Biomedical subjects

M Shiraki

Publications and source records attributed to M Shiraki.

At least 55 records · Page 3Linked to original sources

PubMed1998

Saccharated ferric oxide-induced osteomalacia in Japan: iron-induced osteopathy due to nephropathy.

Saccharaed ferric oxide (SFO)-induced osteomalacia develops when excessive SFO infusions are administrated to patients with anemia for prolonged periods for a few years. The small particles and almost neutral saccharide of SFO filter through the glomerular tufts into the renal tubules, resulting in impairment of proximal renal tubular function, particularly renal reabsorption of phosphate and 1alpha-hydroxylase activity, resulting in decreased serum levels of phosphorus and active vitamin D, both of which lead to development of hypophosphatemic osteomalacia. Furthermore, SFO, at concentrations attainable in serum, exacerbates the osteomalacia by inhibiting bone formation directly. In contrast to itai-itai disease, another iatrogenic osteomalacia due to cadmium nephropathy [44], the proximal renal tubular function impairment induced by SFO is reversible simply by discontinuing the nephrotoxin, which is followed by improvement of all the clinical manifestations, except bone deformities. So far, SFO-induced osteomalacia, that is, SFO-induced osteopathy due to nephropathy, has been reported only in Japan, probably due to the lax surveillance system of the health insurance scheme. All physicians who prescribe SFO should be aware of its severe adverse effects. We hope that such iatrogenic osteomalacia caused by abusive infusion of SFO will never again be reported in our country.

Aged↗

PubMed1998

Bone and calcium metabolism in Werner's syndrome.

In order to compare the bone aging process in Werner's syndrome, a disease characterized by premature aging, and that in natural aging, we have assessed the bone status in a total of 19 cases (11 males and eight postmenopausal females) with Werner's syndrome. The spinal deformity index was determined for a total of 87 vertebral bodies from nine male patients and for a total of 61 vertebral bodies from six female patients. In the male patients, 15 vertebral deformities among 87 vertebrae in seven patients were observed, and the incidences of patients bearing deformity and deformed vertebrae were 77.8 (7/9) and 17.2% (15/87), respectively. In the female patients, the corresponding incidences were 50.0% (3/6) and 4.9% (3/61), respectively. The chi2-values for the incidences of patients bearing deformity and deformed vertebrae in the male and the female patients were 1.25 (P=0.26) and 5.24 (P<0.03), respectively. The metacarpal cortical thickness (MCI) was also measured on hand X-ray films, and the Z scores for MCI in the male (n=9) and female (n=3) patients were -0.8+/-0.3 and -1.6+/-0.3, respectively. This gender-based difference in the MCI was not statistically significant but, the Z scores for MCI in both the males and the females were significantly smaller than those of corresponding age-matched controls (P<0.05 and 0.01, respectively). The serum levels of calcium, intact PTH, 25-OH vitamin D and 1,25(OH)2 vitamin D in three male and three female Werner's syndrome patients were within the reference ranges with one exception. The serum intact osteocalcin levels in the male (2.2+/-0.6 ng/ml) and female (2.6+/-0.8 ng/ml) patients were lower than the age-matched control values (P<0.05 for males) and the postmenopausal control values (P<0.05 for females). In conclusion, the incidence of spinal bone deformity was higher in males with Werner's syndrome than that in female patients. The cortical bone thickness decreased in both the male and the female patients. A low serum intact osteocalcin level was a characteristic finding in the male and in post-menopausal Werner's syndrome, so that the bone changes such as vertebral fracture incidence and the serum intact osteocalcin level in Werner's syndrome may differ from those in normal aging in the general population.

Adult↗

PubMed1998

[Genetic studies in osteoporosis].

