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OBJECTIVES: Osteoporosis is a multifactoral disease with aetiology depending from the hormonal, environmental, and genetic factors. One of the suggested candidate gene involved in the pathogenesis is the polymorphic gene encoding for vitamin D receptor (VDR). VDR polymorphism was connected with bone mineral density (BMD) and correlated with onset of osteoporosis. The goal of our study was to determine the role of BsmI polymorphism of VDR gene in the group of postmenopausal women with low bone mineral density. MATERIALS AND METHODS: We have analysed the group of 34 postmenopausal women. The DNA analysis was performed using PCR/RFLP (polymerase chain reaction/restriction fragment length polymorphism) assays. RESULTS: In our investigation we have observed statistically higher frequency of B allele (48.5% vs. 41.2%), the lower frequency of b allele (51.5% vs. 58.8%) and bb genotype (8.8% vs. 42.5%) in the investigated group of postmenopausal women with low BMD. CONCLUSIONS: Our observations could suggest the important role of B allele of the VDR gene in the pathogenesis of osteoporosis in the group of women with low mineral density and possible protective role of b allele in this disease.  相似文献   

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OBJECTIVE: We studied whether vitamin D receptor and estrogen receptor gene polymorphism is associated with the effect of hormone replacement therapy on lumbar-spinal bone mineral density in Japanese women. STUDY DESIGN: The subjects were 82 Japanese women aged 40 to 64 years (49.7 +/- 0.6 years, mean +/- SEM) who had taken hormone replacement therapy for >1 year. Genomic deoxyribonucleic acid was extracted from blood and analyzed for restriction fragment length polymorphism with the restriction endonucleases Taq I, Apa I, and Fok I for vitamin D receptor and Pvu II and Xba I for estrogen receptor. RESULTS: The subjects with genotype TT had a significantly higher percentage change in bone mineral density per year than those with the Tt genotype (2.8% +/- 0.6% vs -0.8% +/- 1.4%, P =.019). The serum level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen decreased by 13% during 1 year of hormone replacement therapy in subjects with the TT genotype (P =. 001) but did not change in women with the Tt genotype. In multiple regression analysis including age, height (centimeters), weight (kilograms), and polymorphisms of the vitamin D receptor and estrogen receptor genes, only age and Taq I polymorphism of the vitamin D receptor gene were associated independently with change in bone mineral density (P =.001 and.004, respectively). CONCLUSION: Taq I polymorphism of the vitamin D receptor gene is associated with the effect of hormone replacement therapy on lumbar-spinal bone mineral density and bone resorption markers in Japanese women. Analysis of the vitamin D receptor alleles may prove useful for selection of the optimum therapy for osteoporosis management.  相似文献   

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OBJECTIVES: The objective of the study was to evaluate the effect of vitamin D receptor (VDR) gene haplotypes on bone mineral density (BMD). STUDY DESIGN: The VDR Bsm I, Apa I, Taq I, and poly(A) polymorphisms were analyzed in 417 postmenopausal Korean women. Serum 1,25(OH)(2) vitamin D(3), osteocalcin, bone alkaline phosphatase, and CrossLaps were measured by immunoradiometric assay and enzyme-linked immunosorbent assay. BMD at the lumbar spine and proximal femur was determined by dual-energy x-ray absorptiometry. RESULTS: At all skeletal sites, genotypes not carrying the baTL haplotype allele (uppercase letters signifying the absence, lowercase letters the presence, of the restriction site, and L a repeat length of more than 17) had significantly lower BMD than baTL homozygotes. The former genotypes were more prevalent in women with low bone mass than in healthy women. No significant differences in vitamin D(3) or bone markers levels were noted among the baTL haplotype genotypes. CONCLUSION: The VDR baTL haplotype allele is related to bone mass in Korean women.  相似文献   

