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Masataka Shiraki

Publications and source records attributed to Masataka Shiraki.

At least 37 records · Page 2Linked to original sources
PubMed2004

Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density.

Low-density lipoprotein receptor-related protein 5 (LRP5) is an important regulator of osteoblast growth and differentiation, affecting peak bone mass in vertebrates. Here, we analyzed whether the LRP5 gene was involved in the etiology of postmenopausal osteoporosis, using association analysis between bone mineral density (BMD) and an LRP5 gene single-nucleotide polymorphism (SNP). Association of an SNP in the LRP5 gene at IVS17-1677C > A (intron 17) with BMD was examined in 308 postmenopausal Japanese women (65.2 +/- 9.6 years; mean +/- SD). The subjects bearing at least one variant A allele (CA + AA; n = 142) had significantly lower Z scores for total body and lumbar BMD than the subjects with no A allele (CC; n = 166) (total body, 0.08 +/- 1.09 versus 0.50 +/- 1.03; P = 0.0022; lumbar spine, -0.42 +/- 1.43 versus -0.02 +/- 1.42; P = 0.013). These findings suggest that the LRP5 gene is a candidate for the genetic determinants of BMD in postmenopausal women, and this SNP could be useful as a genetic marker for predicting the risk of osteoporosis.

Aged↗
PubMed2004

Alfacalcidol reduces accelerated bone turnover in elderly women with osteoporosis.

To evaluate the effects of alfacalcidol on bone turnover in elderly women with osteoporosis, an open-label, prospective, calcium-controlled study was conducted. A total of 80 patients with osteoporosis were divided into two groups: the control group, group C (mean age, 78.0 years), in which patients were given calcium, and group D (mean age, 77.4 years), in which the patients were given alfacalcidol 1 micro g/day together with calcium for 6 months. Calcium regulation, lumbar bone mineral density (LBMD), and markers for bone turnover were assessed. A significant increase in urinary calcium/creatinine ratio (90% increase from baseline at 3 months; P = 0.0083, and 60% at 6 months; P = 0.0091) and a significant decrease in serum parathyroid hormone (30% decrease from baseline at 6 months; P < 0.0001) was observed in group D compared with the corresponding changes in group C. Significant decreases of bone resorption markers (deoxypyridinoline and N-telopeptide) at 6 months (about 15% decrease from the baseline values) were observed in group D compared with the corresponding changes in group C. The changes in bone formation markers (bone-derived alkaline phosphatase and osteocalcin) in group D were significantly different at 6 months (-21.5%; P = 0.0047 and -13.4%; P = 0.0032, respectively) from the values in group C. The magnitudes of the decrease in bone turnover markers were highly correlated with the corresponding baseline values, suggesting that alfacalcidol treatment effectively reduces bone turnover in patients with high bone turnover rates. The LBMD in group D increased by 1.7% and that in group C decreased by 1.6% ( P = 0.0384). The changes in calcium metabolism and LBMD were in good agreement with those in previous reports. Although the changes in bone turnover markers in group D were slight, significant reduction in bone turnover with alfacalcidol treatment, together with the change in calcium metabolism, may account for the effects of alfacalcidol on BMD and on fracture prevention reported previously. In conclusion, alfacalcidol reduces bone turnover in elderly women with high-bone-turnover osteoporosis, and it may have beneficial effects on bone.

Aged↗
PubMed2004

Alendronate reduced vertebral fracture risk in postmenopausal Japanese women with osteoporosis: a 3-year follow-up study.

