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Biomedical subjects

Masako Ito

Publications and source records attributed to Masako Ito.

At least 37 records · Page 2Linked to original sources

Effect and safety of intermittent weekly administration of human parathyroid hormone 1-34 in patients with primary osteoporosis evaluated by histomorphometry and microstructural analysis of iliac trabecular bone before and after 1 year of treatment.

In order to evaluate the efficacy and safety of intermittent subcutaneous administration of 1-34 N-terminal peptide of human parathyroid hormone (hPTH 1-34), 100 units of hPTH 1-34 was subcutaneously injected once a week for 1 year in ten patients with primary osteoporsis (one male and nine females) with no qualitative abnormality of the bone according to the results of iliac crest biopsy performed previously, followed by a second biopsy after the end of the 1-year administration. Written consent of the patients for participation in the study was obtained. The mean lumbar bone mineral density (LBMD) definitely increased, by 1.8%, 3.4%, and 4.6% after 12, 24, and 48 weeks of hPTH administration, in accordance with previous clinical studies. Histomorphometric analysis after double-tetracycline labeling was completed in six patients (one male and five females) after the exclusion of those who dropped out because of adverse events unrelated to the test drug, or refusal of continuation. Examination of thin hard-tissue sections revealed no qualitative abnormalities of bone tissue or bone marrow cavity, such as osteomalacia, woven bone, or osteitis fibrosa, precluding the contribution of qualitatively abnormal tissue elements to any changes of LBMD in response to hPTH 1-34 administration. Histomorphometric measurement in the second biopsy revealed a tendency for an increase of bone volume, a significant increase of osteoid surface, and a tendency for an increase in other parameters of bone formation, compared with values obtained in the preadministration biopsy. Indices of two-dimensional microstructure obtained by microfocus computed tomography (CT) and results of node-strut analysis indicated improvement of trabecular continuity. In five patients in whom three-dimensional reconstruction images were analyzed, there were significant increases of bone volume and trabecular thickness, and a significant decrease in the trabecular bone pattern factor, a parameter related to the continuity, suggesting an improvement of the three-dimensional trabcular microstructure. Intermittent weekly subcutaneous injections of hPTH (1-34) for 48 weeks increased trabecular bone volume and improved microstructure, without causing the appearance of abnormal bone elements in primary osteoporosis.

Aged↗

[DXA].

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Absorptiometry, Photon↗

[Assessment of bone quality--present and future].

Bone quality including "structural property" and "material property" , which is strongly affected by bone remodeling and has an influence on bone biomechanical property. Structural property means macroscopical geometry, bone size, trabecular microstructure, cortical thickness and cortical porosity. Material property means mineralization, crystal size, collagen and microdamage. Although most of them are analyzed in vitro, in the future, noninvasive assessment of bone quality may help to guide therapy of osteoporosis.

Bone Remodeling↗

Which bone densitometry and which skeletal site are clinically useful for monitoring bone mass?

Long-term precision, as well as reproducibility, is important for monitoring bone mineral density (BMD) alteration in response to aging or therapy. In order to investigate which bone densitometry and which skeletal site are clinically useful for monitoring bone mass, we examined the standardized long-term precision of several bone density measurements in 83 healthy Japanese women. Annual BMD measurements were performed for 5 or 6 years using dual X-ray absorptiometry (DXA) on the lumbar spine, radius (EXP5000) and calcaneus (HeelScan); peripheral quantitative computed tomography (pQCT) on the radius (Densiscan1000); and quantitative ultrasound (QUS) on the calcaneus (Achilles+). The long-term precision error for the individual subject was given by the standard error of estimate (SEE), and the standardized long-term precision was defined as the percentage coefficient of variation (CV%) divided by the percentage ratio of the annual bone-loss rate. Based on the CV% of spinal DXA, speed of sound (SOS) and diaphyseal pQCT showed significantly higher precision than others, while radial ultradistal (UD) DXA and heel DXA showed significantly lower precision. The long-term precision errors of other measurements were statistically the same as that of the spinal DXA. The spinal DXA, the radial DXA, and pQCT at both the distal metaphysis and diaphysis showed high rates of annual bone loss. The radial trabecular BMD (pQCT) was significantly higher than that of spinal DXA. The annual rates of bone loss of QUS and of heel DXA were significantly lower than that of spinal DXA. Taken together, standardized long-term precision was obtained in the spinal DXA and radial pQCT. In conclusion, spinal DXA and radial pQCT were considered the most useful monitoring method for osteoporosis, while QUS was considered less useful.