Osteoporosis is one of the complex disease which has many responsible fractors to develop this disease. Among the causative factors for osteoporosis, genetic background is believed as the most important factor for osteoporosis. In 1994, Morrison et al reported their pioneering work looking at the close relationship between VDR genotype and bone mass. This report has generated a considerable amount of interest and conflict. The reasons for these conflicts are depending upon the nature of osteoporosis. Namely, the genetic association to the cause of osteoporosis is polygenic. Furthermore, the contribution of a gene to achieve low bone mass is polyphasic. For example, estrogen-receptor gene polymorphisms may show varied importance in the different stage of women's life span. The environmental factors may interefere the penetration of a gene effect and the presence of the other gene effect may also blunt the effect of the candidate gene. To overcome these difficulties in the research work to search osteoporosis gene, we have pay keen attention to the selections of the method of gene analysis and the subjects. The specific gene marker showed the possibility to predict the effect of the treatment of osteoporosis. This may indicate the marker gene itself or the other gene(s) linked with this marker gene regulate the biological response to the treatment. So, gene markers may utilize not only in the field of epidemiological studies but also in clinical practice in near future.

Genetic Linkage↗

PubMed1998

[Vitamin K2].

Vitamin K2 is a known vitamin to promote post-translational modification of vitamin K-dependent protein such as osteocalcin and blood coagulation factors. The effects of vitamin K2 on cortical bone mineral density in osteoporosis has been shown in the phase III DBT trial which had been reported several years ago. However, until now there is no available data regarding to the effect of vitamin K2 on vertebral bone mineral density (LBMD) and on fracture prevention. Thus, a two years randomized open trial to examine the effects of vitamin K2 on LBMD and the fracture prevention in a total of 167 osteoporotic patients had been carried out. The LBMD in vitamin K2 treated group was maintained for 2 years while, that in the control group was deceased to -3% during 2 years observation. The vertebral fracture incidence in the control group was 0.212 +/- 0.038 events/year and that in the treated group was 0.098 +/- 0.029 (p = 0.0186). Vitamin K2 treated group showed significantly lower Glu-osteocalcin level suggesting that vitamin K2 contributed to increase in post-translational modification of osteocalcin. When the treated group was divided into two groups: Group 1 showed low serum Glu-osteocalcin level and Group 2 maintained high Glu-osteocalcin level despite vitamin K2 administration. The LBMD in group 1 significantly higher than that in the Group 2. This may indicate that sufficient tissue supply of vitamin K2 is the limiting factor to increase in LBMD. Furthermore, patients with Apo E4 phenotype showed less response in LBMD comparing to that in the patients without Apo E4. In conclusion, vitamin K2 is effective to maintain trabecular BMD in osteoporosis and effectively prevent future fracture. However, some part of the patients didn't respond to vitamin K2 treatment. Therefore, we have to develop the more practical way(s) to predict the effectiveness of vitamin K2 treatment in osteoporosis.

Bone Density↗

PubMed1997

Identification of CFDD (common regulatory factor for DNA replication and DREF genes) and role of its binding site in regulation of the proliferating cell nuclear antigen gene promoter.

The Drosophila proliferating cell nuclear antigen (PCNA) gene promoter contains at least three transcriptional regulatory elements, the URE (upstream regulatory element), DRE (DNA replication-related element), and E2F recognition sites. In nuclear extracts of Drosophila Kc cells, we detected a novel protein factor(s), CFDD (common regulatory factor for DNA replication and DREF genes) that appeared to recognize two unique nucleotide sequences (5'-CGATA and 5'-CAATCA) and bind to three sites in the PCNA gene promoter. These sites were located at positions -84 to -77 (site 1), -100 to -93 (site 2) and -134 to -127 (site 3) with respect to the transcription initiation sites. Sites 2 and 3 overlapped with DRE and URE, respectively, and the 5'-CGATA matched with the reported recognition sequence of BEAF-32 (boundary element-associated factor of 32 kDa). Detailed analyses of CFDD recognition sequences and experiments with specific antibodies to DREF (DRE-binding factor) and BEAF-32 suggest that CFDD is different from DREF, UREF (URE-binding factor) and BEAF-32. A UV cross-linking experiment revealed that polypeptides of approximately 76 kDa in the nuclear extract interact directly with the CFDD site 1 sequence. Transient expression assays of chloramphenicol acetyltransferase (CAT) in Kc cells transfected with PCNA promoter-CAT fusion genes carrying mutations in CFDD site 1 and examination of lacZ expression from PCNA promoter-lacZ fusion genes carrying mutations in site 1, introduced into flies by germ line transformation, revealed that CFDD site 1 plays an important role for the promoter activity both in cultured cells and in living flies. In addition to the PCNA gene, multiple CFDD sites were found in promoters of the DNA polymerase alpha and DREF genes, and CFDD binding to the DREF promoter was confirmed. Therefore, CFDD may play important roles in regulation of Drosophila DNA replication-related genes.