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BACKGROUND: Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of the vitamin D receptor FokI start codon polymorphism to bone mineral density and the occurence of osteoporosis. METHODS: We determined the vitamin D receptor FokI start codon polymorphism using polymerase chain reaction-based restriction analysis in 163 postmenopausal women in Taiwan. The vitamin D receptor gene polymorphism was detected by the restriction enzyme FokI, where the F allele indicated the absence of the cuttable site and the f allele its presence. We then related the genotypes to bone mineral density and the occurence of osteoporosis in these women. RESULTS: The allelic frequencies for 163 postmenopausal women in Taiwan were 59.2% for F and 40.8% for f in FokI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was: 42.3% FF, 33.7% Ff and 24% ff. The three genotypic groups differed significantly in bone mineral density at the lumbar spine (P = 0.029). Bone mineral density was highest in the Ff group and lowest in the ff group at the lumbar spine and the femoral neck. The FokI vitamin D receptor genotype showed a significant effect on the prevalence of osteoporosis in the subjects at the lumbar spine. That is, women with genotype ff had a 2.8 times greater risk for osteoporosis (P < 0.05), and those with genotype FF had a 0.8 times greater risk than women with genotype Ff. CONCLUSION: Our findings indicate that the vitamin D receptor FokI start codon polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis at the lumbar spine.  相似文献   

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INTRODUCTION: In recent years the influence of genetic factors in the pathogenesis of osteopenia and osteoporosis was indicated. The investigations focused on the gene coding for calcitonin receptor. The goal of our analysis was to determine the genotype frequencies of AluI polymorphism of the calcitonin receptor gene (CTR) in the group of Polish postmenopausal women and its possible contribution to osteoporosis development. MATERIAL AND METHODS: 139 postmenopausal women with osteopenia (t-score value from -1.0 to -2.5) (mean age 58.5 +/- 5.9 years, mean age of menopause 49.8 +/- 3.9 years) have been investigated. AluI polymorphism of the CTR gene was determined using PCR/RFLP assay. We have analysed 3 subgroups: CC, CT, and TT. In each subgroup mean weight, height, body mass index (BMI), mean age of menopause and years since menopause (YSM) and parameters of bone turnover: bone mineral density (BMD), t-score, index: young adults (YA) and--age matched (AM) have been analysed. Additionally the group of 138 selected women (mean age 26.5 +/- 4.3 years) as general population has been analysed. RESULTS: In investigated group the frequency of all 3 genotypes was determined as follows: CC: CT : TT = 8.6 : 45.3 : 46.1. Analysing BMD in particular subgroups the higher value for the CT genotype (0.967 +/- 0.161 g/cm2) was found. Similarly t-score (-1.94), YA (80.6%) and AM (90.8%) index were higher in CT genotype carriers. CONCLUSION: Our results suggest possible connection of the AluI polymorphism of the CTR gene with osteopenia and osteoporosis development. To confirm this tendency further investigations in the large number population are necessary.  相似文献   

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AIMS: This study examined whether or not a decrease in bone mineral density (BMD) induced by the use of gonadotropin-releasing hormone agonist (GnRHa) during sexual maturation is affected by vitamin D receptor and/or estrogen receptor gene polymorphisms, like the phenomenon observed during the postmenopausal period. METHODS: In 43 patients who received GnRHa therapy for 6 months to treat uterine myoma or endometriosis at our department and who were confirmed to have pituitary down-regulation, we measured bone density before and after GnRHa treatment using DXA and analyzed the bone metabolism turnover using bone metabolic markers. Polymorphisms were analyzed by RFLP using FokI and TaqI for the vitamin D receptor gene and PvuII and XbaI for the estrogen receptor gene. The then determined gene polymorphism was analyzed in relation to the percentage decreases in BMD following GnRHa treatment. RESULTS: The patients were divided by f, t into two groups: (f, t) < 2 (Group V-I) and (f, t) > or = 2 (Group V-II). They were also divided by P, x into two groups (P, x) < 3 (Group E-I) and (P, x) > or = 3 (Group E-II). The BMD change was significantly higher in Group V-II than in Group V-I. Group E-II tended to have a higher BMD change than Group E-I, although this difference was not statistically significant. CONCLUSION: Patients who often have f and t polymorphism are more likely to show BMD reduction following GnRHa therapy, like the phenomenon seen during the postmenopausal period, than patients with other gene polymorphisms. Measures to avoid BMD reduction are required when using GnRHa in such patients.  相似文献   