Absorptiometry, Photon↗

Bone structure and mineralization demonstrated using synchrotron radiation computed tomography (SR-CT) in animal models: preliminary findings.

We investigated the ability of synchrotron radiation computed tomography (SR-CT) to demonstrate trabecular microstructure, detail of trabecular surfaces, and mineralization of bones. Eight rat vertebrae, six rat tibiae, and eight minipig vertebrae were scanned using SR-CT at the synchrotron radiation facility Super Photon ring-8GeV (SPring-8). Images obtained using conventional micro-CT, scanning electron microscopy (SEM), and contact microradiography (CMR) were compared with the SR-CT images. SR-CT showed high image quality without visible partial volume effect. Three-dimensional SR-CT revealed shallow concavities in the bone surface, which were considered to correspond to osteoclastic resorption areas, as well as the connectivity, anisotropy, and shape (rod- or platelike) of trabeculae. Two-dimensional SR-CT showed different density along the surface of the trabecular bone, indicating the degree of bone mineralization. In conclusion, SR-CT seems to be a useful tool for delineating trabecular surfaces, evaluating bone mineralization, and revealing precise trabecular structure.

Animals↗

Reductions in bone turnover, mineral, and structure associated with mechanical properties of lumbar vertebra and femur in glucocorticoid-treated growing minipigs.

The present study was designed to determine the effects of glucocorticoid (GC) on bone turnover, minerals, structure, and bone mechanical properties in minipigs. Six 8-month-old Göttingen minipigs were subcutaneously injected with prednisolone (PN, 0.5 mg/kg body wt (BW)/day, 5 days/week for 26 weeks (Group GC)), 6 were treated with vehicle alone (Group VC), and 4 were sacrificed at start of the study for baseline controls (Group BC). The increase in BW was similar in all groups. PN significantly reduced serum osteocalcin and urinary type-1 collagen N-telopeptide levels at 13 weeks and thereafter, compared with baseline and control, and also reduced serum bone specific alkaline phosphatase levels relative to baseline. At 26 weeks, the longitudinal axis of the lumbar bone and length of femur were smaller in Group GC than Group VC. The total cross-sectional area of femur, but not the lumbar bone, in Group GC was significantly different from Group VC. BMD of the femur, but not L2, measured by DXA, was lower in Group GC than in Groups BC and VC. The cortical shell structure measured by 2D-micro-CT deteriorated and age-dependent increases in trabecular bone structure 3D micro-CT were reduced by PN. PN also caused deterioration of the cortical structure of the mid-femur. In L2 and femur, PN significantly reduced the ultimate load and maximum absorption energy of the femur and L2 compared with Group VC. The structural modulus in Group GC was lower than in Group BC. Regression analyses revealed that bone minerals, bone structure, and chemical markers correlated with mechanical properties of L2 and mid-femur. Our results indicate that PN reduced systemic bone formation and resorption and suppressed the age-dependent increases in bone minerals, structure, and mechanical properties of L2 and mid-femur. Reduced bone turnover seemed to be associated with a reduction in mechanical properties. The growing minipig could be a suitable model of GCs-induced osteoporosis in humans.

Animals↗

Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra.

This study aimed to investigate the effect of long-term suppression of bone resorption by bisphosphonate on the microstructure, accumulation of microdamage, and mechanical properties of trabecular bone. Twenty-nine 1-year-old beagles (15 males, 14 females) were divided into three groups. The control group (CNT) was treated daily with vehicle, and the other two groups were treated with incadronate at a dose of 0.3 mg/kg/day (LOW) or 0.6 mg/kg/day (HIGH) orally for 3 years. After death, the second thoracic vertebra was scanned with microcomputed tomography (micro-CT) and assigned to histomorphometric and microdamage measurements. The fourth lumbar vertebra was mechanically tested by compression. Incadronate concentration in bone was measured in the 11th thoracic vertebra. Micro-CT analysis demonstrated a platelike trabecular structure and increased concave surface of trabeculae in the thoracic vertebra of incadronate-treated groups. Three-year incadronate treatment significantly suppressed trabecular activation rates by 56% in LOW and 67% in HIGH without impairment of mineralization, and increased microdamage accumulation in both incadronate-treated groups. Trabecular bone volume was significantly increased in both LOW and HIGH groups, and vertebral strength was significantly increased in the HIGH group compared with the CNT group. However, intrinsic material properties such as normalized ultimate stress and normalized toughness were reduced in incadronate-treated groups. Incadronate concentration in bone was dose-dependent. This study suggests that long-term suppression of bone remodeling increases microdamage accumulation, but this is not necessarily associated with vertebral fragility because of compensated increase of bone mass and improved microarchitecture.

