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ABSTRACT: Diagnosis of sarcopenia is based on the combination of physical-performance assessment and muscle-mass measurement. Physical performance was estimated by gait speed and grip strength. Common measuring procedures for skeletal muscle mass were dual energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA) . Skeletal muscle mass index (SMI) was calculated from following formula ; [SMI (kg/m(2)) = (arm lean mass + leg lean mass) /height(2)] . Sarcopenia and sarcopenic leg are associated with poor body balance, falls, and subsequent fracture. Treatment of sarcopenia may result in successful prevention of fall and fracture for frail elderly.
Clinical calcium 05/2013; 23(5):707-12.
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ABSTRACT: Joint disease is one of the most frequent causes of reaching a state requiring care by others. Thus, it is very important to cope with osteoarthritis (OA) in order to maintain the physical independence of elderly people. Xp findings of OA in the knee, which is the most commonly affected joint, do not correlate well with pain ; hence, on the diagnosis, MRI is useful to know the pathology of subchondral bone, cartilage or meniscus. In OA cartilage, increased degradation and decreased production of major matrix components, like type II collagen and aggrecan occur, as well as chondrocyte hypertrophy or apoptosis. In the meantime, general changes in the aging process, such as the changes of autophagy or energy metabolism, have also recently been reported. Since OA treatments at present are just against symptoms, like by NSAIDS or arthroplasty, the development of new treatment methods is expected, based on the clarification of the pathology, including consideration of the relations with aging of bone and muscles, or with metabolic syndrome.
Clinical calcium 01/2013; 23(1):15-22.
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Keizo Sakamoto,
Naoto Endo, Atsushi Harada,
Takenori Sakada,
Kazuyo Tsushita,
Kiyoshi Kita,
Hiroshi Hagino,
Akinori Sakai,
Noriaki Yamamoto,
Tetsunori Okamoto,
Meigen Liu,
Akatsuki Kokaze,
Hiromichi Suzuki
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ABSTRACT: BACKGROUND: Maintaining or improving motor (balance) ability is essential to extending the healthy lifespan of elderly people, and developing effective and efficient strategies to prevent falls of elderly people is an urgent. The purpose of this study was to determine the effects of balance exercise on fall and fracture prevention for elderly people with poor balance. METHODS: A 6-month, randomized controlled trial was conducted to verify whether one-leg standing with eyes open for a total of 1 min, three times a day (dynamic flamingo exercise) prevents falls and fractures. Setting and participants were elderly people ≥75 years of age and one-leg standing time ≤15.0 s living in their own home. They were visiting orthopaedic clinics for orthopaedic handicaps. Subjects with poor balance were allowed to hold on to something. If a subject's lifted leg touched the ground during the exercise, they were allowed to lift it again and continue so that they stood on one leg for a total of 60 s. RESULTS: The dynamic flamingo exercise group (410 people; 86 men, 324 women) and the no exercise group (455 people; 78 men, 377 women) were compared. After dynamic flamingo exercise for 6 months, significant differences were seen in the increase in one-leg standing time with eyes open (men right/left, women right/left), in the improvement in independence in daily living (women), number of people who fell during the 6 months (women), and adverse events (women). The number of fractures was not significantly different for men or women. CONCLUSIONS: Dynamic flamingo exercise prevents falls but no significant difference was demonstrated in fracture prevention in elderly women with poor balance.
Journal of Orthopaedic Science 11/2012; · 0.84 Impact Factor
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ABSTRACT: Aim: Sarcopenia-related falls and fractures are becoming an emerging problem as a result of rapid aging worldwide. We aimed to investigate the prevalence of sarcopenia by estimating the muscle mass of the arms and legs of patients with and without hip fracture. Methods: This cross-sectional study examined 357 patients immediately after a hip fracture (the HF group) and in 2511 patients from an outpatient clinic who did not have a hip fracture (the NF group) at single institution in Japan. We carried out whole-body dual energy X-ray absorptiometry to analyze body composition with skeletal muscle mass index (SMI; lean mass / height(2) ) and bone mineral density (BMD). We carried out stepwise logistic regression analysis to determine the factors associated with a hip fracture. Results: Lower appendicular SMI (P < 0.001), leg SMI (P < 0.001), and higher prevalence of sarcopenia (P < 0.001) were observed in the HF group after controlling for age and sex. The arm SMI was similar in both groups (P > 0.95). In multivariate analysis, the presence of sarcopenia, older age and lower BMD were associated with the occurrence of a hip fracture (OR 1.476, P = 0.002; OR 1.103, P < 0.001; OR 0.082, P < 0.001; respectively). Conclusion: This study showed a higher prevalence of sarcopenia and more reduced leg muscle mass in patients after a hip fracture than in the outclinic patients who did not have hip fractures. The results imply sarcopenia can be a risk factor for a hip fracture. Geriatr Gerontol Int 2012; ••: ••-••.
