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1.
Z. Efstathiadou V. Kranas J. P. A. Ioannidis I. Georgiou A. Tsatsoulis 《Osteoporosis international》2001,12(4):326-331
Several genetic polymorphisms are implicated as determinants of bone mineral density (BMD) in postmenopausal women. These
include the Sp1 polymorphism of the collagen type Iα 1 (COLIA1) gene, the FokI and BsmI polymorphisms of the vitamin D receptor (VDR) gene, and the PvuII and XbaI polymorphisms of the estrogen receptor (ER) gene. The relative importance and the independence of these genetic effects
have not been studied simultaneously in the same population. We evaluated the effects of these polymorphisms on lumbar spine
BMD among 154 postmenopausal Greek women. BMD tended to differ across Sp1 genotypes (mean 0.842 g/cm2 in SS, 0.851 g/cm2 in Ss, 0.763 in ss, age-adjusted p = 0.056), mostly because ss homozygotes had lower BMD (p = 0.018 compared with SS and Ss). No other polymorphisms were associated with BMD in this population (p= 0.53 for FokI, p= 0.94 for BsmI, p = 0.80 for PvuII, p = 0.91 for XbaI). In multivariate modeling, the effect of ss homozygosity was clinically and statistically significant (–0.105 g/cm2, p= 0.013) after adjusting for age, weight, height, hormone replacement use, and the other four polymorphisms. None of the other
four polymorphisms was retained as an independent predictor of BMD in a backward elimination model and no significant synergistic
effects were observed when gene interactions were tested. When all five polymorphisms are considered simultaneously, the Sp1
COLIA1 polymorphism seems to have the most unequivocal effect on BMD, at least in postmenopausal women.
Received: 3 July 2000 / Accepted: 14 November 2000 相似文献
2.
Vitamin D Receptor Gene Polymorphisms and Bone Mineral Density in Elderly Chinese Men and Women in Hong Kong 总被引:8,自引:0,他引:8
E. M. C. Lau R. P. Young S. C. H. Ho J. Woo J. L. Y. Kwok Z. Birjandi G. N. Thomas A. Sham J. A. J. H. Critchley 《Osteoporosis international》1999,10(3):226-230
Although genetic factors have been strongly implicated in determining bone mineral density (BMD), the role of the vitamin
D receptor (VDR) polymorphism remains controversial. An overall consensus is difficult, as the populations studied have been
heterogeneous with respect to menopausal status and ethnicity. Moreover, some studies have examined only small populations,
and relatively few studies have been conducted in Asian populations. There is mounting evidence that calcium homeostasis in
Asian populations differs from that in Caucasians. This difference may be mediated, in part, through VDR effects. In a cross-sectional
study we have examined the relationship between the VDR polymorphism and BMD in 272 women (mean age 75 years) and 237 men
(mean age 73 years) of Chinese origin from Hong Kong. Consistent with other studies in Asian populations we found higher frequencies
of the T, b and a alleles compared with those reported in Caucasian populations. Moreover, no significant difference in BMD
was observed when subjects were grouped by a combination of the genotypes (bbAATT, bbAaTT, bbaaTT, BbAaTt, BbAATt). These
results suggest that VDR polymorphism is not associated with BMD in elderly Hong Kong Chinese men and women.
Received: 16 July 1998 / Accepted: 15 February 1999 相似文献
3.
H.-Y. ChenChen W.-C. Chen W.-C. Chen F.-J. Tsai C.-H. Tsai C.-W. Li 《Osteoporosis international》2001,12(12):1036-1041
Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of the vitamin
D receptor gene intron 8 BsmI polymorphism with bone mineral density (BMD) and their relationship to osteoporosis. We determined the vitamin D receptor
gene intron 8 BsmI polymorphism using polymerase chain reaction-based restriction analysis in 171 postmenopausal Chinese women in Taiwan. The
polymorphism was detected using the restriction enzyme BsmI, where the B allele indicated absence of the cuttable site and the b allele its presence. BMD of the lumbar spine and proximal
femur were measured using dual-energy X-ray absorptiometry. The allelic frequencies for postmenopausal Chinese women in Taiwan
were 12.3% for B and 87.7% for b in BsmI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was: 6.4% BB, 11.7% Bb
and 81.9% bb. The three genotypic groups differed significantly in BMD at the lumbar spine and the femoral neck. These differences
corresponded to significant gene-dose effects at the lumbar spine and femoral neck (p<0.001 for both sites). The relative risk for the development of osteoporosis was about 2–3 times as great as that predicted
by the differences between genotypes in BMD, and remained significant even after adjustment for age, height and weight. The
vitamin D receptor gene intron 8 BsmI polymorphism is associated with reduced BMD and predisposes women to osteoporosis.