Animals↗

[Effects of bisphosphonate on trabecular microstructure].

Bisphosphonate is known to be deposited in resorption area. In our small animal study to evaluate the effect of bisphosphonate on trabecular microstructure, micro-CT demonstrated the different trabecular microstructure among the sham, ovariectomized (OVX) rats and the OVX rats which were treated with risedronate (0.1, 0.5, 2.5 mg/kg) or menatetrenone 30 mg/kg, or with the combination of risedronate 0.5 mg/kg and menatetrenone 30 mg/kg. The pattern of change on trabecular microstructure was also different between risedronate and menatetrenone; risedronate maintained trabecular connectivity, whereas menatetrenone thickened the trabeculae. The combination therapy with menatetrenone provided an additional improvement of trabecular microstructure to the single use of risedronate.

Animals↗

[Involvement of Daikou Sunabashi Clinic in home care to home death].

Daikou Sundabashi Clinic provides continuous advanced medical treatment and visiting nursing services for patients with serious diseases till their death at home. The clinic has been involved in home care of 72 patients in total during the period from April 2002 to July 1 of 2003. Of the patients, 40 patients died to date and 71% (32 patients) of them died at home. 49 of the 72 patients (70%) had terminal cancer and mostly required advanced home care. The clinic provides services according to the following principles till the death of the patients: 1. All of our medical staff pool their information and stay in very close communication with one another. 2. The attending physician gives a complete explanation of the patient's condition to his/her family. 3. The staffs respond to emergency calls around the clock using 2 cell phones. Under this very meticulous and fast-response system, seriously ill patient can receive continuous and high-quality treatment at home and die at home even if the family is not adequately capable of providing care.

Aged↗

[Pain control at home in cooperation with hospitals].

At present, many patients heavily dependent on medical care live at home. Therefore, the need for pain control at home is increasing. Within the limits of home care, the method used to control pain control is very important. Here we report 2 cases who need more than 1,000 mg of morphine (converted into oral administration). And we introduce our method for pain control at home. Our method is as follows: 1. Before the patient is discharged from the hospital, we go to the hospital and confirm the patient's condition and pain. 2. If necessary, before the patient is discharged from the hospital, we request to change instruments for home care. 3. We select the best way (instruments, circuits, administration) in consideration of the patients' or their families ADL. 4. When we change a route from oral administration to injection, we let the patient enter the hospital temporarily to adjust the quantity of morphine.

Activities of Daily Living↗

[Method for home parenteral nutrition (HPN) at Daikou Sunadabashi Clinic].

In recent years many patients who have become heavily dependent on medical care live at home. At Daikou Sunadabashi Clinic, we take care of many patients who have malignant tumors, at their homes. They need many medical treatments, so HPN has become a common practice. Here we show our circumstances of HPN. And we introduce our method for HPN. Our method is as follows: 1. Before the patient is discharged from the hospital, we go to the hospital and confirm the patient's condition. 2. We assess the level of training regarding HPN, and select the best way (instruments, circuits, administration) in consideration of the patients' or their families ADL. 3. We select a visiting nurse station 4. and train the visiting nurse in HPN using our manuals. 5. We use an HPN pump. 6. We select a simple way of infusion and adjust it to the patient's condition. In this way, we use HPN easily at home with the aid of a visiting nurse, visiting pharmacist, families, and us.

Activities of Daily Living↗

[Survey on the attitude of families which have taken care of patients until their death at home].

The results of our survey using a questionnaire were as follows: 1. patients' families had a positive attitude toward the patients' death at home, 2. a good communication was established between the nurses from our institution and the patients or their families, 3. the nurses were considered reliable and friendly, 4. for several days or immediately before the patients' death, which was the most severe period for the patients and their families, the patients and their families needed more support from the nurses.

Aged↗

[Involvement of Daikou Sunadabashi Clinic in home care to home death].

