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Hiroshi Naka

Publications and source records attributed to Hiroshi Naka.

16 recordsLinked to original sources
PubMed2007

Annual change in bone mineral density in predialysis patients with chronic renal failure: significance of a decrease in serum 1,25-dihydroxy-vitamin D.

Bone disease occurs in the predialysis phase of chronic renal failure (CRF). The aim of this study was to examine how a decrease in renal function affects annual bone mineral density (BMD) changes in predialysis CRF patients and to examine the factors that affect BMD. The BMD of the distal radius in 53 predialysis CRF patients (age, 61.3 +/- 10.8 years; serum creatinine 2.7 +/- 1.2 mg/dl) was measured by peripheral quantitative computed tomography (pQCT) twice with a 1-year interval. The total BMD of the radius significantly decreased over a year (P < 0.001), and both trabecular and cortical BMD showed a significant decrease. Significant positive correlations with BMD changes were found for estimated creatinine clearance (r = 0.375, P < 0.01) and baseline serum 1,25(OH)(2)D (r = 0.434, P < 0.005), indicating that BMD decreased to a greater extent with larger reductions in creatinine clearance and serum 1,25(OH)(2)D. Of several bone metabolic markers examined, baseline serum osteocalcin was significantly positively correlated with annual BMD changes (r = -0.276, P < 0.05). Multiple regression analysis showed that baseline serum 1,25(OH)(2)D (beta = 0.434) was a significant predictor of decreases in total and trabecular BMD (R (2) = 0.188, P < 0.01; and R (2) = 0.207, P < 0.01), independent of other confounding factors. These results indicate that BMD decreases as renal function deteriorates in predialysis CRF patients, and that osteocalcin is a clinically useful marker associated with the decrease in BMD. The serum 1,25(OH)(2)D level is the principal factor affecting BMD of the radius, suggesting that supplementation with an active form of vitamin D is of importance for predialysis CRF patients.

Aged↗
PubMed2006

Encapsulation of hydride by molecular main group metal clusters: manipulating the source and coordination sphere of the interstitial ion.

The sequential treatment of Lewis acids with N,N'-bidentate ligands and thereafter with ButLi has afforded a series of hydride-encapsulating alkali metal polyhedra. While the use of Me3Al in conjunction with Ph(2-C5H4N)NH gives Ph(2-C5H4N)NAlMe2 and this reacts with MeLi in thf to yield the simple 'ate complex Ph(2-C5H4N)NAlMe3Li.thf, the employment of an organolithium substrate capable of beta-hydride elimination redirects the reaction significantly. Whereas the use of ButLi has previously yielded a main group interstitial hydride in which H- exhibits micro6-coordination, it is shown here that variability in the coordination sphere of the encapsulated hydride may be induced by manipulation of the organic ligand. Reaction of (c-C6H11)(2-C5H4N)NH with Me3Al/ButLi yields [{(c-C6H11)(2-C5H4N)N}6HLi8]+[(But2AlMe2)2Li]-, which is best viewed as incorporating only linear di-coordination of the hydride ion. The guanidine 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine (hppH) in conjunction with Me2Zn/ButLi yields the micro8-hydride [(hpp)6HLi8]+[But3Zn]-.0.5PhMe. Formation of the micro8-hydride [(hpp)6HLi8]+[ButBEt3]- is revealed by employment of the system Et3B/ButLi. A new and potentially versatile route to interstitial hydrides of this class is revealed by synthesis of the mixed borohydride-lithium hydride species [(hpp)6HLi8]+[Et3BH]- and [(hpp)6HLi8]+[(Et3B)2H]- through the direct combination of hppLi with Et3BHLi.

Journal Article↗
PubMed2006

[Metabolic markers of bone--post-guideline].

Metabolic markers of bone are common clinical parameters for the evaluation of the pathophysiologic conditions and efficacy of the treatment, although they are not helpful for differential diagnosis of osteoporosis. The guideline published officially is helpful for practitioners and non-experts in the field. The distributions of urinary NTX and bone specific alkaline phosphatase are essentially same between primary osteoporotic postmenopausal women less than 70 years old and those over 70 years. No differences were found in the other metabolic markers between these groups. Although clinical evidence for patients over 85 years old is not enough, we do not have to think of age in the clinical application of metabolic markers of bone, if renal functions are within normal ranges.

Aged↗
PubMed2005

Effects of pubertal development, height, weight, and grip strength on the bone mineral density of the lumbar spine and hip in peripubertal Japanese children: Kyoto kids increase density in the skeleton study (Kyoto KIDS study).