Geriatrics & Gerontology International 07/2012;
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ABSTRACT: Aim: Near-infrared spectroscopy (NIRS) allows estimation of the percentage of body fat (%BF) regardless of the patient's posture; thus, it is useful for assessment of elderly patients with severe decline of basic activity who cannot hold a standing position. However, the accuracy by which the near-infrared light emitted from NIRS reflects subcutaneous tissue is unknown. The aim of this study was to assess how correctly NIRS reflects the subcutaneous fat and muscle thickness derived from ultrasonography in community-dwelling elderly. Methods: A total of 93 community-dwelling older adults aged 65 years and older were enrolled in this study (mean 75.8 years, 6.7 SD). Participants were assessed according to optical density (OD) measurements by NIRS, subcutaneous fat and muscle thickness by ultrasonography, and muscle strength. Pearson's correlation coefficients were calculated for each sex. Stepwise multiple regression analysis was used to identify factors that contributed to OD for each sex. Results: OD measured at the forearm and thigh were significantly correlated with subcutaneous fat thickness. In stepwise multiple regression analyses, subcutaneous fat thickness was found to be a significant determinant of OD in men (forearm β = -0.37, P = 0.01; thigh β = -0.63, P < 0.001) and women (forearm β = -0.50, P < 0.001; thigh: β = -0.52, P < 0.001). Conclusions: These results suggest that NIRS can appropriately estimate fat-free mass. By adding other variables to OD as the predictive variable, skeletal muscle mass might be estimated in the elderly population. Geriatr Gerontol Int 2012; ••: ••-••.
Geriatrics & Gerontology International 07/2012;
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Keizo Sakamoto,
Toshitaka Nakamura,
Hiroshi Hagino,
Naoto Endo,
Satoshi Mori,
Yoshiteru Muto, Atsushi Harada,
Tetsuo Nakano,
Seizo Yamamoto,
Kazuhiro Kushida,
Katsuro Tomita,
Mitsuo Yoshimura,
Hiroshi Yamamoto
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ABSTRACT: BackgroundThe aim of this study was to assess the disability and mortality of hip fractures 1 year after initial visit (postoperatively)
at fixed-point hospitals selected by the Japanese Orthopaedic Association Committee on Osteoporosis.
MethodA total of 158 core orthopedic hospitals were selected for participation in this research. Subjects were all aged 65 years
and older with hip fractures at the selected hospitals between January 1, 1999 and December 31, 2001. A prognostic survey
of activities of daily living (ADL), assessed by the long-term care insurance criteria established by the Ministry of Health,
Labour, and Welfare of Japan was performed 1 year after the initial visit.
ResultsA total of 1992 hip fractures in patients aged 65 to 111 years were treated over the 3 years from 1999 to 2001. Among the
1992 patients, 4537 had femoral neck fractures and 6217 had trochanteric fractures. Surgical treatment was chosen for 85.6%
of the femoral neck fractures and 88.2% of the trochanteric fractures. The mean duration from fracture to admission was 3.1
days, and the mean duration from admission to surgery was 11.2 days. The mean duration from surgery to discharge over the
3-year period was 49.8 days. Before hip fracture, the ratio of patients with J1 (“able to go out freely utilizing public transportation”
or J2 (“able to visit immediate neighbors independently” on the long-term care insurance criteria was 50.9%. At 1 year after
the initial visit, that result represented a decrease of 24.1 percentage points before hip fracture. A total of 70 patients
died before undergoing surgery. In the present study, the 1-year mortality rate for the entire patient population over the
3-year period was 10.1%.