The risk-reducing effect of alendronate on vertebral fractures has been consistently reported. In a 2-year, randomized, double-blind, active drug-controlled (1 microg alfacalcidol) double-dummy study, we also reported that alendronate (5.0 mg) had a fracture-reducing effect in Japanese patients with preexisting vertebral fractures. The present report describes the risk-reducing effect of alendronate (5.0 mg) for 3 years in postmenopausal osteoporotic patients. The 3-year treatment period consisted of the original 2-year double-blind study followed by a 1-year extension. A total of 170 postmenopausal female patients were involved in the third year; 90 received alendronate and 80 received alfacalcidol. Both efficacy and safety were analyzed in these 170 patients. Vertebral fracture was determined by quantitative morphometry, and vertebral bone mineral density (BMD) was measured by the DXA method (dual-energy X-ray absorptiometry). The primary efficacy endpoint was the incidence of vertebral fracture, excluding fracture cases that occurred in the first 6 months after treatment initiation. The cumulative incidence of vertebral fracture at 3 years was 7.8% (7/90) in the alendronate group and 18.8% (15/80) in the alfacalcidol group, indicating a significantly reduced risk of fractures in the alendronate group (relative risk = 0.41, 95% CI = 0.18-0.97). Lumbar spine BMD increased by 9.2% in the alendronate group (n = 26) and by 1.4% in the alfacalcidol group (n = 22) at 3 years. The safety profile of alendronate during 3 years of treatment was similar to that of alfacalcidol. The present study thus demonstrated that treatment with alendronate 5.0 mg for 3 years increased vertebral BMD and reduced the risk of vertebral fractures in Japanese, postmenopausal women with osteoporosis.

Aged↗
PubMed2004

A comparison of incidences of vertebral fracture in Japanese patients with involutional osteoporosis treated with risedronate and etidronate: a randomized, double-masked trial.

To demonstrate the clinical benefit of risedronate at 2.5 mg daily in the treatment of involutional osteoporosis, the effect of risedronate on incidence of vertebral fracture was compared with that of etidronate. A total of 547 patients with one to four vertebral fractures were randomized to receive either treatment with 2.5 mg/day of risedronate or intermittent treatment (treatment of 2 weeks and off period of 10 weeks) with 200 mg/day of etidronate for 96 weeks in a double-masked fashion. All patients received 200 mg calcium supplement daily. Lateral and anteroposterior thoracic and lumbar spine radiographs were obtained at baseline and at 24, 48, 72, and 96 weeks. Cumulative incidence rates of patients who had at least one new or worsening vertebral fracture during the 96-week period were 12.3% for risedronate and 14.2% for etidronate, and it was verified that the fracture prevention effect of risedronate was not inferior to that of etidronate. The incidence rates of fracture during the initial 24-week period were 8.8% for risedronate and 6.0% for etidronate, but the cumulative incidence rate of fracture from 24 to 96 weeks was lower in the risedronate group (3.9%) as compared to the etidronate group (8.7%). Height loss was significantly less in the risedronate group (-0.28 cm) than in the etidronate group (-0.70 cm) after 96 weeks. Decreases in bone resorption markers including urinary total deoxypyridinoline and NTX were significantly greater in the risedronate group than in the etidronate group throughout the treatment period. An improvement of patient QOL was observed in both groups. No significant difference in the incidence of adverse events was observed between the two treatments. Daily oral risedronate (2.5 mg) was shown to provide an effective therapy for involutional osteoporosis in Japanese patients with good tolerability.

Aged↗
PubMed2003

Menopausal hot flash and calciotonin gene-related peptide; effect of Keishi-bukuryo-gan, a kampo medicine, related to plasma calciotonin gene-related peptide level.

OBJECTIVES: The purpose of this study is to investigate relationship of menopausal hot flash and calcitonin gene-related peptide (CGRP). Furthermore, this study evaluated the effect of the Japanese herbal (kampo) medicine Keishi-bukuryo-gan from the aspect of CGRP regulation. METHODS: Plasma CGRP and vasoactive intestinal peptide (VIP) levels were measured during hot flash and CGRP reactivity was studied by cold load test in subjects with/without hot flashes. The effect of Keishi-bukuryo-gan was assessed in comparison with plasma CGRP level. RESULTS: Only plasma CGRP but not VIP significantly elevated at the occurrence of hot flash (P=0.002). Stress by cold load significantly enhanced the over-secretion of CGRP in subjects with flash compared with those without flash (P=0.003) 3 min after the load. Keishi-bukuryo-gan decreased plasma CGRP level in subjects with hot flash. CONCLUSIONS: CGRP but not VIP was mainly related to the occurrence of hot flash. Keishi-bukuryo-gan, Japanese herbal medicine, improves hot flash possibly affecting plasma CGRP level.