Amino Acid Sequence↗

PubMed1997

1-alpha-Hydroxyvitamin D3 treatment decreases bone turnover and modulates calcium-regulating hormones in early postmenopausal women.

50 Japanese women within 10 years after menopause (mean age 52.5 years) were studied to determine the effects of 0.75 microgram of 1-alpha-hydroxyvitamin D3 [1-alpha-(OH)D3] with calcium (150 mg/day) (treated group: N = 25) and calcium only (control group: N = 25) for 12 months on bone mass and metabolism. Their L2-4 BMD measurements were 1.5 SD below the mean value of Japanese young, normal women. L2-4 BMDs increased significantly in the treated group (+2.1%; p < 0.01), but decreased significantly in controls (-2.1%; p < 0.01). Although serum calcium and creatinine remained unchanged in both groups, phosphorus levels increased significantly in the treated group (p < 0.01). Urinary calcium/creatinine (Cr) increased in both groups. Urinary pyridinoline/Cr and deoxypyridinoline/Cr decreased significantly in the treated group (p < 0.05), but not in the control group. Serum osteocalcin levels remained unchanged in both groups. Intact parathyroid hormone levels decreased significantly (p < 0.05) and calcitonin levels significantly increased in the treated group (p < 0.05), but these changes were not observed in the control group. These data clearly demonstrate that 0.75 microgram of 1-alpha-(OH)D3 maintained bone mass by reducing bone resorption by modulation of calcium-regulating hormones. Temporarily increased urinary calcium excretion was observed in control group, but did not appear to be effective in modulating bone turnover.

Biomarkers↗

PubMed1997

Estrogen receptor gene polymorphism and bone mineral density at the lumbar spine of pre- and postmenopausal women.

In order to analyze the role of the estrogen receptor (ER) gene allelic polymorphisms on bone mineral density (BMD), 173 pre- and postmenopausal women were divided into four groups according to their menstrual status (group A: premenopausal women; group B: late premenopausal women; group C: postmenopausal women who had menopause for 5 years or less; and group D: postmenopausal women who had menopause for more than 5 years), and the relationship between ER gene polymorphism and lumbar spine BMD, the percent annual change in BMD and biochemical markers were studied. The restriction fragment length polymorphism (RFLPs) were represented as Xx (XbaI) and Pp (PvuII), with upper case and lower case letters signifying the absence or presence of restriction sites, respectively. In group A, the Xx genotype had significantly higher BMD (p < 0.01) than the xx genotype, but the difference was lost in groups B, C, and D. Because the percent annual change in BMD of group A was 0.052% and was not statistically different among genotypes, it is suggested that RFLP by Xba I is closely linked with peak bone mass that was attained during the subject's late thirties. In group B, serum N-region osteocalcin (N-OC) levels and the percent annual change in BMD showed a significantly larger increase than that of group A, indicating postmenopausal bone loss had commenced. Because the N-OC level of the Xx genotype was significantly higher than that of the xx genotype (p < 0.05), and the percent annual change in BMD of the Xx genotype showed a tendency to increase (p = 0.072), it is suggested that the high BMD of the Xx genotype is rapidly lost during menopausal transition. There were no significant relationships between RFLP and BMD in groups C and D, and between RFLP and BMD in groups C and D, and between RFLP by PvuII and BMD. The present study suggests that the Xx genotype is involved in accretion of BMD during young adulthood, but the effect was lost during menstrual transition.

Adult↗

PubMed1997

Purification of an extracellular D-(-)-3-hydroxybutyrate oligomer hydrolase from Pseudomonas sp. strain A1 and cloning and sequencing of its gene.