ConclusionsHip fracture patients show a decrease in the ADL score 1 year after the initial visit. Compared to other countries, the duration
of hospitalization is longer in Japan, but the mortality rate is lower.
Journal of Orthopaedic Science 04/2012; 11(2):127-134. · 0.84 Impact Factor
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ABSTRACT: Aim: Near infrared spectroscopy has been reported to have a high reliability and accuracy in assessing the percentage of body fat. However, whether muscle mass can be accurately estimated using this method has not been established. This study examined whether a near infrared spectroscopy method could estimate appendicular muscle mass and fat mass, with dual-energy X-ray absorptiometry as the standard method for comparison. Methods: A total of 20 orthopedic inpatients (mean age 73.2 ± 6.8 years) were recruited for this study. Their body composition was assessed using near infrared spectroscopy and dual-energy X-ray absorptiometry. Appendicular muscle mass and fat mass were estimated from height, weight and optical densities. Results: The optical densities for the upper arm (biceps, triceps) and forearm (flexor carpi radialis) were significantly correlated with appendicular muscle mass (r = 0.534 to 0.623) or fat mass (r = -0.483 to -0.827). Estimated appendicular muscle mass and fat mass explained 89% and 80% of the variance in the dual-energy X-ray absorptiometry-derived muscle mass and fat mass estimates using height, weight and optical density values of the proximal flexor carpi radialis. Conclusions: Near infrared spectroscopy is a useful method to assess not only fat mass, but also muscle mass in older adults. Geriatr Gerontol Int 2012; ••: ••-••.
Geriatrics & Gerontology International 02/2012; 12(4):652-8.
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ABSTRACT: To determine the approximate percentage of women in nursing homes who have vitamin D deficiency and to investigate whether, in assessing vitamin D status in elderly women, there are problems with measuring only 25 hydroxy-vitamin D(3) (25(OH)D(3) ) and whether decreased vitamin D activation as a result of poor renal function needs to be considered.
Cross-sectional study.
Forty-eight nursing homes in Japan.
Four hundred three women with a mean age of 86.5 living in nursing homes who had participated in a clinical trial for hip protectors and were not bedridden.
At the start of the trial, in addition to general biochemical data, 25(OH)D(3) , 1,25-dihydroxy-vitamin D(3) (1,25(OH)(2) D(3) ), intact parathyroid hormone (intact PTH), calcium (Ca), phosphorus (P), bone alkaline phosphate (BAP), cross-linked N-telopeptide of type I collagen (NTx), and osteocalcin were measured in participants' blood, and statistical analysis was performed.
25(OH)D(3) , which is thought to reflect vitamin D status in the body, was surveyed and found to have a mean value of 16.7 ng/mL. 25(OH)D(3) was less than 16 ng/mL in 49.1% of all participants. Creatinine clearance (CCr) was less than 30 mL/min in 20.1% of participants. Participants with serum 25(OH)D(3) less than 16 ng/mL and CCr less than 30 mL/min had significantly higher levels of intact PTH and serum NTx. Participants with a CCr less than 30 mL/min had significantly lower levels of 1,25(OH)(2) D(3) .
Frail elderly adults living in nursing homes with poor renal function had lower 1,25(OH)(2) D(3) and higher intact PTH levels and were thus thought to have poorer vitamin D activating capacity. Supplementation with cholecalciferol may be insufficient in people who have poor renal function.
Journal of the American Geriatrics Society 02/2012; 60(2):251-5. · 3.74 Impact Factor
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ABSTRACT: Bone mineral density (aBMD) is equivalent to bone mineral content (BMC) divided by area. We rechecked the significance of aBMD changes in aging by examining BMC and area separately. Subjects were 1167 community-dwelling Japanese men and women, aged 40-79 years. ABMDs of femoral neck and lumbar spine were assessed by DXA twice, at 6-year intervals. The change rates of BMC and area, as well as aBMD, were calculated and described separately by the age stratum and by sex. In the femoral neck region, aBMDs were significantly decreased in all age strata by an increase in area as well as BMC loss in the same pattern in both sexes. In the lumbar spine region, aBMDs decreased until the age of 60 in women, caused by the significant BMC decrease accompanying the small area change. Very differently in men, aBMDs increased after their 50s due to BMC increase, accompanied by an area increase. Separate analyses of BMC and area change revealed that the significance of aBMD changes in aging was very divergent among sites and between sexes. This may explain in part the dissociation of aBMD change and bone strength, suggesting that we should be more cautious when interpreting the meaning of aBMD change.