Calcitonin Gene-Related Peptide↗
PubMed2003

Association of genetic variation of the RIL gene, encoding a PDZ-LIM domain protein and localized in 5q31.1, with low bone mineral density in adult Japanese women.

Twin and family studies had shown that genetic factors are important determinants of bone mass. Multiple genes might be involved. One candidate gene, the reversion-induced LIM gene ( RIL), is a PDZ and LIM-domain-containing protein and has been localized within the cytokine cluster of chromosome 5 (5q31.1). In a genetic study of 370 adult Japanese women, we investigated the correlation between radial bone mineral density (BMD) and a genetic variation (-3333T-->C) of the 5'-flanking region of RIL gene. A significant association was identified between the RIL variation -3333T-->C and radial BMD ( r=0.15, P=0.003). The variation of the RIL locus may be an important determinant of osteoporosis.

Adult↗
PubMed2003

Association of the -381T/C promoter variation of the brain natriuretic peptide gene with low bone-mineral density and rapid postmenopausal bone loss.

Osteoporosis is believed to result from interplay among multiple environmental and genetic determinants, including factors that regulate bone-mineral density (BMD). Recent quantitative trait locus analysis in human suggested a possible involvement of chromosomal region 1p36.2-p36.3 for determination of BMD. The brain natriuretic peptide (BNP, also named NPPB) gene lies within this candidate region for BMD determination. Overexpression of the BNP resulted in skeletal overgrowth in transgenic mice. Association analysis between nucleotide variations of the BNP gene and radial BMD in 378 Japanese postmenopausal women revealed a significant association of the -381T/C variation of the BNP gene with radial BMD (r = 0.17, P = 0.01). Homozygous T-allele carriers had the lowest BMD values (0.395 +/- 0.056 g/cm(2)), homozygous C-allele carriers had the highest (0.429 +/- 0.051 g/cm(2)), and heterozygous individuals had intermediate radial BMD values (0.405 +/- 0.048 g/cm(2)), indicating a dosage effect. Accelerated bone loss also correlated with the -381 T allele in a 5-year follow-up study (r = 0.21, P = 0.017). These results suggest that variation of BNP may be an important determinant of postmenopausal osteoporosis, in part through the mechanism of accelerated postmenopausal bone loss.

Adult↗
PubMed2003

Association of a Trp16Ser variation in the gonadotropin releasing hormone signal peptide with bone mineral density, revealed by SNP-dependent PCR typing.

Osteoporosis is believed to result from interplay among multiple environmental and genetic determinants, including factors that regulate bone mineral density (BMD). Among those factors, adequate estrogen is essential for achievement of peak bone mass as well as for postmenopausal maintenance of skeletal homeostasis. Gonadotropin-releasing hormone (GnRH) from the hypothalamus is the primary determinant in the hypothalamic-pituitary-gonadal feedback system. In genetic studies of 384 postmenopausal Japanese women, we found a significant association between BMD and an amino acid variation (Trp16Ser) located within the signal peptide of GnRH (r = 0.143, P = 0.005). These results were achieved by genotyping all subjects using a newly developed SNP-dependent PCR method. This automated, high-throughput, and inexpensive procedure is suitable for typing large numbers of samples. BMD was lowest among 16Ser/Ser homozygotes, highest among 16Trp/Trp homozygotes, and intermediate among heterozygotes. A case-control study involving 125 osteoporosis patients and 92 healthy controls revealed a significant association between the presence of a 16Ser GnRH allele and affected status (chi(2) = 4.74, P = 0.041). The results suggested that variation of the GnRH signal peptide may be an important risk factor for postmenopausal osteoporosis.

Adult↗
PubMed2003

Association of a promoter haplotype (-1542G/-525C) in the tumor necrosis factor receptor associated factor-interacting protein gene with low bone mineral density in Japanese women.