An extracellular D-(-)-3-hydroxybutyrate oligomer hydrolase was purified from a poly(3-hydroxybutyrate)-degrading bacterium, Pseudomonas sp. strain A1. The purified enzyme hydrolyzed the D-(-)-3-hydroxybutyrate dimer and trimer at similar rates. The enzyme activity was inhibited by a low concentration of diisopropylfluorophosphate. The molecular weight of the hydrolase was estimated to be about 70,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A 10-kbp DNA fragment of A1 was detected by hybridization with the gene (2 kbp) of an extracellular poly(3-hydroxybutyrate) depolymerase from Alcaligenes faecalis. Subsequent subcloning showed that a SmaI-KpnI fragment (2.8 kbp) was responsible for expression of the hydrolase in Escherichia coli and an in vitro transcription-translation system. The expressed protein detected by immunostaining had the same molecular weight as the purified enzyme from A1. The protein band detected in the in vitro transcription-translation system had a molecular size of 72 kDa. The nucleotide sequence of the SmaI-KpnI fragment was determined, and one open reading frame (2,112 nucleotides) was found. It specifies a protein with a deduced molecular weight of 72,876 (704 amino acids). In this sequence, the consensus sequence of serine-dependent hydrolysis, G-X-S-X-G, did not exist.

Amino Acid Sequence↗

PubMed1997

Association of bone mineral density with apolipoprotein E phenotype.

The phenotypes of apolipoprotein E (Apo E) and their relationship with the bone mineral density (BMD) were examined in 284 unrelated postmenopausal Japanese women aged 47-82 years (64.0 +/- 1.0 years, mean +/- SE). The Apo E phenotype was analyzed by the isoelectric focusing method, followed by immunoblotting. The relationship between the Apo E phenotype and the vitamin D receptor (VDR) gene or estrogen receptor (ER) gene genotypes was also studied in the same population. The Apo E phenotypic frequencies in our population were 9.9% for E3/2, 66.5% for E3/3, 1.8% for E4/2, 19.7% for E4/3, and 2.1% for E4/4. We classified these phenotypes into three categories: Apo E4-/- (E3/2 and E3/3, n = 217, Apo E4 +/- (E4/3 and E4/2, n = 61), and Apo E4+/+ (E4/4, n = 6). The age, body weight, body height, and years since menopause were not significantly different among these three categories. The lumbar BMD values in these three groups were significantly different in the order of E4-/- (0.91 +/- 0.01 g/cm2), E4 +/- (0.85 +/- 0.02 g/cm2), and E4+/+ (0.83 +/- 0.06 g/cm2) (p = 0.031). The same trend was also observed for the Z score of the total BMD (p = 0.022). The serum level of intact osteocalcin in E4+/+ (15.2 +/- 5.7 ng/ml) was higher than in E4-/- (7.7 +/- 0.3 ng/ml) or E4 +/- (7.7 +/- 0.7 ng/ml) (p = 0.004 by analysis of variance). However, there were no other significant differences in the serum or urinary levels of bone turnover markers. Serum cholesterol in the E4+/+ group tended to be higher than in the other two groups (p = 0.05). There were no significant associations of the VDR and ER genotypes with the Apo E4 phenotype. A multivariate linear regression analysis revealed Apo E4 to be a significant, independent predictor of the Z score of the lumbar BMD. The effect of the Apo E4 allele on the Z score of the lumbar BMD (-0.493 +/- 0.152) was not significantly different from that in the AAB of VDR (-0.616 +/- 0.225) or PPxx of ER (-0.785 +/- 0.314). In conclusion, the Apo E4 allele is associated with a low bone mass in postmenopausal Japanese.

Aged↗

PubMed1997

Effect of 1 alpha-hydroxyvitamin D3 on loss of bone mineral density immediately after artificial menopause.