Received: 21 February 2001 / Accepted: 31 May 2001 相似文献
4.
Y. V. Ho E. M. Briganti Y. Duan R. Buchanan S. Hall E. Seeman 《Osteoporosis international》1999,9(2):134-138
Corticosteroid therapy (CST) is associated with reduced intestinal calcium absorption, bone loss and increased fracture risk.
As polymorphisms of the vitamin D receptor (VDR) gene may be associated with bone mineral density (BMD) and intestinal calcium
absorption, we asked whether patients with a given VDR genotype receiving CST may be at increased or decreased risk for corticosteroid-related
bone loss and osteoporosis. We measured areal BMD (g/cm2) by dual-energy X-ray absorptiometry in 193 women (50 premenopausal, 143 postmenopausal) and 70 men with rheumatoid arthritis
(n= 44), obstructive airway diseases (n= 128) and other corticosteroid-treated diseases (n= 91). All patients received a cumulative dose greater than 1.8 g per year or a minimum of 5 mg daily of prednisolone or equivalent
for at least 1 year. VDR alleles were typed by polymerase chain reaction assay based on the polymorphic BsmI and TaqI restriction sites. BMD in patients was expressed as a Z-score (mean ± SEM) derived from age- and gender-matched controls. BMD was reduced in patients at the lumbar spine (bb, −0.52
± 0.12; Bb, −0.47 ± 0.11; BB, −0.65 ± 0.18 SD; p<0.01), femoral neck (bb, −0.46 ± 0.10; Bb, −0.34 ± 0.10; BB, −0.54 ± 0.14 SD; p<0.01), Ward’s triangle (bb, −0.44 ± 0.10; Bb, −0.31 ± 0.10; BB, −0.45 ± 0.13 SD; p<0.01), and trochanter (bb, −0.50 ± 0.10; Bb, −0.30 ± 0.10; BB, −0.44 ± 0.14 SD; p<0.01). However, there was no significant difference in the deficit in BMD in any of the genotypes, either before or after
adjusting for age, sex, body mass index, disease type, age at onset of disease, disease duration, cumulative steroid dosage,
smoking status and dietary calcium intake. Similarly, there were no detectable differences between the BsmI genotypes and the rate of bone loss in 79 patients with repeated BMD measurements at an interval of 4–48 months. The data
suggest that the VDR genotypes may not be a means of identifying patients at greater risk of corticosteroid-related bone loss.
Received: 23 December 1997 / Accepted: 26 May 1998 相似文献
5.
The Association of Bone Mineral Density with Vitamin D Receptor Gene Polymorphisms 总被引:16,自引:0,他引:16
G. Gong H. S. Stern S.-C. Cheng N. Fong J. Mordeson H.-W. Deng R. R. Recker 《Osteoporosis international》1999,9(1):55-64
A recent meta-analysis of 16 publications suggested that bone mineral density (BMD) is not associated with vitamin D receptor
(VDR) gene polymorphism (VDRGP) at the 0.05 significance level when a study with genotyping mistakes is excluded. We wished
to determine whether ‘positive’ findings supporting the BMD–VDRGP association may be explained by chance, and what factors
affect the outcomes of these studies. Seventy-five articles and abstracts on the association of VDRGP with BMD and related
skeletal phenotypes published before January 1997 were identified. Twenty-three of 67 (34.3%) studies on spinal BMD and 22
of 51 (43.1%) on femoral neck BMD had found a BMD–VDRGP association at p<0.05, significantly (p= 7 × 10–14 for spinal BMD, p= 9 × 10–16 for hip BMD) higher than the expected 5% false positive rate under the null hypothesis of ‘no association’. ‘Positive’ results
were more frequently observed in studies on females before the menopause than those on females after the menopause (p<0.02) or on male and female subjects combined (p<0.05) when skeletal phenotypes at any bone sites were considered. The ‘positive rate’ among studies was also influenced by
the age range of subjects studied and by the inclusion of subjects with osteoporosis. It is concluded that: (1) BMD is associated
with VDRGP with high levels of confidence and (2) non-genetic factors and genetic heterogeneity interfere with the detection
of the effects of VDRGP on bone phenotypes.
