Biomedical subjects

M Kanzawa

Publications and source records attributed to M Kanzawa.

12 recordsLinked to original sources

PubMed2002

The presence and severity of vertebral fractures is associated with the presence of esophageal hiatal hernia in postmenopausal women.

We examined the relationship between the presence of esophageal hiatal hernia (HH) assessed by endoscopy and the presence of vertebral fractures (VFs) in 87 Japanese postmenopausal women (age range 52-87 years). We found that 29 (63%) of 46 patients with HH (71.2+/-6.1 years, mean +/- SD) had one or more VFs, compared with 14 (34%) of 41 patients without HH (70.8+/-6.8 years), which was a significant difference in the frequency of VFs (c2 = 7.242; p = 0.0071). The average number of VFs per patient was significantly higher for the patients with HH than for those without HH (1.67+/-1.75 vs 0.68+/-1.21, p = 0.0032). There were no significant differences in absolute or age-matched bone mineral density (BMD) values at the lumbar spine (0.656+/-0.131 vs 0.662+/-0.148 g/cm2; Z-score, -0.35+/-1.17 vs -0.26+/-1.00) and there were no significant differences in biochemical parameters, age, years since menopause or body mass index (BMI) between the two groups. When patients were divided into those with reflux esophagitis (RE) (n = 30, 70.2+/-7.3 years) and those without RE (n = 57, 71.4+/-5.9 years), no significant differences were detected in any of the above parameters including the presence or number of VFs. The patients were further subdivided into four groups: those with 'HH only' (n = 23, 72.3+/-4.6 years), with 'RE only' (n = 7, 70.9+/-7.7 years), with 'both' (n = 23, 70.0+/-7.3 years) and with 'neither' (n = 34, 70.8+/-6.7 years). One or more VFs were found in 12 (52%), 1 (14%), 17 (74%), and 13 (38%) patients in each group, respectively, and the difference in frequency was significant (c2 = 10.748; p = 0.0132). The average number of VFs per patient in each group was 1.57+/-2.06, 0.14+/-0.38, 1.78+/-1.41 and 0.79+/-1.30, respectively, and there were significant differences between the 'both' and 'neither' groups, and between the 'both' and 'RE only' groups (p<0.05). When univariate logistic regression analysis was performed with the presence of HH as a dependent variable and each of the presence of VFs, the number of VFs per patient, absolute or age-matched BMD values at the lumbar spine, BMI and plasma albumin as independent variables, the presence of VFs and the number of VFs per patient were selected as indices affecting the presence of HH (odds ratio: 3.29 and 1.59, 95% confidence interval: 1.36-7.94 and 1.14-2.23; p=0.0080 and 0.0064, respectively). These results show that the presence and severity of VFs are associated with the presence of HH but not of RE in Japanese postmenopausal women, and suggest that kyphosis induced by multiple VFs might predispose elderly women to a complication with HH.

Aged↗

PubMed2001

Determinants of bone mineral density and spinal fracture risk in postmenopausal Japanese women.

The present study analyzed the factors that determine bone mineral density (BMD) and predict spinal fracture risk in postmenopausal Japanese women. Two hundred and five postmenopausal Japanese women aged 48-84 years (mean age 64 years) were enrolled in the cross-sectional study. BMD of the lumbar spine, femoral neck and total body as well as body composition were measured by dual-energy X-ray absorptiometry (DXA). Mid-radial BMD was measured by single-photon absorptiometry. We also determined serum levels of insulin-like growth factor (IGF)-I, IGF binding protein-2, -3 and osteocalcin as well as urinary levels of pyridinoline (Pyr), deoxy-Pyr (D-Pyr) and growth hormone. Multiple regression analysis revealed that lean body mass (LBM) was positively correlated with BMD at all sites. In contrast, femoral neck BMD was highly related to fat mass as well as LBM, although fat mass was not an independent correlate of total body and mid-radial BMD. LBM and urinary D-Pyr were crucial determinants at all sites except the mid-radius in stepwise regression analysis. Fat mass and serum IGF-I were determinants of femoral neck and mid-radial BMD, respectively. In terms of reproductive history, parity affected lumbar BMD. Factors affecting BMD differed according to the site. On the other hand, lumbar BMD as well as serum levels of IGF-I and albumin were selected as predictors of spinal fracture risk in multiple logistic regression analysis. Lumbar BMD, serum IGF-I and LBM were selected in women with lumbar BMD above 0.727 g/cm2. In conclusion, the present study indicates that LBM is a more important determinant of BMD than fat mass at any site except the femoral neck. Age, serum IGF-I and urinary D-Pyr were also determinants of BMD, dependent on the regions measured. Lumbar BMD and LBM as well as serum levels of IGF-I and albumin were useful markers which predicted the risk of osteoporotic spinal fractures in postmenopausal Japanese women.