To evaluate the effects of 1 alpha-hydroxyvitamin D3 (1 alpha(OH)D3), a series of clinical trials, preventive and therapeutic, were performed in an open label manner in women immediately after oophorectomy. The series included a total of 121 oophorectomized subjects, whose lumbar bone mineral density (L2-4BMD) was followed by the use of dual energy X-ray absorptiometry. (1) Preventive trial: 61 women who had undergone premenopausal bilateral oophorectomy, were divided into 3 groups (Group C: control; Group L: 0.25 micrograms 1 alpha (OH)D3/day; Group H: 0.50-0.75 micrograms 1 alpha (OH)D3/day). The changes in BMD and chemical indices were followed up for one year. (2) Therapeutic trial: the trial included 60 premenopausally oophorectomized subjects having L2-4BMD lower than the normal control level minus 1SD which has been reported in age-matched normal Japanese women. These subjects were divided into 3 groups and treated in the same way as in the preventive trial. In the preventive trial, L2-4BMD decreased by 8.2%, 6.5% and 4.5% in groups C, L and H, respectively, at 12 months of treatment, whereas in the therapeutic trial, L2-4BMD decreased by 3.6%, 3.2% and 0.8% in the groups C, L and H, respectively, at 12 months of treatment. In conclusion, 1 alpha(OH)D3 was found to be effective both to prevent the bone loss subsequent to bilateral oophorectomy and improve low bone mass after oophorectomy.

Bone Density↗

PubMed1996

Association of bone mineral density with polymorphism of the estrogen receptor gene.

PvuII and XbaI restriction fragment length polymorphisms (RFLPs) of the estrogen receptor (ER) gene and its relation to bone mineral density (BMD) were examined in 238 postmenopausal healthy women aged 45-91 years (66.3 +/- 0.6 years, mean +/- standard error of the mean [SEM]) in Japan. The RFLPs were represented as Pp (PvuII) and Xx (XbaI), with capital letters signifying the absence of and small letters the presence of restriction sites. In the PPxx genotype (n = 18), Z score values of BMD were significantly lower than those for other genotypes (n = 220) (lumbar spine, -0.746 vs. -0.065 [p = 0.022]; total body, -0.482 vs. 0.308 [p = 0.002]). We classified the subjects into three genotypes with allelic haplotype: homozygote of the Px haplotype was expressed as the 11 genotype, heterozygote of the Px haplotype as the 10 genotype, and the one lacking the Px haplotype as the 00 genotype. The PpXx genotype was not included in this analysis because the allelic haplotypes are uncertain. The Px haplotype was associated with a low BMD in postmenopausal women (Z score for the lumbar spine, -0.746 vs. -0.279 vs. 0.083, for the 11, 10, 00 genotypes, respectively [p = 0.029]; Z score for the total body, -0.482 vs. 0.164 vs. 0.427, respectively [p = 0.003]). We suggest that some variation of the ER gene linked to these RFLPs is associated with low BMD and that this at least partly explains the cause of postmenopausal osteoporosis in Japanese women.

Aged↗

PubMed1996

Serum N-terminal osteocalcin is a good indicator for estimating responders to hormone replacement therapy in postmenopausal women.

To estimate the response to hormone replacement therapy (HRT) by bone metabolic markers, 36 patients with postmenopausal osteoporosis or osteopenia were studied to assess the correlation between percent baseline changes in lumbar bone mineral density (BMD) after 12 months and those in various bone metabolic markers after 3, 6, and 12 months of HRT. All the patients were treated with 0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone per day and continued for 12 months. BMD was significantly increased up to 4.19 +/- 0.87% after 6 months and 4.93 +/- 1.27% after 12 months of HRT (p = 0.0001 by analysis of variance). In accordance with this, changes in the levels of osteocalcin (p = 0.041), alkaline phosphatase (p = 0.0001), N-terminal osteocalcin (p = 0.0001), urinary excretion of pyridinoline/Cr (p = 0.0001), and deoxypyridinoline/Cr (p = 0.0001) were significantly decreased, respectively. Among these bone metabolic markers, only the change in the serum N-terminal osteocalcin at 3 months (r = 0.557, p = 0.0022), at 6 months (r = 0.470, p = 0.0184), and at 12 months (r = 0.545, p = 0.0061) significantly correlated with the change in BMD 12 months after HRT. The elution profiles of immunoreactive osteocalcin-related molecules in serum fractionated by reverse-phase high performance liquid chromatography revealed that the N-terminal fragment as well as the intact osteocalcin molecule decreased after 3 months of HRT. These results demonstrate that N-terminal osteocalcin is a suitable predictor for estimating good responders to HRT in postmenopausal women.