Received: 20 January 1998 / Accepted: 7 April 1998 相似文献
6.
R. W. Keen P. Egger C. Fall P. J. Major J. S. Lanchbury T. D. Spector C. Cooper 《Calcified tissue international》1997,60(3):233-235
Family and twin studies have demonstrated a strong genetic component to the development of peak bone mass. Early fetal and
infant environment has also been shown to influence bone mass through an effect on skeletal size and mineral content. We report
a retrospective study that has examined whether early infant growth is regulated by genetic factors shown to be associated
with bone mass. We have determined the vitamin D receptor (VDR) gene alleles for 66 women (mean age 65.5 years) on whom detailed
birth records were available. There was a statistically significant trend (P= 0.04) for VDR genotype against weight at the age of 1 year, with the ``tt' homozygote group having 7% higher weight. We
conclude that early fetal or infant environment may interact with an individual's underlying genotype to program early skeletal
growth, and that this may track through later life to influence adult characteristics. Further prospective studies are required,
however, to fully clarify the precise environmental and genetic mechanisms underlying these findings.
Received: 5 June 1996 / Accepted: 21 August 1996 相似文献
7.
R. Kikuchi T. Uemura I. Gorai S. Ohno H. Minaguchi 《Calcified tissue international》1999,64(2):102-106
To determine whether vitamin D receptor (VDR) gene polymorphisms are associated with bone mineral density (BMD) and bone
loss in the Japanese population, VDR BsmI RFLPs were analyzed in 191 postmenopausal Japanese women by comparing B allele and b allele DNA sequences, and a point mutation
was confirmed. We examined VDR BsmI restriction fragment length polymorphism (RFLP) with an amplification refractory mutation system (ARMS) using this point
of mutation. The frequency of VDR BsmI alleles in the Japanese population was significantly different from that in whites. The bb genotype was identified in 79.6%,
of the subjects, the Bb genotype in 19.3%, and the BB genotype was in only 1.1%. We find no significant differences in lumbar
spine baseline BMD between the bb genotype and the Bb genotype. In both early and late postmenopausal periods, serial measurements
of vertebral BMD revealed that subjects with the Bb genotype lost BMD faster than those with the bb genotype (P= 0.001). We conclude that there is a significant relationship between RFLPs of BsmI VDR and the annual rates of bone loss during early and late postmenopausal periods in the Japanese population.
Received: 14 May 1997 / Accepted: 9 July 1998 相似文献
8.
Holmberg-Marttila D Sievänen H Järvinen TL Järvinen TA 《Calcified tissue international》2000,66(3):184-189
BsmI restriction fragment length polymorphism (RFLP) of the vitamin D receptor (VDR) gene and PvuII RFLPs of the estrogen receptor (ER) gene and their relation to changes in areal bone mineral density (BMD) were examined
in 43 healthy postpartum Finnish women aged 31.3 (SD 4.7) years. BMD was measured by dual energy X-ray absorptiometry at lumbar
spine, right femoral neck, and dominant distal radius immediately after delivery, 1 month after resumption of menses, and
1 year thereafter. The RFLPs were represented as Bb (BsmI) and Pp (PvuII), the capital letters denoting the absence of and the small letters the presence of the restriction sites. The frequency
of VDR alleles was as follows: bb (20.9%), Bb (60.5%), and BB (18.6%), and that of ER alleles was pp (39.5%), Pp (51.2%),
and PP (9.3%). Altogether, BMD decreased significantly during postpartum amenorrhea at all sites [the mean bone loss ranging
from −1.2 (SD 3.6)% at the distal radius to −3.7 (2.9)% at the femoral neck], and increased after resumption of menses [the
1-year follow-up BMD values ranging from −1.0 (2.4)% at the femoral neck to +3.3 (4.0)% at the lumbar spine as compared with
baseline]. No obvious genotype-related differences were found between these changes. These results suggest that the BsmI and PvuII polymorphisms may not have substantial influence on BMD changes postpartum.