Absorptiometry, Photon↗

PubMed2001

Association of polymorphic alleles of the calcium-sensing receptor gene with the clinical severity of primary hyperparathyroidism.

OBJECTIVE: Primary hyperparathyroidism (pHPT) is a heterogeneous disease in its clinical course and severity. Previous studies have suggested an association between the clinical severity of pHPT and the genotypes of vitamin D receptor, oestrogen receptors and PTH molecules. The Ca-sensing receptor (CaR) is activated by an extracellular calcium ion and controls PTH secretion, and thus polymorphisms of CaR might be associated with the magnitude of PTH secretion and the clinical severity of pHPT. In this study, we examined the relationship between CaR polymorphisms and biochemical markers in pHPT patients. METHODS: We analysed 105 Japanese pHPT patients (85 females and 20 males; mean age 55.6 +/- 14.0 years). We determined the CaR genotypes of G990R and intron 5 polymorphisms with genomic DNA extracted from peripheral lymphocytes. The intron 5 polymorphism was defined as T/T, T/C and C/C. RESULTS: In the G990R polymorphism, serum levels of both intact PTH and alkaline phosphatase (ALP) were significantly higher and the serum level of phosphorus was significantly lower in the RR group than in the GG group. In the intron 5 polymorphism, the T/T group showed significantly lower serum levels of intact PTH and Ca. Furthermore, patients with both the codon 990 RR and the intron 5 C allele (the RRC(+) group) had significantly higher serum levels of intact PTH and ALP than did the other patients. CONCLUSIONS: The present study is the first to show that CaR polymorphisms of G990R and intron 5 were closely associated with the magnitude of PTH secretion and/or PTH degradation as well as the clinical severity in pHPT patients.

Adolescent↗

PubMed2001

Plasma leptin concentrations are associated with bone mineral density and the presence of vertebral fractures in postmenopausal women.

OBJECTIVE: Although total fat body mass (FM) is considered to be one of the major determinants of bone mass, the mechanism by which FM and bone mass are positively correlated remains unclear. Leptin, the product of the obese (ob) gene, is secreted from adipocytes and its plasma levels are known to be positively correlated with %fat (FM divided by total body weight). There is recent evidence suggesting that leptin directly stimulates osteoblastic differentiation. Thus it is possible that the anabolic action of this hormone on bone may participate in the positive correlation between FM and bone mass. In this study, we analysed the relationships between either plasma leptin levels or %fat vs. bone mineral density (BMD) values as well as the presence of vertebral compression fractures, and evaluated whether or not plasma leptin levels were associated with BMD or bone fragility in a manner independent of FM. PATIENTS: One hundred and thirty-nine postmenopausal women (age 48-78 years, mean 62.5), who visited our outpatient clinic for the evaluation of osteoporosis. DESIGN AND MEASUREMENTS: Plasma concentrations of leptin after an overnight fast were measured by radioimmunoassay. BMD values were measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral neck and whole body. Distal one-third of radius BMD was measured by single photon absorptiometry (SPA). Vertebral fractures were assessed by lateral thoracic and lumbar spine radiographs. RESULTS: Although neither plasma leptin levels nor %fat correlated with age, there was a significant positive correlation between plasma leptin levels and %fat (r = 0.563, P < 0.001). Plasma leptin levels were significantly and positively correlated with BMD values at all skeleton sites measured, and multiple regression analysis revealed that this positive relationship was still observed with BMD values of the femoral neck and of the whole body, even after %fat and age were taken into account. Moreover, plasma leptin levels but not %fat were significantly lower in women with vertebral fractures than in those without fractures. When multiple logistic regression analysis was performed with either plasma leptin value or %fat employed as independent variables, plasma leptin values but not %fat were selected as an index affecting the presence of vertebral fractures. CONCLUSION: Our study showed that plasma leptin levels but not %fat are associated with BMD and the presence of vertebral fractures in postmenopausal women, suggesting that circulating leptin might play a physiological role in maintaining bone mass as well as better bone quality.