The effects of growth and pubertal development on the bone mineral density (BMD) of the lumbar spine and hip in peripubertal Japanese children were studied as a basis for evaluating the effects of modifiable factors on bone mass gain. The study comprised bone mass measurements in the lumbar spine (L2-4), femoral neck, and total hip using dual-energy X-ray absorptiometry as well as body size measurements and detailed interviews on medical history and pubertal status. The subjects were 404 first-grade students in three junior high schools (129 boys and 275 girls, mean age 12.8 +/- 0.3 years) with no diseases or medication that would affect bone metabolism. BMD at each site showed an increasing trend with physical growth and sexual maturity. Significant positive correlations were observed between BMD at every skeletal site and height, weight, and grip strength in pre- and postpubertal boys and girls. In multiple regression analyses, pubertal development had a significant positive independent effect on BMD at every skeletal site in girls, but not in boys. Physical and pubertal development showed major effects on BMD, but the magnitude of these effects differed in boys and girls, even if they were of the same age. We conclude that confounding factors due to physical and pubertal development should be taken into consideration in different ways for boys and girls in investigations on the effects of environmental or behavioral factors on bone mass acquisition in peripubertal children.

Adolescent↗
PubMed2005

[Bisphosphonates and bone quality].

The clinical use of drugs, which modestly increase bone mineral density, but have sufficient effects on the fracture prevention comparable to bisphosphonates, focuses on the research of the quality of the bone. Clinical investigations using micro CT, Fourier transform infrared imaging spectroscopy, quantitative computerized tomography, and/or other new modalities which support bisphosphonate treatment do not show any quality problems of the bone. In the clinical setting, evaluation of bone quality is very limited, even in the evaluation of patients treated with bisphosphonate, except evaluation by the changes of metabolic markers of bone. The new modalities such as low radiation-dose CT, sensitive MRI or ultra sonography are expected for the clinical evaluation of the changes of bone quality.

Animals↗
PubMed2005

[Epidemiological characteristics and trends of bone mass gain in physical activity intervention trials for children and adolescents].

High-impact or weight-bearing physical activities have positive effects on bone mass gain in children and adolescents from the findings of the physical activity intervention trials for them. These physical activity trials have been relatively short term in research design and some of the intervention trials had small numbers of subjects. Significant benefits on bone mass gain in children and adolescents were observed in almost all studies concerning physical activity intervention trials, although there was considerable variability in magnitude. The discrepancies in findings might relate to the characteristics of participants (sex, age, maturity); the characteristics of the intervention (intensity, frequency, duration); and the bone region assessed (cortical vs. trabecular). In current research on bone mass gain in children and adolescents, there is a lack of data about the effects of different types of physical activity, the long-term effects of physical activity during growth, and the interaction between pubertal development and physical activity. The results of this study call for a further accumulation of evidence about the effects of physical activity to promote bone health in children and adolescents.

Adolescent↗
PubMed2005

[Acute response of serum PTH and bone markers after injection of 1alpha,25 (OH)2D3 and 22-oxacalcitrol in hemodialysis patient].

Time-course changes of serum PTH and various bone markers were compared after injection of 1alpha,25 (OH)(2)D(3) with that of 22-oxacalcitriol (OCT) in hemodialysis patients. Five patients (M/F; 3/2, mean ages of 61.6 years) were enrolled into the present study. Oral administration of vitamin D(3) derivatives was stopped at least one week before initiation of vitamin injection. After 1 week of single intravenous injection of OCT (5 microg), 1alpha,25 (OH)(2)D(3) (0.5 microg) was followed. Serum levels of intact PTH, intact osteocalcin, bone alkaline phosphatase, cross-linked N-telopeptides of type I collagen, calcium, and phosphate were measured before, 24h, and 48 h after injections of vitamin D(3) derivatives. Significant difference did not exist in time-course changes of serum PTH, any of bone markers, calcium and phosphate between after OCT and 1alpha,25 (OH)(2)D(3) injection. In conclusion, the present study may not support the presence of significant direct effect of vitamin D(3) derivatives on bone metabolism in hemodialysis patients.

Aged↗
PubMed2004

Regio- and chemoselective direct generation of functionalized aromatic aluminum compounds using aluminum ate base.