Received: 20 November 1998 / Accepted: 30 September 1999 相似文献
9.
Association Between Colles’ Fracture and Low Bone Mass: Age-Based Differences in Postmenopausal Women 总被引:3,自引:0,他引:3
E. Kanterewicz E. Kanterewicz A. Yañez A. Pérez-Pons I. Codony L. Del Rio A. Díez-Pérez 《Osteoporosis international》2002,13(10):824-828
Colles’ fracture (CF) in postmenopausal women has been linked to low bone mass at the lumbar spine and hip. However, the
diverse methodological approaches of previous studies make the results difficult to compare and thus the implications of CF
in osteoporosis daily clinical practice are not clear. We explored the association between CF and low bone mineral density
(BMD) in an incident case-control study in 58 postmenopausal Spanish women aged 45–80 years with recent CF and in 83 population-based
controls of the same age range. The BMD of ultradistal distal forearm, lumbar spine and hip was measured by dual-energy X-ray
absorptiometry (DXA) and WHO criteria were used to define osteoporosis and osteopenia. BMD was significantly lower in cases
for all three areas (p<0.001). Osteoporosis was more prevalent in cases than controls in the wrist (60% vs. 35%, p<0.001), lumbar spine (47% vs. 20%, p<0.005) and hip (19% vs. 6%, p<0.005). After adjusting for age, menopausal status and body mass index, osteoporosis and osteopenia remained significantly
associated with CF only in women aged 65 years or less (ultradistal forearm OR 5.7 (95% CI 1.2–27.2), lumbar spine OR 3.9
(95% CI 1.1–14.3)). We conclude that CF in postmenopausal women aged 65 or less may be used as a sentinel finding to identify
patients with generalized osteoporosis. Additionally, 70% of all CF patients regardless of their age had low bone mass (T-score<−1SD) in any studied site.
Received: 3 December 2001 / Accepted: 22 May 2002 相似文献
10.
Vitamin D Receptor Start Codon Polymorphism (Fok I) and Bone Mineral Density in Chinese Men and Women 总被引:4,自引:0,他引:4
The relationship between Fok I polymorphism of the vitamin D receptor start codon, bone mineral density (BMD) and vertebral
fractures was studied in 684 Chinese men and women. A significant trend was observed only in Chinese women aged 70–79 years.
The mean BMD at the total body was 0.85 ± 0.01 g/cm2, 0.82 ± 0.01 g/cm2and 0.84 ± 0.01 g/cm2 for elderly women of the FF, Ff and ff genotypes respectively (p= 0.06 by ANOVA). Similar but statistically non-significant trends were observed at the hip and spine. However, no association
between BMD and the Fok I genotype was observed in younger women (aged 50–59 years) and elderly men (aged 70–79 years). In
all study groups, there was no effect of an interaction between Fok I polymorphism and calcium intake on BMD (p>0.05 for the interaction effects by two-way ANOVA). No significant association was observed between Fok I polymorphism and
vertebral fracture in elderly men or women (p>0.05 by the chi-square test). We conclude that the Fok I polymorphism may have a weak effect on the BMD of elderly Chinese
women.
Received: 2 February 2001 / Accepted: 27 August 2001 相似文献
11.
Prevention of Bone Loss by Clodronate in Early Postmenopausal Women with Vertebral Osteopenia: A Dose-Finding Study 总被引:1,自引:0,他引:1
M. J. V?lim?ki K. Laitinen K. Laitinen A. Patronen H. Puolijoki H. Puolijoki J. Sepp?nen L. Pylkk?nenand the Probone Study Group 《Osteoporosis international》2002,13(12):937-947
This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the
prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53
years were recruited for the study. They were 1–5 years postmenopausal and their lumbar spine bone mineral density (BMD) was
at least 1 standard deviation below the mean of premenopausal women (T-score ≤−1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800
mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days
for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of
2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg
of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening,
and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were
−3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to
4.9%, p<0.0001)], and in the trochanter area BMD −1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference
between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5%
in the clodronate group and −0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between
groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral
neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% (p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% (p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% (p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% (p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between
clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate
in the extension phase. Clodronate in daily doses of 400–800 mg caused a slight elevation of aminotransferase levels, usually
within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose
of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively
reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective,
placebo-controlled trials.