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The aims of the study were as follows: (1) To identify the differences in spinal body mass density (BMD) in relation to polymorphism in vitamin D receptor (VDR) and estrogen receptor-α (ERα) genes in untreated women with postmenopausal osteoporosis. (2) To assess the efficacy of treatment in women with postmenopausal osteoporosis in relation to polymorphism in VDR and ERα genes. (3) To find the estradiol concentration necessary to protect bone tissue in patients with a given polymorphism in VDR and ERα genes.

Methods.?The study included 44 postmenopausal women with primary osteoporosis who used cyclic hormonal replacement therapy (HRT) for a year. The polymorphism of ERα and VDR genes were evaluated. We also determined the age, body mass index and spinal BMD before and after 12 months of administration the HRT.

Results.?We found a significant spinal BMD increase, what is connected with ERα genotype and both VDR and ERα genes. There is no such a correlation observed in polymorphism of VDR gene.

Conclusions.?(1) There is no relationship between VDR and ERα genes polymorphism and the stage of osteoporosis related to the spinal BMD value before treatment. (2) The XX, PP or Bb markers or only X, P, B alleles are connected with a significant decrease of treatment efficacy. (3) Estradiol serum concentration before and during HRT is not dependent on the polymorphism of VDR and ERα genes.  相似文献   

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Background

The relationship of homocysteine (Hcy), folate, and vitamin B12 with bone mineral density (BMD) has been investigated in postmenopausal women. However, the relationship is still controversial.

Purpose

To evaluate the association of Hcy, folate, vitamin B12 and BMD in postmenopausal women with a meta-analysis.

Methods

We searched for all published articles indexed in Medline (1950–2012), Embase (1974–2012), and China National Knowledge Infrastructure (1994–2012). Any case–control or cohort study relating to Hcy, vitamin B12, folate, and BMD was included, and the data were extracted independently by two reviewers. Criteria for inclusion were the assessment of Hcy, vitamin B12, folate, and BMD in postmenopausal women as outcomes. We performed this meta-analysis with Review Manager 5.1 software. Odds ratios and 95 % confidence intervals (CI) were used to evaluate the results.

Results

Six eligible studies were selected for meta-analysis. Our analysis suggested that vitamin B12 and Hcy levels were significantly higher in postmenopausal osteoporosis (PMOP) group than that in controls (P = 0.007, <0.05; 95 % CI 3.06–19.38 and P = 0.0003, <0.05; 95 % CI 0.75–2.52, respectively). Folate level was lower in PMOP group than that in controls, but this difference was not statistically significant (P = 0.09, 95 % CI ?3.33 to 0.25).

Conclusions

Hcy and vitamin B12, but not folate, were related to BMD in PMOP. Extra vitamin B12 may not play a protective role for osteoporosis in postmenopausal women. Future studies are needed to confirm them, especially the relationship between increased vitamin B12 and BMD.  相似文献   