Analysis of Variance↗

PubMed1996

Vitamin K2 promotes 1alpha,25(OH)2 vitamin D3-induced mineralization in human periosteal osteoblasts.

The effect of vitamin K on mineralization by human periosteal osteoblasts was investigated in the absence and presence of 1alpha, 25 dihydroxyvitamin D3 (1,25(OH)2D3). Vitamin K1 and K2, but not vitamin K3, at 2.5 microM enhanced in vitro mineralization when cells were cultured with vitamin K for 20 days after reaching confluence in vitro. Vitamin K2 (2-methyl-3-all-trans-tetraphenyl-1, 4-naphthoquinone : menatetrenone) was the most potent of these vitamin K analogs; it slightly inhibited alkaline phosphatase (ALP) activity. Human osteoblasts were mineralized and showed the enhanced ALP activity on treatment with 10(-9) M of 1,25(OH)2D3 for 20 or 25 days after confluence. Vitamin K2 promoted the 1,25(OH)2D3-induced mineralization, but slightly inhibited the 1,25(OH)2D3-induced ALP activity. Moreover, vitamin K2 enhanced the 1,25(OH)2D3-induced osteocalcin accumulation in the cells and the extracellular matrix (cell layer), but inhibited the osteocalcin content in the medium produced by the 1,25(OH)2D3 treatment. However, vitamin K2 alone did not induce osteocalcin production in the human osteoblasts. On Northern blot analysis, osteocalcin mRNA expression on 1, 25(OH)2D3-treated cells was enhanced by vitamin K2 treatment, but vitamin K2 alone did not induce osteocalcin mRNA expression. Warfarin blocked both the 1,25(OH)2D3-induced osteocalcin production and the accumulation in the cell layer, and also blocked the 1, 25(OH)2D3 plus vitamin K2-induced osteocalcin production and the accumulation in the cell layer. The 1,25(OH)2D3-induced mineralization promoted by vitamin K2 was probably due to the enhanced accumulation of osteocalcin induced by vitamin K2 in the cell layer. However, we concluded that the mineralization induced by vitamin K2 alone was due to the accumulation of osteocalcin in bovine serum on the cell layer, since osteocalcin extracted from the cell layer was not identified by specific antiserum against human osteocalcin, which does not cross-react with bovine osteocalcin. These results suggest that the mechanism underlying the mineralization induced by vitamin K2 in the presence of 1,25(OH)2D3 was different from that of vitamin K2 alone, and that osteocalcin plays an important role in mineralization by osteoblasts in vitro.

Adult↗

PubMed1996

Immunolocalization of transforming growth factor-beta in the bone tissue.

Fetal mouse calvarias were cultured in a medium containing fetal calf serum, 1,25(OH)2D3 and parathyroid hormone in 5% CO2 incubator at 37 degrees C for 5 days. The calvarias were then fixed in a buffered paraformaldehyde solution and the periostea were removed. A polyclonal antibody against transforming growth factor-beta (TFG-beta) and a second antibody labeled with fluorescein isothiocyanate were used to detect TGF-beta. As a result, a specific staining was observed only in the shielding zone covered by osteoclasts in the bone resorption lacunae and in the extracellular matrix adjacent to the osteoclasts. These findings suggested the local delivery and possible activation of TGF-beta by osteoclasts in tissue.

Animals↗

PubMed1995

Association of estrogen receptor dinucleotide repeat polymorphism with osteoporosis.

We investigated the association between dinucleotide (thymine-adenine) repeat polymorphism lying upstream of human estrogen receptor (ER) gene and bone mineral density (BMD) as well as biochemical markers for bone metabolism in 144 healthy postmenopausal Japanese women. The genotype was classified into 'A' through 'R' according to the number of the repeats, from 10 to 27. BMD was expressed in Z score (a deviation from the weight-adjusted average BMD of each age using the standard deviation as a unit). The people having genotype C (12 repeats of thymine-adenine) allele (n = 15) had significantly lower Z score of spine BMD (mean +/- SD; -1.11 +/- 1.3 vs. -0.06 +/- 1.2; p < 0.01) and of total body BMD (-0.58 +/- 1.0 vs. 0.31 +/- 0.9; p < 0.01) than those without this genotype (n = 129). They also had significantly higher levels of serum intact osteocalcin, urinary pyridinoline, and urinary deoxypyridinoline. These results suggest that genetic variation at the ER locus may be associated with some determinants for BMD and bone metabolism in postmenopausal women.