Received: 4 March 2002 / Accepted: 9 July 2002 相似文献
12.
The Vitamin D Receptor Start Codon Polymorphism (Fok1) and Bone Mineral Density in Premenopausal Women in Taiwan 总被引:1,自引:0,他引:1
The vitamin D receptor gene (VDRG) polymorphism as a factor of bone turnover rate or bone mineral density (BMD) is a controversial
issue, especially in different ethnic populations. In addition to intron 8 (Bsm1, Taq1) and exon 9 (Apa1), VDRG polymorphism is present at its translation initiation site on exon 2. The VDRG has two translation initiation sites.
The first shows a thymine/cytosine polymorphism and can be detected by restriction fragment length polymorphism (RFLP) using
the endonuclease Fok1. This start codon polymorphism (SCP) of the VDRG was detected by polymerase chain reaction and then by RFLP with Fok1. While the f allele was assigned for the presence of the restriction site, the F allele was assigned for the absence of
the restriction site, and the encoded vitamin D receptor is shorter by three amino acids. We examined the association between
this SCP of the VDRG and bone turnover as well as BMD in 101 premenopausal Taiwanese women aged 40–53 years. Total body bone
mineral content and BMD of proximal femur and lumbar spine were measured by dual-energy X-ray absorptiometry. We found a prevalence
of 39.6% for the f allele of the VDRG. The frequencies of FF, Ff and ff genotypes were 35.6%, 49.5% and 14.9%, respectively.
There was no statistically significant difference in BMD at any site or bone turnover markers among the three Fok1 genotypes (FF, Ff and ff). The SCP is independent of Bsm1, Apa1 or Taq1 polymorphisms of the VDRG at intron 8 and exon 9. In conclusion, the SCP polymorphism detected by endonuclease Fok1 does not significantly influence BMD or bone turnover in premenopausal women in Taiwan.
Received: 7 July 1998 / Accepted: 10 November 1998 相似文献
13.
The Contribution of Vitamin D Receptor Gene Polymorphisms in Osteoporosis and Familial Osteoporosis 总被引:5,自引:0,他引:5
L. Fountas P. Moutsatsou I. Kastanias N. Tamouridis M. Tzanela M. Anapliotou C. E. Sekeris 《Osteoporosis international》1999,10(5):392-398
It is well established that genetic factors play a major role in the pathogenesis of osteoporosis. Previous reports have
suggested that vitamin D receptor (VDR) gene polymorphisms, particularly the BB, tt and AA genotypes, are associated with
low bone mineral density (BMD). If these VDR genotypes are indeed an important determinant of BMD, then a population of related
osteoporotic individuals (mother–daughter or sister–sister relationship) should have a high prevalence of the BB, tt or AA
VDR genotypes. To test this hypothesis we determined the VDR genotypes in 26 osteoporotic persons (age 44.3 ± 12.7 years,
mean ± SD) belonging to 12 families. Furthermore, for comparison with existing studies, we applied the VDR genotype analysis
in a population of 53 unrelated healthy subjects (age 45.2 ± 9.8 years, mean ± SD) and 59 unrelated osteoporotic subjects
(age 52.1 ± 9.0 years, mean ± SD). The menopausal status of the healthy and osteoporotic populations was pre-, peri- and mostly
early postmenopausal. The proportions of the three genotypes, BB, tt and AA, within the 12 osteoporotic families were 15%,
12% and 27%, respectively, whereas the proportions of the other three homozygous genotypes (bb, TT, aa) were 50%, 50% and
23%. The distribution of the BB, tt and AA genotypes in the normal population was 21%, 21% and 36%, respectively (vs bb, TT,
aa: 36%, 38%, 21%), whereas in the osteoporotic population it was 24%, 20% and 34% (vs bb, TT, aa: 27%, 34%, 14%). Our data
indicate that there is not a statistically significant (p>0.05) difference in the VDR genotype frequencies within osteoporotic families as compared with the same genotypes in the
population of unrelated normal or osteoporotic subjects. VDR genotype analysis showed no significant relation between VDR
polymorphisms and BMD or Z-score values at the lumbar spine. This study demonstrates the lack of a heritability pattern between the BB, tt and AA genotypes
and low BMD.