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OBJECTIVE: To investigate the correlation of the androgen receptor gene microsatellite polymorphism (CAG trinucleotide repeat polymorphism on exon 1) with bone mineral density and their relationship to osteoporosis in postmenopausal women. STUDY DESIGN: A number of 168 of 477 postmenopausal women were randomly recruited. The androgen receptor gene microsatellite polymorphism was determined using polymerase chain reaction-based microsatellite analysis. Bone mineral density of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry. RESULTS: The AR genotype was classified from "9" to "32" according to the number of CAG trinucleotide repeats they contained to represent "signposts". After adjustment for potential confounding factors such as age, height, weight, years since menopause, and daily calcium intake, subjects with genotype 20+ (n=64) had lower bone mineral density values and a significantly greater risk for osteoporosis (OR 4.2, 95% CI 1.0-17.2) when compared with subjects with genotype 20- (n=104) at the femoral neck. CONCLUSION: The present study suggests that the androgen receptor gene microsatellite polymorphism may be a candidate genetic marker for risk of osteoporosis in postmenopausal women.  相似文献   

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目的 研究雌激素受体(ER)基因多态性在北京地区汉族绝经后妇女中的分布及其与骨密度的相关性。方法 对绝经1~4年、年龄49~55岁未行激素替代治疗且无对骨密度有影响疾病的健康绝经后北京市区汉族妇女99例,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定ER基因的XbaⅠ和PvuⅡ酶切多态性,用双能X线吸收测量法检测桡骨骨密度(以骨密度T-score值表示),方差法分析ER基因多态性与骨密度的关系。结果 ER基因PvuⅡ酶切多态性与尺桡骨松质骨(尺桡骨远端)、密质骨(尺桡骨近端)的骨密度无相关性(P>0.05),而ER基因XbaⅠ酶切多态性与尺、桡骨松质骨、密质骨的骨密度有相关性(P<0.05);XX基因型骨密度值最低密质骨为-1.55±0.37、松质骨为-2.54±0.38,xx基因型骨密度值最高密质骨为-0.95±0.24、松质骨为-1.74±0.16。结论 ER基因XbaⅠ酶切多态性与尺、桡骨松质骨、密质骨的骨密度间显著相关,不同个体的基因差异可能影响骨质疏松症的发生、发展。  相似文献   

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Osteoporosis is a common disorder with a strong genetic component. Our aim was to evaluate the correlation of the ALUI calcitonin receptor gene polymorphism to bone mineral density and their relationship to osteoporosis. We determined the ALUI calcitonin receptor gene polymorphism using polymerase chain reaction-based restriction analysis in 167 postmenopausal women in Taiwan. The polymorphism was detected by the restriction enzyme ALUI, where the C allele indicated the absence of the cuttable site and the T allele indicated its presence. Bone mineral density of the lumbar spine and proximal femur were measured using dual-energy X-ray absorptiometry. The allelic frequencies for the 167 postmenopausal women in Taiwan were 86.5% for C and 13.5% for T in ALUI restriction fragment length polymorphisms. The prevalence of each genotype in the study population was 2.4% TT, 22.2% CT, and 75.4% CC. The three genotypic groups differed significantly in unadjusted and adjusted bone mineral density at the lumbar spine and the femoral neck. Unadjusted and adjusted bone mineral density values were lowest in women with the TT genotype. The ALUI calcitonin receptor genotype showed a positive association with prevalence of osteoporosis in the subjects. That is, women with genotype TT had a greater risk for developing osteoporosis at the lumbar spine and at the femoral neck. The ALUI calcitonin receptor gene polymorphism is associated with reduced bone mineral density and predisposes women to osteoporosis, but should be interpreted with caution because of the small number of subjects in the unfavorable TT genotype.  相似文献   

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Objective

To explore the associations between vitamin D receptor (VDR) gene polymorphisms (including Fok I, Bsm I and Apa I) and bone mineral density (BMD) in postmenopausal Asian women.

Study design

Databases of Medline, Embase and Wangfang were retrieved to identify eligible studies, with update to 1st February 2012. Standardized mean difference (SMD) and 95% confidence intervals were calculated by using fixed- or random-effect model. Best genetic comparison model was determined by using the Thakkinstian method.