Journal of osteoporosis. 01/2012; 2012:642486.
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ABSTRACT: Serum 25-hydroxyvitamin D (25(OH)D) is used as an index that reflects the level of vitamin D. We have previously reported, on the basis of a study in Sado in Niigata, that patients with hip fracture have lower serum 25(OH)D levels than non-hip-fracture cases. In this study, the serum 25(OH)D status in hip-fracture cases was examined in four regions in Japan. Although most hip-fracture patients have experienced past spine-compression fractures, the relationship of these fractures and 25(OH)D is unknown. Therefore, we also examined the 25(OH)D level in spine-compression fracture patients in the same locations and time periods.
The levels of 25(OH)D, intact parathyroid hormone (intact PTH), undercarboxylated osteocalcin (ucOC), urine N-terminal crosslinking telopeptide of type I collagen (NTX), and bone mineral density were examined in patients with hip and spine fracture due to osteoporosis in several regions in Japan.
There were no significant differences in age, BMI, serum 25(OH)D, serum intact PTH, and serum ucOC among the regions. Levels of serum 25(OH)D were low in patients with hip fracture and spine fracture. The average serum 25(OH)D level was significantly lower in hip-fracture patients than in spine-fracture patients (16.3 vs. 18.1 ng/mL, P < 0.05). High serum ucOC was found in 37% of hip-fracture patients and 44% of spine-fracture patients.
Both hip and spine-fracture patients have vitamin D insufficiency, with similar results found in elderly patients in four areas of Japan. The severity of this condition tends to be more serious in hip-fracture patients than in spine-fracture patients.
Journal of Orthopaedic Science 05/2011; 16(4):418-23. · 0.84 Impact Factor
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Shiro Imagama,
Yukihiro Matsuyama,
Yoshihito Sakai,
Zenya Ito,
Norimitsu Wakao,
Masao Deguchi,
Yudo Hachiya,
Yoshimitsu Osawa,
Hisatake Yoshihara,
Mitsuhiro Kamiya, [......],
Yuji Matsubara,
Manabu Goto,
Koji Sato,
Shigehiko Ito,
Koji Maruyama,
Makoto Yanase,
Yoshihiro Ishida,
Naoto Kuno,
Takao Hasegawa,
Naoki Ishiguro
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ABSTRACT: Prospective, multicenter study.
To conduct peripheral arterial disease (PAD) screening on intermittent claudication (IC) in patients with lumbar spinal canal stenosis (LSCS) to examine the relationships among combined LSCS and PAD, symptoms, and physical findings.
IC occurs due to two underlying diseases, LSCS and PAD, and has an increasing prevalence with the aging of society. Reliable diagnosis of PAD is critical for appropriate conservative management of IC patients with LSCS in an Orthopedic Surgery Outpatient Department (OSOPD).
PAD tests were prospectively conducted in 201 patients with IC and LSCS who initially visited an OSOPD at a hospital affiliated with the Nogoya Spine Group. Occurrence of PAD as a complication was assessed using ankle brachial pressure index (ABI) and toe brachial pressure index (TBI) tests. PAD was diagnosed in patients with ABI ≤ 0.9 or TBI ≤ 0.6, and the relationship of the occurrence of PAD with symptoms and physical findings such as abnormal arterial pulses was investigated.
Combined LSCS and PAD was found in 52 patients (26%), with 45 cases (22%) diagnosed on the basis of TBI test in patients with a normal ABI. Of the patients with PAD, many suffered from risk factors for PAD, with a significantly higher frequency of PAD in patients with hyperlipidemia (P < 0.05). PAD also occurred significantly more frequently in patients with abnormal pulses in the popliteal (P < 0.05), posterior tibial (P < 0.0001), and dorsal pedis (P < 0.0001) arteries; however, the sensitivity of these tests for PAD diagnosis was relatively low, at 34%, 60% and 68%, respectively.