Received: 29 October 1998 / Accepted: 19 April 1999 相似文献
14.
Calcium and Vitamin D Supplementation Increases Spinal BMD in Healthy, Postmenopausal Women 总被引:2,自引:0,他引:2
We undertook a double-masked, randomized, placebo-controlled trial to evaluate the effect of a calcium and vitamin D supplement
and a calcium supplement plus multivitamins on bone loss at the hip, spine and forearm. The study was performed in 240 healthy
women, 58–67 years of age. Duration of treatment was 2 years. Bone mineral density (BMD) was measured at the lumbar spine,
hip and forearm. A dietary questionnaire was administered twice during the study and revealed a fairly good calcium and vitamin
D intake (919 mg calcium/day; 3.8 mg vitamin D/day). An increase in lumbar spine BMD of 1.6% was observed in the treatment
group after 2 years (p50.002). In the placebo group no significant changes were observed during the 2 years. Lumbar spine BMD was significantly
higher in the treatment group at both 1 (p50.01) and 2 years (p50.05) compared with the placebo group. Though not significant, the same trend was seen at the hip. No significant changes
from baseline values were observed at the distal forearm in either the treatment or the placebo group. In conclusion, we found
a significant increase in urinary calcium excretion in the treatment group compared with the placebo group. Together with
significant changes in serum calcium and serum parathyroid hormone, this indicates that a long-term calcium and vitamin supplement
of 1 g elementary calcium (calcium carbonate) and 14 mg vitamin D3 increases intestinal calcium absorption. A positive effect on BMD was demonstrated, even in a group of early postmenopausal
age, with a fairly good initial calcium and vitamin D status.
Received: 2 July 1997 / Accepted: 28 October 1997 相似文献
15.
O. M. Hauache M. Lazaretti-Castro S. Andreoni S. G. A. Gimeno C. Brandão A. C. Ramalho T. S. Kasamatsu I. Kunii L. F. Hayashi S. A. Dib J. G. H. Vieira 《Osteoporosis international》1998,8(3):204-210
Patients with insulin-dependent diabetes mellitus (IDDM) are at higher risk of developing osteoporosis. Among the genetic
factors related to the development of osteoporosis, a possible association between vitamin D receptor (VDR) gene polymorphism
and bone mineral density (BMD) has been described in some populations. We characterized the VDR gene polymorphism in a healthy
adult Brazilian population and in a group of patients with IDDM and correlated these findings with densitometric values in
both groups. The Brazilian population is characterized by an important racial heterogeneity and therefore is considered an
ethnically heterogeneous population. We recruited 94 healthy adult Brazilian volunteers (63 women and 31 men), mean (+ SD)
age 32.4 + 6.5 years (range 18–49 years), and 78 patients with IDDM (33 women and 45 men) diagnosed before 18 years of age,
mean (+ SD) age 23.3 + 5.5 years (range 18–39 years). VDR genotype was assessed by polymerase chain reaction amplification
followed by BsmI digestion on DNA isolated from peripheral blood leukocytes. Statistical analysis included Bonferroni t-test to compare densitometric values within different genotypes in both groups and multiple regression analysis of bone density
adjusted for potential confounding factors. The IDDM group had a lower BMD compared with the control group. The VDR genotype
distribution in the control group was 43 Bb (45.7%), 39 bb (41.5%) and 12 BB (12.8%). This distribution did not differ from that observed in the IDDM group: 39 Bb (50%), 26 bb (33.3%) and 13 BB (16.7%). In the IDDM group, patients with the Bb genotype had a higher body weight when compared with the BB genotype (p= 0.02). However, when diabetic patients were controlled for age, sex and body mass index, BB genotype was associated with a lower mean BMD at lumbar spine and femoral neck than in Bb and bb patients. BB patients had a shorter duration of IDDM than bb and Bb patients. These findings suggest a small influence of VDR gene polymorphism on BMD of a racially heterogeneous population
with IDDM.
Received: 5 March 1997 / Accepted: 23 September 1997 相似文献
16.