Results

A total of 14 studies with 3243 healthy postmenopausal Asian women were included in this meta-analysis. Overall, pooled analyses indicated that the f allele of VDR Fok I was significantly associated with decreased BMD in the lumbar spine (ff vs. FF: SMD (95% CI): −0.87 (−1.38, −0.35); P = 0.001 for lumbar spine; −0.43 (−0.93, 0.06), P = 0.086 for femoral neck). In contrast, we did not observe overall associations between VDR Bsm I and Apa I polymorphisms and BMD in either lumbar spine or femoral neck (Bsm I bb vs. BB: SMD (95% CI): 0.61 (−1.30, 2.53), P = 0.531 for lumbar spine; Apa I aa vs. AA: SMD (95% CI): 0.66 (−0.16, 1.48), P = 0.113 for lumbar spine). When subgroup analyses were conducted according to countries, Indians carrying the VDR Fok I ff genotype were at risk of low BMD at lumbar spine (ff vs. FF: SMD (95% CI): −0.57 (−0.85, −0.29), P < 0.001). Sensitivity analyses indicated that no single study had substantial influence on all combined analyses. In addition, no publication bias was identified.

Conclusions

This meta-analysis indicated that VDR Fok I, rather than Bsm I and Apa I polymorphisms, is associated with bone mineral density in postmenopausal Asian women (especially for Indian women), and can probably be used with other genetic markers together to identify individuals at high risk of osteoporosis.  相似文献   

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目的研究维生素D受体基因多态性与0~6岁汉族儿童骨密度(BMD)的关系,为临床儿童低BMD的早期预防提供理论依据。 方法上海新华医院上海市儿科医学研究所2002年7月至2004年3月收集排除影响骨代谢疾病的上海地区0~6岁汉族儿童204例,进行问卷调查、体格测量;用原子吸收分光光度计测血清锌;用放射免疫法测血清25(OH)D3;用超声BMD仪测定胫骨中段骨密度;用聚合酶链反应 限制性片段长度多态性方法,分析4个限制性酶切位点(ApaI、TaqI、BsmI、FokI)的多态分布。用多因素协变量方差分析维生素D受体(VDR)基因多态性与BMD的关系。 结果多因素协方差分析消除血清25(OH)D3水平、血清锌水平、户外体育活动等因素对BMD的影响后,发现VDR基因BsmI酶切位点等位基因型和FokI酶切位点等位基因型与BMD相关,Bb基因型的BMD百分位数明显低于bb基因型,分别为2200%和4314%,差异有显著性(F=504,P<005);ff基因型骨密度低于Ff与FF基因型,分别为2697%、3795%、5352%,差异有极显著性(F=811,P<0001)。而在Apa I、Taq I酶切位点,不同等位基因型与BMD无关(F=108、127,P>005)。 结论VDR基因在BsmI、FokI酶切位点的多态性与0~6岁汉族儿童BMD相关。  相似文献   

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Objective: Present study was designed to find out whether leptin is a predictor of bone mass density (BMD) in premenopausal women (PMW) and postmenopausal osteoporotic women (PMOPW) or it has no association with BMD.

Methods: One hundred and ninety two women (98 PMOPW and 94 PMW) were recruited for this study. The control group was BMI matched with osteoporotic subjects. BMD assessment was done on calcaneus by peripheral ultrasound bone densitometry and T scores were determined. Serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Serum leptin and BMD values were significantly different in both groups (leptin, 18.56?±?8.65?ng/ml versus 21.64?±?9.80?ng/ml, p?=?0.02) and (BMD, ?0.70?±?0.19 versus ?3.17?±?0.59, p?=?0.000), respectively. In PMOPW serum leptin and BMD were considerably correlated with weight (lep, r?=?0.53, p?=?<0.001; BMD, r?=??0.21, p?=?0.02), BMI (lep, r?=?0.52, p =?<0.001; BMD, r?=??0.27, p?=?0.005), waist circumference (lep, r?=?0.61, p?=?<0.001; BMD, r?=?0.18, p?=?0.04), hip circumference (lep, r?=?0.58, p?=?<0.001).

