(3): 202-10, 2008 May.
Article En | MEDLINE | ID: mdl-18528653

BACKGROUND: The aim of this study was to clarify the significance of subchondral bone in the pathology of osteoarthritis (OA) by investigating the expression of inflammatory cytokines, proteases, and receptor activator of NF-kappaB ligand (RANKL)/receptor activator of NF-kappaB (RANK)/osteoprotegerin (OPG) involved in cartilage degeneration. METHODS: Subchondral bone was obtained from 19 patients diagnosed with knee OA and 4 patients diagnosed with femoral neck fracture. Subchondral bone osteoblasts (SBOs) were isolated, and total RNA was extracted. Messenger RNA expression of inflammatory cytokines, proteases, and RANKL/RANK/OPG were analyzed using a real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Real-time RT-PCR showed that mRNA expressions of interleukin-6 (IL-6), matrix metalloproteinase-13 (MMP-13), and RANKL were significantly enhanced in OA SBOs compared to SBOs without OA. The expressions of these genes was greater in patients with severe cartilage damage than in those with mild cartilage damage. A high correlation between mRNA expression of IL-6 and that of MMP-13 was found in OA SBOs. CONCLUSION: The increases in IL-6, MMP-13, and RANKL expression in OA SBOs suggest that in subchondral bone OA progression involves abnormal osseous tissue remodeling, which induces mechanical property changes. Cartilage degeneration in OA may also be due, at least in part, to IL-6 and MMP-13 produced by SBOs. Comprehensive research on these pathological features may lead to the development of more effective therapies for OA by administration of molecules that affect bone remodeling and metabolism.


Interleukin-6/metabolism , Matrix Metalloproteinase 13/metabolism , Osteoarthritis, Knee/metabolism , Osteoblasts/metabolism , RANK Ligand/metabolism , Aged , Aged, 80 and over , Bone Remodeling/physiology , Case-Control Studies , Cells, Cultured , Female , Femur Head/metabolism , Gene Expression Profiling , Humans , Interleukin-6/genetics , Male , Matrix Metalloproteinase 13/genetics , Middle Aged , RANK Ligand/genetics , RNA, Messenger/metabolism
16.
Clin Orthop Relat Res ; 466(5): 1068-73, 2008 May.
Article En | MEDLINE | ID: mdl-18350347

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.


Electric Stimulation Therapy/methods , Electromagnetic Fields , Femur Head Necrosis/prevention & control , Femur/radiation effects , Adipocytes/radiation effects , Animals , Bone Marrow Cells/radiation effects , Cell Size , Disease Models, Animal , Electric Stimulation Therapy/instrumentation , Equipment Design , Femur/pathology , Femur Head Necrosis/chemically induced , Femur Head Necrosis/pathology , Male , Methylprednisolone , Rabbits , Time Factors
17.
J Bone Miner Metab ; 25(5): 320-5, 2007.
Article En | MEDLINE | ID: mdl-17704997

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.


CREB-Binding Protein/genetics , Kidney Transplantation/methods , Osteonecrosis/genetics , Polymorphism, Single Nucleotide , Steroids/adverse effects , Adolescent , Adult , Chi-Square Distribution , Child , Female , Gene Frequency , Genotype , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Male , Middle Aged , Nuclear Receptor Coactivator 2/genetics , Odds Ratio , Osteonecrosis/chemically induced , Steroids/therapeutic use
18.
Clin Calcium ; 17(6): 856-62, 2007 Jun.
Article Ja | MEDLINE | ID: mdl-17548924

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.


Femur Head Necrosis/chemically induced , Glucocorticoids/adverse effects , Adult , Aged , Female , Femur Head/diagnostic imaging , Femur Head/pathology , Femur Head Necrosis/classification , Femur Head Necrosis/diagnosis , Femur Head Necrosis/physiopathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Radiography , Radionuclide Imaging
19.
Clin Calcium ; 17(6): 894-900, 2007 Jun.
Article Ja | MEDLINE | ID: mdl-17548929

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.


Femur Head Necrosis/chemically induced , Femur Head Necrosis/genetics , Glucocorticoids/adverse effects , Polymorphism, Genetic , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Apolipoproteins B/genetics , Cyclic AMP Response Element-Binding Protein/genetics , Cytochrome P-450 Enzyme System/genetics , Femur Head Necrosis/prevention & control , Gene Frequency , Humans
20.
J Orthop Sci ; 12(3): 199-206, 2007 May.
Article En | MEDLINE | ID: mdl-17530370

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


Apolipoproteins B/genetics , DNA/genetics , Femur Head Necrosis/genetics , Glucocorticoids/adverse effects , Kidney Transplantation , Polymorphism, Restriction Fragment Length , Prednisolone/adverse effects , Administration, Oral , Adolescent , Adult , Apolipoprotein A-I/blood , Apolipoprotein A-I/genetics , Apolipoproteins B/blood , Biomarkers/blood , Child , Female , Femur Head Necrosis/blood , Femur Head Necrosis/chemically induced , Follow-Up Studies , Gene Frequency , Glucocorticoids/administration & dosage , Graft Rejection/prevention & control , Humans , Injections, Intravenous , Male , Middle Aged , Polymerase Chain Reaction , Postoperative Complications , Prednisolone/administration & dosage , Prognosis , Retrospective Studies , Risk Factors
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