Daikou Sunadabashi Clinic provides continuous advanced medical treatment and visiting nursing services for patients with serious diseases till their death at home. The clinic has been involved in home care of 72 patients in total during the period from April 2002 to July 1 of 2003. Of the patients, 40 patients died to date and 71% (32 patients) of them died at home. 49 of the 72 patients (70%) had terminal cancer and mostly required advanced home care. The clinic provides services according to the following principles till the death of the patients: (1) All of our medical staff pool their information and stay in very close communication with one another. (2) The attending physician gives a complete explanation of the patient's condition to his/her family. (3) The staffs respond to emergency calls around the clock using 2 cell phones. Under this very meticulous and fast-response system, seriously ill patient can receive continuous and high-quality treatment at home and die at home even if the family is not adequately capable of providing care.

Aged↗

[Pain control at home in cooperation with hospitals].

At present, many patients heavily dependent on medical care live at home. Therefore, the need for pain control at home is increasing. Within the limits of home care, the method used to control pain control is very important. Here we report 2 cases who need more than 1,000 mg of morphine (converted into oral administration). And we introduce our method for pain control at home. Our method is as follows: (1) Before the patient is discharged from the hospital, we go to the hospital and confirm the patient's condition and pain. (2) If necessary, before the patient is discharged from the hospital, we request to change instruments for home care. (3) We select the best way (instruments, circuits, administration) in consideration of the patients' or their families ADL. (4) When we change a route from oral administration to injection, we let the patient enter the hospital temporarily to adjust the quantity of morphine.

Analgesics, Opioid↗

[Survey on the attitude of families which have taken care of patients until their death at home].

The results of our survey using a questionnaire were as follows: (1) patients' families had a positive attitude toward the patients' death at home, (2) a good communication was established between the nurses from our institution and the patients or their families, (3) the nurses were considered reliable and friendly, (4) for several days or immediately before the patients' death, which was the most severe period for the patients and their families, the patients and their families needed more support from the nurses.

Attitude↗

Vitamin D hormone inhibits osteoclastogenesis in vivo by decreasing the pool of osteoclast precursors in bone marrow.

Previous observations that vitamin D hormone induces the expression of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL), thereby stimulating osteoclastogenesis in vitro, led to the widespread belief that 1alpha,25-dihydroxyvitamin D3 [1a,25(OH)2D3] is a bone-resorbing hormone. Here, we show that alfacalcidol, a prodrug metabolized to 1alpha,25(OH)2D3, suppresses bone resorption at pharmacologic doses that maintain normocalcemia in an ovariectomized (OVX) mouse model of osteoporosis. Treatment of OVX mice with pharmacologic doses of alfacalcidol does not increase RANKL expression, whereas toxic doses that cause hypercalcemia markedly reduce the expression of RANKL. When bone marrow (BM) cells from OVX mice were cultured with sufficient amounts of macrophage colony-stimulating factor (M-CSF) and RANKL, osteoclastogenic activity was higher than in sham mice. Marrow cultures from alfacalcidol- or estrogen-treated OVX mice showed significantly less osteoclastogenic potential compared with those from vehicle-treated OVX mice, suggesting that the pool of osteoclast progenitors in the marrow of vitamin D-treated mice as well as estrogen-treated mice was decreased. Frequency analysis showed that the number of osteoclast progenitors in bone marrow was increased by OVX and decreased by in vivo treatment with alfacalcidol or estrogen. We conclude that the pharmacologic action of active vitamin D in vivo is to decrease the pool of osteoclast progenitors in BM, thereby inhibiting bone resorption. Because of its unusual activity of maintaining bone formation while suppressing bone resorption, in contrast to estrogens that depress both processes, vitamin D hormone and its bone-selective analogs may be useful for the management of osteoporosis.

Animals↗

[Future prospects in bone mineral measurement].

Purposes of bone mineral density (BMD) measurement include making accurate diagnosis of osteoporosis and accurate assessment of fracture risk, assessing intervention threshold, and evaluating effects of treatment. Our final goal is the prevention of fracture avoiding excessive treatment. Investigation concerning the validity of the WHO and Japanese primary osteoporosis criteria has been repeated. Further investigation will clarify the usefulness of quantitative ultrasound, the usefulness of BMD measurement in secondary osteoporosis, and in vivo assessment of bone quality.

English Abstract↗