Multivariate linear stepwise regression analysis showed that weight and BMI in PMW and PMOPW were independent predictors of BMD. Serum leptin level was not found to be the predictor of BMD in both groups.

Conclusion: The present results indicate that body weight and BMI have an impact on BMD while serum leptin is not associated with BMD in PMW and PMOPW.  相似文献   

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A double-blind, placebo-controlled, randomized, prospective two-center study was carried out to assess the effects of tibolone + fluoride versus placebo + fluoride therapy on trabecular and cortical bone in postmenopausal osteoporotic women. Ninety-four subjects (mean age 61.1 years, postmenopausal 13.5 years on average) with low bone mineral density (BMD) at baseline were randomized to 2.5 mg of tibolone (Org OD 14, Livial) plus 26.4 mg of fluoride (Fluocalcic) or placebo plus 26.4 mg of fluoride daily over 2 years; 55 (58.5%) subjects completed the study, the main reason for discontinuation being untoward gastrointestinal effects. BMD at the lumbar spine was measured by both dual photon absorptiometry (DPA) and dual-energy X-ray absorptiometry (DXA), and at the hip by DXA at 6-month intervals. Baseline values (DXA, g/cm2) for tibolone + fluoride and placebo + fluoride groups were 0.733 and 0.744 for the lumbar spine, and 0.761 and 0.788 for the hip. Change from baseline and percentage change from baseline were calculated for the intent-to-treat and completers groups. An analysis of variance (ANOVA) model or Wilcoxon test was used for statistical evaluation. There was a mean increase in BMD at the lumbar spine measured by DPA of 25.3% and 12.3% in tibolone + fluoride and placebo + fluoride groups, respectively (p = 0.01); with DXA, respective changes were 32.6% and 14.0% (p = 0.013). Data on BMD at the hip showed mean increases of 7.9% and 2.6% for the tibolone + fluoride and placebo + fluoride groups, respectively. We conclude that combined tibolone + fluoride treatment induces a highly significant increase in BMD at the lumbar spine without simultaneous loss of the cortical bone allowing for a meaningful reduction of the fluoride dose when given in combination with tibolone.  相似文献   

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Aim. Vitamin D could have a direct effect on adipocyte differentiation and metabolism and might be involved in glucose regulation of insulin secretion. In recent years several polymorphisms in the gene encoding the vitamin D receptor (VDR), which are potent to alter the activity of VDR protein, have been described. The present study aimed to investigate the prevalence of the VDR BsmI polymorphism and its association with anthropometric and biochemical features of metabolic syndrome in postmenopausal women.

Materials and methods. We studied 351 randomly selected healthy postmenopausal women, with mean age of 55.43 ± 2.75 years and mean body mass index (BMI) of 27.5 ± 4.78 kg/m2, to evaluate the frequency of BsmI polymorphism (by restriction fragment length polymorphism–polymerase chain reaction) in the VDR gene and to find out whether there is an association between this polymorphism and BMI, total fat volume and visceral fat (as determined by total body dual-energy X-ray absorptiometry), blood pressure, lipid profile (total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides) glucose and fasting insulin in the whole group, as well as subgroups of obese and non-obese women.

Results. The prevalence of BsmI genotypes in the study group was 51.0% Bb, 37.3% bb and 11.7% BB. Genotype distribution did not differ from that expected under Hardy–Weinberg equilibrium conditions (χ2 = 2.95, p = 0.22). Apart from LDL-C levels (F = 3.46, p = 0.032), there were no significant differences in anthropometric or metabolic parameters between genotypes.

Conclusions. The BsmI polymorphism in the VDR gene does not seem to predispose to obesity and insulin resistance, but the BB genotype is connected with an unfavorable lipid profile.  相似文献   

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Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X-ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non-significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age ≥ 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements.  相似文献   

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