Osteoporosis, a multifactorial common disease, is believed to result from the interplay of multiple environmental and genetic factors that regulate bone mineral density (BMD). Tumor necrosis factor receptor associated factor-interacting protein (I-TRAF) is an essential effecter of the tumor necrosis factor receptor-signaling cascade, one of the most potent bone-resorbing systems. In genetic studies of 382 Japanese adult women, we found that genotypes of two promoter variations of I-TRAF gene, -1542T/G and -525G/C, were similarly associated with radial BMD levels. Two variations were in almost complete linkage disequilibrium (D' = 0.978, r(2) = 0.917, chi(2) = 695, 2, P = 3.4 x 10(-153)), and there were two exclusive haplotypes (-1542T/-525C, frequency 0.74, and -1542G/-525G, frequency 0.24) among our test subjects. When BMD values were compared among the three haplotypic categories (-1542G/-525G homozygotes, heterozygotes, and -1542T/-525C homozygotes), BMD was lowest among -1542G/-525C homozygotes (mean +/- SD = 0.382 +/- 0.060 g/cm(2)), highest among -1542T/-525G homozygotes (0.405 +/- 0.051 g/cm(2)), and intermediate among heterozygotes (0.395 +/- 0.056 g/cm(2)) (r = 0.11, P = 0.030). The observed trend supported a codominant effect of the relevant haplotype of I-TRAF gene in determination of radial BMD. These results suggested that variation of I-TRAF might be an important determinant for postmenopausal osteoporosis.

Adaptor Proteins, Signal Transducing↗
PubMed2003

Association of a haplotype (196Phe/532Ser) in the interleukin-1-receptor-associated kinase (IRAK1) gene with low radial bone mineral density in two independent populations.

Osteoporosis, a multifactorial common disease, is believed to result from the interplay of multiple environmental and genetic determinants, including factors that regulate bone mineral density. Interleukin-1 (IL-1) is one of the most potent bone-resorbing factors, and interleukin-1-associated kinase 1 (IRAK1) is an essential effector of the IL-1 receptor signaling cascade. In genetic studies of two independent populations of postmenopausal women (cohort A: 220 individuals and cohort T: 126 individuals) from separated geographical regions of Japan, we found that radial bone mineral density levels had similar associations with IRAK1 genotypes in both populations. Two amino acid-substituting variations in the gene, encoding Phe196Ser and Ser532Leu, were in complete linkage disequilibrium (D' = 1.0000, r2 = 1.0000, chi2 = 192.000, p = 1.2 x 10(-43)), and we found two exclusive haplotypes (196F/532S, frequency 0.74; 196S/532L, frequency 0.26) of the IRAK1 gene among our test subjects. In both populations, a significant association with decreased radial bone mineral density was identified with haplotype 196F/532S (in cohort A: r = 0.21, p = 0.0017; in cohort T: r = 0.23, p = 0.011). Radial bone mineral density was lowest among 196F/532S homozygotes, highest among 196S/532L homozygotes, and intermediate among heterozygotes. Accelerated bone loss also correlated with the 196F/532S haplotype in a 5-year follow-up. These results suggest that variation of IRAK1 may be an important determinant of postmenopausal osteoporosis, in part through the mechanism of accelerated postmenopausal bone loss.

Base Sequence↗
PubMed2003

Association of molecular variants, haplotypes, and linkage disequilibrium within the human vitamin D-binding protein (DBP) gene with postmenopausal bone mineral density.