Adipose Tissue↗

PubMed2000

Association between parathyroid hormone (PTH)/PTH-related peptide receptor gene polymorphism and the extent of bone mass reduction in primary hyperparathyroidism.

Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analyzed the relationship between polymorphism of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor gene existing in exon M7 and the clinical characteristics of primary hyperparathyroidism (pHPT). PTH/PTHrP receptor genotypes were analyzed in 92 pHPT patients by direct sequence to determine whether nucleotide 1417 of the cDNA was C or T. BMD levels at the lumbar spine and at the radius before and one year after parathyroidectomy, as well as serum levels of calcium, phosphorus, alkaline phosphatase (ALP) and intact PTH were measured. Although there were no significant differences in serum levels of calcium, phosphorus and intact PTH, ALP was significantly lower in the CT genotype compared with the TT genotype. BMD level at the radius was significantly higher in the CT genotype than in the CC genotype. Moreover, an increase in radial BMD one year after parathyroidectomy was significantly less in CT genotype than two other genotypes (CC, TT). The present study is the first to indicate that the polymorphism of PTH/PTHrP receptor gene is closely related to the extent of bone mass reduction in pHPT and that this polymorphism would be one of the genetic factors responsible for the severity of the pathological state of pHPT.

Alkaline Phosphatase↗

PubMed2000

Association of polymorphic alleles of the calcium-sensing receptor gene with parathyroid hormone secretion in hemodialysis patients.

The present study was performed to investigate the association of calcium-sensing receptor (CaSR) genotypes with parathyroid hormone (PTH) secretion in hemodialysis patients. Subjects were 122 Japanese hemodialysis patients, including 39 patients with diabetes mellitus (DM). The CaSR polymorphisms tested were codon 990 in intracellular domain (A/A, A/G, and G/G groups) as well as T to C base change of intron 4 (T/T, T/C, and C/C groups). Statistical analysis of these polymorphisms revealed that the serum PTH level was significantly higher in the A/A group than in the G/G group in the former. In addition, the serum PTH level was also significantly higher in patients displaying C allele, as compared with the T/T group in the latter. This association of two polymorphisms with the serum PTH level was observed only in non-DM patients. Although two polymorphisms affected the PTH level independently, patients who possessed both genotypes (AAC+) had a markedly high level of PTH not only in the non-DM group but also in the DM group. The present findings indicate the possibility of the prediction for the extensive progression of secondary hyperparathyroidism through analyzing the CaSR polymorphisms in chronic hemodialysis patients.

Adult↗

PubMed2000

Involvement of osteoprotegerin/osteoclastogenesis inhibitory factor in the stimulation of osteoclast formation by parathyroid hormone in mouse bone cells.

OBJECTIVE: Recently, osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF) has been shown to inhibit osteoclast differentiation. On the other hand, we have reported that parathyroid hormone (PTH) stimulated osteoclast formation, presumably through a PTH-responsive cAMP-dependent protein kinase (PKA) pathway, in mouse bone cells. DESIGN AND METHODS: The present study was performed to examine how OPG/OCIF expression is regulated by PTH and to further investigate the possible involvement of OPG/OCIF in the stimulation of osteoclast formation by PTH in mouse bone cells. OPG/OCIF mRNA expression was analyzed by Northern hybridization after 24h treatments of mouse whole bone cells and mouse stromal cell line, ST2 cells with PTH or various second messenger analogs. RESULTS: Human (h) PTH(1-34) (10(-10) and 10(-8)mol/l) but not 10(-8)mol/l hPTH(3-34) down-regulated OPG/OCIF mRNA expression in mouse bone cells. Dibutyryl cAMP, but not phorbol ester, an activator of protein kinase C, or A23187, a calcium ionophore, down-regulated it. The same was also observed in ST2 cells, suggesting that stromal cells are responsible for the inhibitory effect of PTH and cAMP analogs on OPG/OCIF mRNA expression in mouse bone cells. CONCLUSIONS: The present study indicates that PTH down-regulates OPG/OCIF mRNA expression through the PKA pathway in stromal cells, which would result in the stimulation of osteoclast formation.