J. M. Zmuda J. A. Cauley M. E. Danielson T. M. Theobald R. E. Ferrell 《Osteoporosis international》1999,9(3):214-219
A polymorphism at the first of two potential translation initiation codons in the vitamin D receptor (VDR) gene defined by
the FokI restriction endonuclease has been associated with reduced bone mineral density (BMD) among Caucasian, Asian, and Mexican-American
women. We tested the hypothesis that the FokI polymorphism is related to markers of osteoporotic risk in 104 community-dwelling African-American women aged 65 years and
older. Six percent of the African-American women had the ff genotype, 32% were heterozygous, and 63% had the FF genotype.
FokI genotype frequencies did not differ from Hardy–Weinberg expectations. Hip and calcaneal BMD, calcaneal ultrasound attenuation
and hip geometry from pelvic radiographs did not differ significantly by FokI genotypes or between women with and without the rare FokI allele. There was also no association between the FokI polymorphism and biochemical markers of bone turnover or fractional calcium absorption. We conclude that the VDR start codon polymorphism does not have a major influence on osteoporotic risk in older African-American women.
Received: 20 November 1997 / Accepted: 29 June 1998 相似文献
17.
P. Aguado M. T. del Campo M. V. Garcés M. L. González-Casaús M. Bernad J. Gijón-Baños E. Martín Mola A. Torrijos M. E. Martínez 《Osteoporosis international》2000,11(9):739-744
To evaluate a possible relationship between vitamin D levels and bone mineral density (BMD) and the prevalence of hypovitaminosis
in a population of postmenopausal women from a rheumatologic outpatient clinic in Madrid, Spain, 171 postmenopausal women
(aged 47–66 years) divided into two groups (osteoporotic and nonosteoporotic, according to WHO criteria) were studied between
November and June. Liver and kidney function were normal in all subjects. Serum parathyroid hormone (PTH) and calcidiol levels
were determined and bone densitometry carried out at the lumbar spine and hip level. PTH and calcidiol serum levels did not
show any correlation. Serum PTH was inversely related to BMD at both hip and lumbar spine in the total group, and at the hip
with calcidiol levels lower than 37 nmol/l. Calcidiol was directly related to hip BMD only when levels were lower than 37
nmol/l. Results of a stepwise multiple regression analysis showed that the single factor which affected BMD at the hip was
calcidiol in the subgroup with serum calcidiol levels below 37 nmol/l, while in the subgroup with serum calcidiol levels above
37 nmol/l, the main factor affecting hip BMD was serum PTH. The prevalence of vitamin D deficiency at a cutoff of 37 nmol/l
was 64%. In summary, calcidiol serum levels below 37 nmol/l seem to affect bone mass, regardless of the effect of PTH. Vitamin
D deficiency is a frequent finding in the postmenopausal women who attend a rheumatology outpatient clinic in Madrid. Vitamin
D supplementation should therefore be considered in this population during the winter season.
Received: 2 July 1999 / Accepted: 3 March 2000 相似文献
18.
Hong-Wen Deng Jian Li Jin-Long Li M. Johnson G. Gong R. R. Recker 《Osteoporosis international》1999,9(6):499-507
Much work has been done on the association between vitamin D receptor (VDR) genotypes and bone mineral density (BMD). Despite
considerable effort, the results are inconsistent. While the VDR association remains unresolved, studies have expanded to
other candidate genes (i.e., estrogen receptor (ER) genotypes), also yielding inconsistent results. A few studies have suggested
that interaction effects between VDR and ER genotypes significantly affect BMD. We assessed associations of BMD with VDR BsmI genotypes, and ER XbaI and PvuII polymorphisms (denoted as ERX and ERP respectively) with spine, femoral neck, distal radius BMD, and with total body bone
mineral content (tbBMC) in 108 US Mid-western postmenopausal Caucasian women. We statistically controlled for confounding
factors such as height, weight, etc., in the analysis. No significant association was detected for ER genotypes with spine
and radius BMD, or for VDR genotypes with femoral neck and radius BMD and tbBMC. No significant interaction between VDR and
ER genotypes was detected in our sample. However, the VDR genotypes are significantly (p = 0.004) associated with *5.8% spine BMD variation. Both ERX and ERP genotypes are significantly (p = 0.02) associated with *3.5% femoral neck BMD variation. ERX genotypes are significantly (p = 0.03) associated with *2.4% tbBMC variation. However, if the data were analyzed by simple ANOVA as in some previous studies,
without adjusting statistically for confounding factors, all the significant results we found here would have gone undetected.