The results of the prospective study define the rate of occurrence of combined LSCS and PAD using ABI and TBI tests for the first time, and the findings suggest that screening for PAD should be conducted in LSCS patients. ABI and TBI tests are necessary for PAD screening in outpatients, whereas observation of the arterial pulse in the lower extremities is necessary but not sufficient for PAD diagnosis.
Spine 01/2011; 36(15):1204-10. · 2.08 Impact Factor
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Hiroshi Hagino,
Keizo Sakamoto, Atsushi Harada,
Toshitaka Nakamura,
Yoshiteru Mutoh,
Satoshi Mori,
Naoto Endo,
Tetsuo Nakano,
Eiji Itoi,
Kiyoshi Kita,
Noriaki Yamamoto,
Kiyoshi Aoyagi,
Kaoru Yamazaki
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ABSTRACT: To elucidate the characteristics of hip fractures and the current status of their treatment in Japan, the Japanese Orthopaedic Association (JOA) conducted a nationwide hip fracture survey from 1998 to the present. The aim of the current report was to present the changes in patient distribution by age and fracture type, cause of fracture, treatment selection, and duration of hospitalization for a study period of one decade.
A tally of all hip fractures that occurred in patients between 2001 and 2008 was conducted in JOA-authorized hospitals and in Japanese Clinical Orthopaedic Association (JCOA) hospitals. Registration forms were sent to these hospitals each year, and registration was performed based on their hospital records.
The mean response rate was 51.8%, and the total number of patients aged ≥35 with new hip fractures between 2001 and 2008 was 402 760. A drastic increase in the number of patients, especially those aged ≥90 was observed over the course of the decade. More trochanteric fractures occurred than neck fractures during the observational period; however, the neck/trochanter ratio increased over time. Simple falls were the most common cause of fracture. About 94% patients were treated surgically with about a 5-day presurgical hospital stay, and the mean hospitalization period was 40.7 days in 2008.
This one-decade survey demonstrated a drastic increase in the number of patients over the course of the decade in Japan. Appropriate treatment and prevention of hip fractures, including the treatment of osteoporosis and more effective interventions for preventing falls, are important issues to address to reduce the burden of this fracture.
Journal of Orthopaedic Science 11/2010; 15(6):737-45. · 0.84 Impact Factor
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Journal of the American Geriatrics Society 09/2010; 58(9):1810-2. · 3.74 Impact Factor
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ABSTRACT: Although many surgical procedures are available for treating osteoporotic vertebral fractures, there have been no comprehensive multicenter surveys in Japan focusing on surgical treatments for these fractures. This study aimed at (1) conducting a retrospective multicenter study to survey surgical treatments performed at referral center hospitals in various regions in Japan and (2) analyzing situations and problems related to the surgical treatments of osteoporotic vertebral fractures in Japanese hospitals.
Among 738 patients who were hospitalized in 13 hospitals in various regions in Japan between 2005 and 2006 for osteoporotic vertebral fractures, 84 patients (11.4%) who underwent spinal surgery were enrolled. These patients were retrospectively analyzed regarding cause of injury, preoperative symptoms, preoperative neurological function, surgical procedures, periods of bed rest, length of hospital stay, and ambulatory status at discharge from hospital.
As to the cause of spinal fracture, 38 patients (45% of the surgical patients) could not identify a specific cause of their spinal fracture. Preoperative neurological motor weakness in legs was observed in 41 (49%). With regard to surgical treatment, posterior spinal reconstruction surgery was performed in 50 patients (60%), vertebroplasty in 26 (31%), anterior reconstruction surgery in 6 (7%), anterior and posterior combined reconstruction surgery in 1, and posterior decompression alone in 1 patient. In all, 70 patients (83.3%), whose periods of hospital stay averaged 52.8 days, could walk by themselves at the time of discharge; 14 (16.7%), whose periods of hospital stay averaged 44.7 days, could not walk by themselves at the time of discharge.
Even after a large variety of surgical procedures were tried to treat osteoporotic vertebral fractures and long hospital stays, about 17% of the patients were unable to walk by themselves at the time of discharge from hospital.
Journal of Orthopaedic Science 05/2010; 15(3):289-93. · 0.84 Impact Factor
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ABSTRACT: The status of hip fracture incidence and treatment is well known through nationwide surveys in Japan. However, there have been no similar studies on spine fractures. Therefore, we investigated current medical practices for them.