Animals↗

PubMed1999

High extracellular calcium inhibits osteoclast-like cell formation by directly acting on the calcium-sensing receptor existing in osteoclast precursor cells.

Although it has recently been suggested that high extracellular calcium ([Ca(2+)](e)) inhibits osteoclast function via a calcium-sensing receptor (CaSR) in mature osteoclasts, the role of CaSR in the regulation of osteoclast formation remains unknown. The present study was performed to investigate whether osteoclast precursor cells possess CaSR and to clarify the possible role of CaSR in the regulation of osteoclast formation. Immunocytochemistry detected CaSR in osteoclast precursor cells derived from spleen cells as well as in osteoblastic MC3T3-E1 cells. The use of reverse-transcription polymerase chain reaction (RT-PCR) with CaSR-specific primers, followed by nucleotide sequencing of the amplified products, also identified CaSR transcripts in osteoclast precursor cells derived from spleen cells as well as in MC3T3-E1 cells. High [Ca(2+)](e) (3 to 5 mM) concentration dependently inhibited 1,25(OH)2D3- or human parathyroid hormone (hPTH) (1-34)-induced osteoclast-like cell (Ocl) formation from osteoclast precursor cells derived from spleen cells. Further, the CaSR agonist neomycin also concentration dependently inhibited 1,25(OH)2D3- or hPTH(1-34)-induced Ocl formation. Moreover, a calcimimetic which mimics or potentiates the effects of [Ca(2+)](e) at the CaSR NPS R-467 (1-100 microM) concentration dependently inhibited Ocl formation stimulated by 1,25(OH)2D3 or hPTH(1-34). These findings first demonstrated that osteoclast precursor cells possess CaSR very similar, if not identical, to those in the parathyroid and kidney. Furthermore, the CaSR in osteoclast precursor cells could play a key role in regulating Ocl formation by sensing local changes in [Ca(2+)](e) at the resorptive sites.

Animals↗

PubMed1999

Parathyroid hormone gene polymorphisms in primary hyperparathyroidism.

OBJECTIVE: Genetic contributions to bone mineral density (BMD) and bone turnover are well known. In the present study, we analysed the relationship between restriction fragment length polymorphisms of the PTH gene and the development of primary hyperparathyroidism (pHPT) as well as its severity. PATIENTS: Seventy-nine pHPT patients and 104 age-matched healthy controls were analysed. DESIGN AND MEASUREMENTS: PTH genotypes were determined by polymerase chain reaction and BstB I or Dra II restriction fragment length polymorphisms. The presence and absence of BstB I or Dra II restriction sites of the PTH gene were indicated by B and b or D and d, respectively. BMD levels at the lumbar spine and at the radius were measured in all subjects. Serum levels of calcium, phosphorus, alkaline phosphatase and intact PTH were measured in pHPT patients. RESULTS: There were no differences in the frequencies of these PTH genotypes between pHPT patients and controls. In control subjects, lumbar BMD was significantly higher in BB genotype than in Bb/bb genotypes. In pHPT patients, there was no difference of BMD between BB and Bb/bb genotypes. In pHPT patients, serum calcium level was significantly higher in those with the BB genotype than Bb/bb genotypes. On the other hand, there was no association between Dra II polymorphism and BMD in both controls and pHPT patients, but serum intact PTH level was significantly higher in DD genotype than Dd/dd genotype in pHPT patients. Moreover, serum levels of ALP and intact PTH were significantly higher in the PTH BBDD haplotype, compared to those in haplotypes other than BBDD. CONCLUSIONS: The present study suggests that the BstB I polymorphism of PTH gene is closely related to bone mineral density and that PTH gene polymorphisms do not seem to affect the development of primary hyperparathyroidism but may relate to the severity of primary hyperparathyroidism.

Alkaline Phosphatase↗

PubMed1999

Effect of recombinant human growth hormone in elderly osteoporotic women.