Our findings suggest that: (1) VDR and ER genotypes may have different effects on BMD at different sites and on tbBMC; and
(2) if significant factors influencing bone are not appropriately controlled, true significant associations can easily be
missed. These findings may offer a partial explanation for some of the earlier inconsistent results of association studies
on BMD with VDR and ER genotypes.
Received: 4 August 1998 / Accepted: 2 November 1998 相似文献
19.
Common Polymorphism of the Vitamin D Receptor Gene is Associated with Variation of Peak Bone Mass in Young Finns 总被引:10,自引:0,他引:10
A.-M. Viitanen M. Kärkkäinen K. Laitinen C. Lamberg-Allardt K. Kainulainen L. Räsänen J. Viikari M. J. Välimäki K. Kontula 《Calcified tissue international》1996,59(4):231-234
Previous studies suggested a relation between polymorphism of the vitamin D receptor (VDR) gene and bone mineral density
(BMD) at perimenopausal age. To enlighten the possible association of the VDR gene polymorphism and BMD, we studied young
(20–29 years) adults whose BMD provides a measure of their maximal bone mass. After sequencing the DNA regions flanking the
polymorphic BsmI site, we set up a specific solid-phase minisequencing technique to assay this allelic variation. BMD values
were adjusted for age, sex, weight, physical activity, smoking, and calcium intake. Young subjects homozygous for the b allele
(BsmI site present) had a significantly higher BMD in lumbar spine and femoral neck than those homozygous for the B allele
(BsmI site absent). This data shows that the BsmI polymorphism of the VDR gene is associated with peak bone mass. The implication
of this result regarding the prevention of osteoporosis deserves further attention.
Received: 3 July 1995 / Accepted: 13 February 1996 相似文献
20.
Bone Mineral Density and Vertebral Fractures in Men 总被引:1,自引:0,他引:1
E. Legrand D. Chappard C. Pascaretti M. Duquenne C. Rondeau Y. Simon V. Rohmer M.-F. Basle M. Audran 《Osteoporosis international》1999,10(4):265-270
In women, many studies indicate that the risk of vertebral fragility fractures increases as bone mineral density (BMD) declines.
In contrast, few studies are available for BMD and vertebral fractures in men. It is uncertain that the strength of the relationship
between BMD and fractures is similar in magnitude in middle-aged men and in postmenopausal women. In the present study, 200
men (mean age 54.7 years) with lumbar osteopenia (T-score <−1.5) were recruited to examine the relationships between spine BMD and hip BMD and the associations of BMD with vertebral
fractures. Lumbar BMD was assessed from L2 to L4, in the anteroposterior view, using dual-energy X-ray densitometry. At the
upper left femur, hip BMD was measured at five regions of interest: femoral neck, trochanter, intertrochanter, Ward’s triangle
and total hip. Spinal radiographs were analyzed independently by two trained investigators and vertebral fracture was defined
as a reduction of at least 20% in the anterior, middle or posterior vertebral height. Spinal radiographs evidenced at least
one vertebral crush fracture in 119 patients (59.5%). The results of logistic regression showed that age, femoral and spine
BMDs were significant predictors of the presence of a vertebral fracture. Odds ratios for a decrease of 1 standard deviation
ranged from 1.8 (1.3–2.8) for spine BMD to 2.3 (1.5–3.6) for total hip BMD. For multiple fractures odds ratios ranged from
1.7 (1.1–2.5) for spine BMD to 2.6 (1.7–4.3) for total hip BMD. In all models, odds ratios were higher for hip BMD than for
spine BMD, particularly in younger men, under 50 years. A T-score <−2.5 in the femur (total femoral site) was associated with a 2.7-fold increase in the risk of vertebral fracture while
a T-score <−2.5 in the spine was associated with only a 2-fold increase in risk. This study confirms the strong association of
age and BMD with vertebral fractures in middle-aged men, shows that the femoral area is the best site of BMD measurement and
suggests that a low femoral BMD could be considered as an index of severity in young men with lumbar osteopenia.
Received: 27 October 1998 / Accepted: 22 February 1999 相似文献