UNLABELLED: Possible contribution of vitamin D-binding protein (DBP) gene for determination of BMD was tested by characterizing 13 SNPs in 384 adult Japanese women. When the effect of a specific single SNP was tested, five SNPs (-39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) correlated with BMD significantly at various levels. The chromosomal dosage of one haplotype (T-C-C-G-T-C in -39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E, and IVS11+1097G>C) displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Multiple regression analyses revealed a most significant correlation with the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis. INTRODUCTION: Osteoporosis results from the interplay of multiple environmental and genetic determinants. The gene encoding vitamin D-binding protein (DBP), a key factor for regulating calcium homeostasis through the vitamin D endocrine system, is a probable candidate for conferring susceptibility to osteoporosis. METHODS: To test a possible contribution of the DBP gene for determination of bone mineral density (BMD) of adult women, we have characterized 13 single nucleotide polymorphisms (SNPs) within the DBP gene in DNA from 384 adult Japanese women and attempted to correlate specific SNPs with BMD. RESULTS AND CONCLUSIONS: Sixteen major haplotypes accounted for 80% of the variations, indicating allelic complexity in this genomic region. Pairwise linkage disequilibrium (LD), measured by the D' and r2 statistics, demonstrated a general pattern of decline with increasing distance, but individual LD values within small genomic segments were diverse. Regression analysis for adjusted BMD revealed significant correlation with respect to five of them (-39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, and IVS11+1097G>C) at various levels. An intronic SNP (IVS11+1097G>C) with the highest significance of association (p = 0.006) showed significant LD with four SNPs located around the first exon (r2 values > 0.18, D' > 0.5). A non-synonymous coding SNP, D432E, showed a comparable level of correlation, but it was in a moderate LD only with IVS11+1097G>C. The chromosomal dosage of one haplotype (T-C-C-G-T-C in -39C>T, IVS1+827C>T, IVS1+1916C>T, IVS1-1154A>G, D432E and IVS11+1097G>C) estimated in each subject displayed significant correlation with adjusted radial BMD (r = 0.15, p = 0.008; n = 331). Furthermore, multiple regression analyses revealed that the most significant correlation was achieved for the combination of IVS1+827C>T and D432E (r2 = 0.029, p = 0.005). These results indicate a complex combined effect of several SNPs within the DBP gene that might underlie susceptibility to low radial BMD and osteoporosis.

Aged↗
PubMed2003

[Role of physician on the treatment of osteoporosis].

Physicians play an important role on the chronic management of the elderly patients. Those patients usually have multiple disorders and these situations lead to us to determine the priority of the treatments because of socio-economical reason or tolerability of the patient against multiple drugs usage. Among the many involutional diseases, osteoporosis is considered to have less priority than the other diseases such as atherosclerosis, by physicians. However, fractures, most serious complication of osteoporosis, result in deteriorated ADL or QOL in osteoporotic patients. Therefore, when the elderly patients with osteoporosis are expected to have longevity or to have higher risks for future fracture, we should give a higher priority for the treatment of fracture prevention. Recent progress in the prevention of fractures allows us to treat osteoporosis with higher priority since the recently launched drug for osteoporosis such as bisphosphonates showed potent ability to reduce incident fractures.

Aged↗
PubMed2003

[Concurrent or sequential treatment for osteoporosis with PTH and alendronates].

PTH is a potent stimulator for both bone resorption and formation. The clinical application of PTH on osteoporosis resulted in marked increase in lumber BMD. However, the BMD in the cortical bone site was decreased by PTH administration. Furthermore, serious reduction of lumber BMD after cessation of PTH has been reported. To resolve these disadvantages of PTH treatment in osteoporosis, concurrent or sequential treatment of PTH and alendronate has been proposed. The results seemed to be promising because those modes of treatments showed significant increase in BMD at all bone sites and there was no withdraw phenomenon on BMDs after the cessation of PTH administration. Thus, the sequential or concurrent treatment of PTH and alendronate may be a powerful tool for the prevention of osteoporosis fracture.

English Abstract↗
PubMed2003

[Evidences and the taking measurements against G-I tract adverse events in amino bisphosphonate].

Amino bisphosphonate (A-BP) is a potent inhibitor of bone resorption through inhibition of mevalonate pathway resulting in increase apoptosis of osteoclast. It is expected that the same metabolic effects of this compound may contribute on the cell damage at G-I tract. Although the some endoscopical studies indicated that alendronate administration significantly associated gastric ulcer or erosion, the data were inconsistent between the studies. Furthermore, recent analysis revealed that A-BP did not increase in adverse events in G-I tract from the reviews of the mega-trials of alendronate and risedronate. Post-marketing surveillance also indicated that amino A-BP did not increase in G-I adverse event (AE) at G-I tract, but physicians have to pay attention about G-I AE after A-BP treatment in the individual patients.

English Abstract↗