Aged↗

PubMed1995

The relation between osteoporosis of the spine and osteoarthritis of the knee. A study using dual energy X-ray absorptiometry and radiographs.

We investigated the relation between osteoporosis of the spine and osteoarthritis of the knee using dual energy X-ray absorptiometry of the lumbar spine to measure bone mineral density and radiographs of the knee in 82 randomly selected females (mean age 77.5 years). Radiographs of the knee were divided into a normal and severe group. The bone mineral density of the severe group was significantly more than that of the normal group.

Absorptiometry, Photon↗

PubMed1995

Basal tail skin temperature elevation and augmented response to calcitonin gene-related peptide in ovariectomized rats.

Hyper-release of calcitonin gene-related peptide (CGRP) plays a direct and pivotal role in the induction of menopausal hot flushes (HFs), in which a drastic increase in skin temperature occurs. However, it is not possible to investigate whether CGRP induces skin temperature increase and whether skin temperature response to CGRP changes and contributes to the occurrence of HFs in postmenopausal women who are in oestrogen deficiency. By using rats' tail skin temperature (TST), a good marker to evaluate skin temperature regulation, we examined the effects of CGRP and calcitonin (3, 10 and 30 micrograms/kg, i.v.) on TST in female rats and further investigated the TST change induced by CGRP (10 micrograms/kg, i.v.) in ovariectomized (OVX) rats compared with that in sham-operated (Sham) rats. We found that CGRP, but not calcitonin, induced a TST increase in a dose-dependent manner and that the TST change induced by CGRP (0.6 +/- 0.2 degrees C for OVX rats vs 0.3 +/- 0.1 degree C for Sham rats, P < 0.05) and also the basal TST (26.0 +/- 0.2 degrees C for OVX rats vs 25.5 +/- 0.1 degree C for Sham rats) were significantly greater in OVX rats (P < 0.05). Furthermore, treatment with oestradiol (30 micrograms/kg, s.c.) for 8 days partially inhibited the augmented TST response to CGRP in OVX rats and almost completely inhibited (P < 0.05) the basal TST elevation, with the concomitant recovery of the serum oestradiol level to that in Sham rats. These results suggest that the augmented skin temperature response to CGRP and the elevation of basal skin temperature that are found in OVX rats, animals which are oestradiol deficient, may also occur in menopausal women and contribute to their HFs.

Animals↗

PubMed1995

[Serum concentration of vitamin K in elderly women with involutional osteoporosis].

Oral administration of vitamin K was reported to increase bone mineral density. However, the possible role of vitamin K in the pathogenesis of osteoporosis still remains unclear. Therefore, we measured the serum concentration of vitamin K1 and K2 (menaquinone-4, 7, 8) in 24 elderly women with osteoporotic vertebral compression fracture and in 36 elderly women without fracture. Major forms of vitamin K present in sera in this study were vitamin K1 and menaquinone-7. On the other hand, serum menaquinone-4 and -8 were undetectable in most women. Serum concentration of menaquinone-7 was significantly lower in women with fracture than in those without fracture (3.29 +/- 3.63 ng/ml vs 6.26 +/- 5.62, mean +/- SD, respectively), while no difference was found in serum vitamin K1 concentration (0.837 +/- 0.620 ng/ml vs 0.820 +/- 0.686, respectively). There was no difference between both groups in background data such as age, body height, body weight, and body mass index, as well as serum level of calcium, inorganic phosphate, creatinine, albumin, and alkaline phosphatase. These results suggest the possibility that deficiency of vitamin K, particularly that of menaquinone-7, is one of the risk factors for developing osteoporosis.

Aged↗