Altogether, 1200 hospitals were randomly selected for the survey with consideration of region and hospital characteristics. Questionnaire items included the number of hospitalized spine patients, imaging test implementation, type of conservative treatment, use of open surgery and vertebroplasty, and the number of these procedures performed in 2005.
Responses were received from 473 hospitals. On the day of response, there were 14 372 hospitalized orthopedic patients (average 32.8/hospital). Among them were 1403 spine fracture patients (3.1/hospital), accounting for 13.5% of orthopedic patients. Of them, 91.9% received conservative treatment. The mean percentage of spine fracture patients who were hospitalized was 39.5%. The most reliable imaging test was said to be magnetic resonance imaging. Casting or bracing was used in most of the institutions. The most common analgesic treatment was oral nonsteroidal antiinflammatory drugs. Open surgery and vertebroplasty were conducted for spine fractures in the elderly at 26.5% and 16.3% of hospitals, respectively. In these hospitals, 624 and 257 patients underwent open surgery and vertebroplasty, respectively, in 2005.
In Japan, more than 90% of elderly patients hospitalized with spine fractures received conservative treatment. Surgical treatment, either open surgery or vertebroplasty, was performed at 30% of the hospitals. This study provides basic data that will contribute to planning improvements in spinal fracture treatment in the elderly.
Journal of Orthopaedic Science 01/2010; 15(1):79-85. · 0.84 Impact Factor
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ABSTRACT: Two case-control studies were designed to investigate the contribution of the geometry and bone mineral density (BMD) of the proximal femur to bone strength in Japanese elderly women. We also investigated whether clinical CT is useful to assess the risk of hip fracture. Subjects in the neck fracture study included 20 Japanese women with neck fracture (age: mean+/-SD; 80.1+/-4.5 years old) and 20 age-matched control women (79.2+/-2.6 years old). Subjects in the trochanteric fracture study included 16 Japanese women with trochanteric fracture (82.6+/-5.0 years old) and 16 age-matched control women (80.8+/-3.8 years old). CT examination of the proximal femur was performed between the date of admission and the date of surgery. The CT scanners used were an Aquillion 16 (Toshiba) and Somatom 64 (Siemens); the scanning conditions including spatial resolution and scanning energy were adjusted, and the same type of reference phantom containing hydroxyapatite was used. QCT PRO software (Mindways) was used to analyze data for BMD, geometry, and biomechanical parameters. Both the neck and trochanteric fracture cases had significantly lower total and cortical BMD, a significantly smaller cortical cross-sectional area (CSA), and a larger trabecular CSA. Both had significantly thinner cortex and smaller distance to center of bone mass, and women with trochanteric fracture had a significantly smaller cortical perimeter in the cross-sectional femoral neck. Women with neck fracture had a longer hip axis length (HAL) and women with trochanteric fracture had a significantly larger neck-shaft angle (NSA). Both groups had significantly lower cross-sectional moment of inertia (CSMI), and only women with neck fracture had a significantly higher buckling ratio (BR) compared to their respective controls. According to the multiple logistic regression analysis, women with neck fracture had a significantly longer HAL, lower CSMI, and higher BR, and women with trochanteric fracture had a significantly smaller cortical CSA of the femoral neck. We conclude that clinical CT may be useful for the assessment of the risk of neck and trochanteric fracture.
Bone 10/2009; 46(2):453-7. · 4.02 Impact Factor
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ABSTRACT: Hip fractures among the elderly are a worldwide problem. The objective of this study was (1) to confirm whether or not differences in bone strength are reflected in the proximal femur finite element (FE) model constructed from CT images of healthy subjects and osteoporosis patients, and (2) to investigate the effect of loading angle direction on bone fractures. The results from comparison of bone strength between the fracture group, fragile group (osteoporosis patients with no fracture after falling), and healthy group showed that differences in bone strength were definitely reflected in this FE model. Furthermore, the relationship between the loading direction and fracture load value was significant in all groups in the age-adjusted general linear model, and the model made from the trochanteric fracture patients was more sensitive to loading direction than those from cervical neck fracture. No significant differences were observed in the age-corrected comparison of DXA Neck BMD, Wards BMD, and total BMD in these two groups. The difference in the trochanteric BMD showed a trend of low bone density in the trochanteric fracture group. There is thus a possibility that the bone density at this location is implicated in the fragility under certain loading directions.