A regio- and chemoselective direct method for generation of functionalized aromatic aluminum compounds through deprotonative directed ortho-alumination using triisobutyl(tetramethylpiperidino)aluminate (iBu3Al(TMP)Li), prepared by mixing of triisobutylaluminum (iBu3Al) and lithium tetramethylpiperidide (LTMP) in THF, has been developed. Deprotonative alumination of various functionalized benzenes with the use of iBu3Al(TMP)Li proved effective for the direct generation of various ortho-functionalized aluminum aromatic and heteroaromatic derivatives, particularly those with electrophilic functional groups such as cyano, amide, and halogen. Direct alumination, followed by electrophilic trapping (with I2), provided a convenient preparative method for 1,2- or 1,2,3-multisubstituted aromatic compounds. The functionalized aromatic aluminate intermediate also was found to undergo copper- and palladium-catalyzed C-C bond-forming reactions very efficiently and highly regio- and chemoselectively.

Journal Article↗
PubMed2004

The clinical significance of serum osteocalcin and N-terminal propeptide of type I collagen in predialysis patients with chronic renal failure.

Several new serum markers for bone metabolism have recently become available and are being applied to clinical practice. Their clinical usefulness in predialysis patients with chronic renal failure (CRF), however, has not yet been determined. Serum levels of three bone formation markers-bone alkaline phosphatase (BAP), osteocalcin (OC), and N-terminal propeptide of type I collagen (PINP)-and three bone resorption markers-type I collagen cross-linked N-telopeptide (NTx), deoxypyridinoline (DPD), and pyridinoline (PYD)-were measured simultaneously in 85 predialysis CRF patients (serum creatinine 3.5 +/- 1.9 mg/dl, 61.0 +/- 10.9 years old, 54 males and 31 females, 36 diabetics and 49 nondiabetics) to examine the relationships between these markers and bone mineral density (BMD) of the distal radius, as measured by peripheral quantitative computed tomography (pQCT). Trabecular BMD, which is strongly affected by bone metabolism, was significantly negatively correlated with each of the bone formation markers (r=-0.341, p=0.0016, for OC; r=-0.314, p=0.0036, for PINP; r=-0.238, p=0.0315, for BAP), but there was no significant correlation between BMD and any of the bone resorption markers. In multivariate regression analyses (adjusted by age, sex, presence of diabetes, glomerular filtration rate, intact parathyroid hormone, calcium, phosphate, and 1,25-dihydroxyvitamin D), OC and PINP were significantly associated with a decrease in BMD, but BAP was not. In conclusion, we demonstrated that in predialysis CRF patients, BMD of the distal radius, particularly of trabecular bone, is associated with serum OC and PINP levels. OC and PINP are suggested to be possible parameters for the clinical evaluation of the effect of bone metabolism on BMD.

Alkaline Phosphatase↗
PubMed2004

Significance of serum CrossLaps as a predictor of changes in bone mineral density during estrogen replacement therapy; comparison with serum carboxyterminal telopeptide of type I collagen and urinary deoxypyridinoline.

The newly developed Elecsys Beta-CrossLaps/serum assay measures C-terminal telopeptide of type I collagen and has thus been proposed as a reliable serum marker for bone resorption. We investigated its usefulness for monitoring the therapeutic effect of estrogen replacement therapy on bone turnover and bone mineral density (BMD) in patients with postmenopausal osteoporosis. Serum Beta-CTx decreased by 43.2% +/- 9.2% (mean +/- SD), and 55.1% +/- 7.0% at 3 and 6 months, respectively, after initiation of estrogen replacement therapy (ERT), which was significantly greater than the respective value of urinary excretion of deoxypyridinoline (DPD) (27.8% +/- 4.1%, 34.1% +/- 4.9%, respectively) or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) assay (14.5% +/- 4.1%, 13.1% +/- 5.0%, respectively). The percent reduction in serum Beta-CTx at 1, 3, and 6 months after initiation of ERT was significantly correlated in a negative manner with the percent increase in spinal BMD at 6 months. Further, ROC analysis to determine the significance of the percent change in bone resorption markers after 3 months of ERT in predicting the gain in spine BMD after 6 months suggested that serum Beta-CTx and urinary DPD might provide a more discriminating indicator than serum ICTP. In conclusion, the findings suggest that the Elecsys Beta-CrossLaps/serum assay provides a sensitive, and thus useful, tool for assessing bone resorption state in Japanese patients.

Amino Acids↗
PubMed2004

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↗
PubMed2004

[AOS-100].

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Absorptiometry, Photon↗
PubMed2003

Clinical usefulness of measurements of urinary deoxypyridinoline (DPD) in patients with postmenopausal osteoporosis receiving intermittent cyclical etidronate: advantage of free form of DPD over total DPD in predicting treatment efficacy.