OBJECTIVE: Bone mineral density and growth hormone (GH) secretion rate both decline during normal human ageing. We evaluated the effects of recombinant human GH on markers of body composition and bone turnover in an open study in 8 elderly osteoporotic women aged 68-75 years (mean age 71 years). DESIGN: Subjects were treated with GH as a single daily subcutaneous injection (0.125 IU/kg/week for the first 4 weeks and subsequently 0.25 IU/kg/week) for 48 weeks. RESULTS: GH treatment caused a rapid (within 2 weeks) increase in serum levels of IGF-I and IGF-binding protein-3 (IGFBP-3) which was sustained throughout the study. Markers of bone formation and resorption were both gradually increased up to 24 weeks of GH treatment. The bone formation markers, osteocalcin (OC) and bone alkaline phosphatase, remained high during GH treatment, while the bone resorption marker, deoxypyridinoline (D-Pyr), tended to return to baseline levels after 24 weeks of GH therapy. GH treatment for 48 weeks caused a significant increase in hand grip and a decrease in waist/hip ratio. The mean percentage changes in bone mineral density (BMD) of mid-radius and lumbar spine were + 2.1% and + 1.2%, respectively, although they were not statistically significant. GH treatment was well tolerated and no major side-effects except mild oedema and joint pain were found. Since GH treatment produced durable increases in bone formation markers, BMD continued to be monitored after discontinuation of GH treatment for another 48 weeks, during which significant increases in radial and lumbar BMD (8.1 +/- 2.1 and 3.8 +/- 1.4% above pre- treatment values, respectively) were recorded. CONCLUSION: These results indicate that GH attenuates the decrease in muscle strength and bone mass as well as the gain of abdominal fat with ageing in elderly women. The present data provide useful information about the application of GH treatment in elderly women.

Aged↗

PubMed1998

Identification of an enhancer sequence in 5'-flanking region of 1A exon of mouse liver/bone/kidney-type alkaline phosphatase gene.

The 5'-flanking region of the 1A exon of the mouse liver/bone/kidney-type alkaline phosphatase (L/B/K ALP) gene was analyzed for the promoter activity. Luciferase assays revealed that a segment containing a 9 bp inverted repeat (nt -1212 to -1179, designated as IRS for inverted repeat segment) had an enhancer activity. Though an E-box at nt -234 did not have a prominent promoter activity, the effect of IRS required its presence. Both transcriptional activity and IRS binding to the nuclear proteins were similarly observed even in cells that did not express ALP. Bone morphogenetic protein-2 (BMP-2) induced the ALP expression in pluripotent C3H10T1/2 cells, but it did not increase the transcriptional activity of the promoter region. Though they do not determine cell specific or BMP-2 inducible ALP expression, IRS and the E-box at position -241 seem to be important for the basic transcriptional activity of ALP gene.

3T3 Cells↗

PubMed1998

Age-dependent changes in body composition in postmenopausal Japanese women: relationship to growth hormone secretion as well as serum levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3.

The present study was performed to investigate the age-dependent changes in body composition and the possible role of growth hormone (GH), insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) in these changes in postmenopausal Japanese women. A total of 161 Japanese women aged 45-88 years (mean 62) were enrolled in the cross-sectional study. Body composition (bone mineral content (BMC), lean body mass (LBM) and fat) was measured by dual-energy X-ray absorptiometry, and the percentage of BMC, LBM and fat was calculated by dividing each absolute value of body composition by total body mass. Urinary GH concentration divided by creatinine in nocturnal urine samples collected just after waking was used as an index of endogenous GH secretion. Serum levels of IGF-I and IGFBP-3 were measured by RIA. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 declined with age. BMC, %BMC and LBM also declined with age, while fat mass and %fat did not obviously change with age. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 correlated positively with BMC, even if age was taken into account. On the other hand, urinary GH correlated negatively with fat and %fat. In contrast, serum levels of IGF-I and IGFBP-3 correlated positively with fat and %fat. LBM did not correlate with either urinary GH or serum IGFBP-3 levels but exhibited a weakly positive correlation with serum IGF-I level. The present study suggests that the GH-IGF-I-IGFBP-3 axis positively regulates bone mass, and that GH and IGF-I-IGFBP-3 inversely regulate fat mass, i.e. GH negatively and IGF-I-IGFBP-3 positively regulates it.

Aged↗