Medical Engineering & Physics 09/2009; 31(9):1134-9. · 1.62 Impact Factor
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Junichi Yamauchi,
Shinji Takai,
Rie Matsushima-Nishiwaki,
Seiji Adachi,
Chiho Minamitani,
Hideo Natsume,
Jun Mizutani,
Takanobu Otsuka,
Jun Takeda, Atsushi Harada,
Osamu Kozawa,
Haruhiko Tokuda
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ABSTRACT: We previously reported that basic fibroblast growth factor (FGF-2) stimulates the release of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates VEGF release. In addition, p70 S6 kinase activated by FGF-2 negatively regulates VEGF release via SAPK/JNK. In the present study, we investigated the effects of tacrolimus (FK506) and cyclosporine A, well-known immunosuppressants, on the FGF-2-induced VEGF release in these cells. Tacrolimus, but not cyclosporine A which alone had no effect on VEGF basal levels, significantly enhanced FGF-2-stimulated VEGF release. Tacrolimus markedly enhanced FGF-2-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p44/p42 MAP or p38 MAP kinases. SP600125, a specific inhibitor of SAPK/JNK, reduced the amplification by tacrolimus of the FGF-2-induced VEGF release. The FGF-2-induced phosphorylation of p70 S6 kinase was suppressed by tacrolimus. These results strongly suggest that tacrolimus enhances FGF-2-stimulated VEGF release via up-regulation of SAPK/JNK through modulating p70 S6 kinase in osteoblasts.
International Journal of Molecular Medicine 03/2009; 23(2):267-72. · 1.98 Impact Factor
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ABSTRACT: We examined the influence of high fall-related self-efficacy on falls due to dissociation with activities of daily living (ADL) among elderly women in nursing homes.
We enrolled 72 female nursing home residents who were 70 years old or over and who scored 18 or higher on the Mini-Mental State Examination (MMSE). Subjects were classified into three groups based on the relationship between ADL and fall-related self-efficacy derived from a scattergram of the Functional Independence Measure (FIM) motor items and Falls Efficacy Scale (FES). The three groups were: group I which had low ADL and high fall-related self-efficacy (n=25); group II which had high ADL and low fall-related self-efficacy (n=30); and group III which had a correlation of ADL and fall-related self-efficacy in the 95% confidence interval (n=17). Then, we investigated the incidence of falls and the number of falls after 6 months in the three groups. The risk factor of falls was also investigated using multiple logistic regression analysis.
The incidence and number of falls were significantly different in the three groups after 6 months. Moreover, the incidence of those falling was significantly different between group I and group III. The occurrence of falls was also significantly related with a past history of falls, FES, and group I which had low ADL and high fall-related self-efficacy.
These findings suggest that the risk of falling increases in the presence of excessive fall-related self-efficacy dissociated from ADL.
Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 01/2009; 46(5):428-35.
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ABSTRACT: We have previously reported that transforming growth factor-beta (TGF-beta) stimulates the synthesis of vascular endothelial growth factor (VEGF) through p44/p42 mitogen-activated protein (MAP) kinase, p38 MAP kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In order to investigate whether Rho-kinase is involved in the TGF-beta-stimulated VEGF synthesis in these cells we examined the effects of Rho-kinase inhibitors on the VEGF synthesis. TGF-beta time-dependently induced the phosphorylation of myosin phosphatase targeting subunit (MYPT-1) which is a well known substrate of Rho-kinase. Y27632 and fasudil, Rho-kinase inhibitors, significantly reduced the TGF-beta-stimulated VEGF synthesis as well as the MYPT-1 phosphorylation. Y27632 and fasudil failed to affect the TGF-beta-induced phosphorylation of p44/p42 MAP kinase, p38 MAP kinase or Smad2. On the contrary, Y27632 as well as fasudil markedly suppressed the TGF-beta-induced phosphorylation of SAPK/JNK. Taken together, our results strongly suggest that Rho-kinase regulates TGF-beta-stimulated VEGF synthesis via SAPK/JNK activation in osteoblasts.
Biochemical pharmacology 11/2008; 77(2):196-203. · 4.25 Impact Factor