Deoxypyridinoline (DPD) in urine, which reflects systemic bone resorption, is considered useful for assessing the effects of osteoporosis treatment. However, there are various methods of measuring DPD in urine but have been few comparative studies of the effectiveness of these methods. In this study, we investigated 94 postmenopausal women (63 patients administered with intermittent cyclical etidronate (ICE), and 31 control patients) focusing on total DPD and free DPD, measured by high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA), respectively. For other metabolic bone markers, i.e., tartrate-resistant acid phosphatase (TRAP), bone-specific alkaline phosphatase (BAP), and osteocalcin (OC), we also investigated the ability of these markers to predict increases in bone mineral density (BMD), by employing receiver operating characteristic (ROC) analysis in relation to increasing BMD following ICE therapy, and we determined the usefulness of the different metabolic bone markers, using the signal-noise ratio derived from the mean significant change (MSC), which is double the day-to-day coefficient of variation in healthy volunteers. In the same way, we defined a significant change in BMD as double the mean change in BMD for 6 months after the initiation of observation in the control group, and we used this value as the cutoff value for ROC analysis. It was found that the assessment of urinary DPD was useful for assessing the treatment efficacy of ICE, and the assessment of changes at week 12 of therapy was most effective. In order to recognize changes in metabolic bone markers when the MSC is considered as the cutoff value, it is useful to assess the change in total DPD by HPLC. However, in order to predict increases in BMD 6 months or more after the initiation of ICE, it seems more effective to measure free DPD by ELISA. We conclude, therefore, that the measurement of free DPD by ELISA is more useful, especially when treatment efficacy of ICE is clinically predicted in individual patients with osteoporosis.

Aged↗
PubMed2003

Vitamin K(2) (menaquinone 4) reduces serum undercarboxylated osteocalcin level as early as 2 weeks in elderly women with established osteoporosis.

Twenty elderly osteoporotic women with vertebral fracture(s) were randomly allocated to two groups; women in the MK(4) group received calcium with menaquinone 4 (MK(4)) at a dose of 45 mg/day for 2 weeks, and women in the control group received calcium alone for the same period. Serum intact osteocalcin (OC) and undercarboxylated osteocalcin (uc-OC) levels were measured by immunoradiometric assay and enzyme immunoassay, respectively, at baseline and on the 7th and 14th days following the start of the treatment. There were no differences in the baseline data including age, weight, phylloquinone, menaquinone 4, menaquinone 7, OC, and uc-OC levels between the MK(4) group and the control group. Administration of MK(4) significantly raised the MK(4) level from 0.20 +/- 0.10 (mean +/- SE) pg/ml to 15.09 +/- 5.62 pg/ml ( P < 0.04), and reduced serum uc-OC levels from 2.80 +/- 0.93 ng/ml to 1.76 +/- 0.56 ng/ml ( P < 0.05) at the end of the study, respectively. No significant changes in these levels were observed in the control group. Serum OC levels were stable during the period in both groups. In this randomized prospective study, the MK(4) group shows a reduction in the serum uc-OC level within 2 weeks without any significant change in OC, suggesting that the uc-OC is changed to carboxylated OC. This early effect of MK(4) on bone metabolism may be estimated by the measurement of serum uc-OC in elderly osteoporotic women with vertebral fractures.

Aged↗
PubMed2002

[Effect of alfacalcidol on bone and calcium metabolism in elderly women].

Oral administration of active vitamin D3 can reduce the loss of bone mass and the incidence of fractures in patients with osteoporosis in Japan. We conducted a prospective study to confirm the effects of 1 alpha(OH)D3 (Alfacalcidol, Alfarol Chugai Tokyo) on bone and calcium metabolism in elderly women with osteoporosis. Enrolled in the present study were 16 elderly osteoporosis women aged 72.6 +/- 4.5 years to whom 1 microgram of 1 alpha(OH)D3 was administered daily. Fasting blood and urine were obtained at baseline, 1 week, 4 weeks, 12 weeks and 24 weeks after the treatment. Monitored parameters were vitamin D metabolites, intact-PTH, bone alkaline phosphatase (BAP), osteocalcin (OC), deoxypyridinoline (DPD) and pyridiuium crosslinked type I collagen telopeptides (CTx). Serum 1 alpha, 25(OH)2D and PTH levels were significantly increased (p < 0.01) and decreased (p < 0.05), respectively at 1 week after commencing administration. There was a significant decrease of DPD (p < 0.05) at 12 weeks after commencing administration compared to the baseline levels. Serum levels of BAP and OC were found elevated at 1 week, and decreased at 12 weeks. In conclusion, the present study clinically confirmed that 1 alpha(OH)D3 stimulates bone formation in vitro. Long-term administration of 1 alpha(OH)D3 indirectly suppressed bone resorption through the suppression of parathyroid function in the elderly.

Aged↗