Androgen receptor (AR) gene microsatellite polymorphism in postmenopausal women: correlation to bone mineral density and susceptibility to osteoporosis

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.     

The ALUI calcitonin receptor gene polymorphism (TT) is associated with low bone mineral density and susceptibility to osteoporosis in postmenopausal women

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.     

Association of CYP1A1 and CYP1B1 polymorphisms with bone mineral density variations in postmenopausal Mexican-Mestizo women

Herein, we investigated potential associations between polymorphisms of genes related to estrogen metabolism and bone mineral density (BMD) in postmenopausal women. This was a cross-sectional study, in which two hundred and ninety postmenopausal Mexican-Mestizo women were studied. The BMD of the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured. The distribution of the genetic polymorphisms, including rs1799814 and rs1048943 at CYP1A1 as well as rs1056836 at CYP1B1, were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP), single-stranded conformational polymorphism (SSCP), and DNA sequencing. Deviations from Hardy–Weinberg equilibrium (HWE) were tested, and linkage disequilibrium (LD) was calculated by direct correlation (r²). Moreover, haplotype analysis was performed. All polymorphisms were in HWE. The genotype and allele distributions of the three single nucleotide polymorphisms (SNPs) studied showed no significant differences. However, statistical significance was reached when constructing haplotypes. The CG haplotype in CYP1A1 was associated with variations in LS and FN BMD after adjustment for covariates (p?=?0.021 and 0.045, respectively), but the association with TH BMD was not significant. These results suggested that the CG haplotype in CYP1A1 may play an important role in the mechanism of osteoporosis and may be useful as a genetic marker.     

Hot flushes, bone mineral density, and fractures in older postmenopausal women

OBJECTIVE: To assess whether greater severity of hot flushes is associated with bone loss or fracture risk in older postmenopausal women. METHODS: This study is a secondary analysis of 3,167 postmenopausal women in the Multiple Outcomes of Raloxifene Evaluation trial. Baseline hot flush severity was assessed by self-report. Femoral neck and lumbar spine bone density was assessed by dual-energy X-ray absorptiometry. Vertebral and nonvertebral fractures were determined radiographically and by interview. Baseline bone density, 3-year bone loss, baseline prevalent fractures, and 3-year fracture incidence were examined in women with varying hot flush severity. RESULTS: After adjusting for other characteristics, greater severity of hot flushes was associated with higher, rather than lower, baseline bone density (adjusted mean femoral neck bone density=0.633, 95% confidence interval [CI] 0.614-0.652 g/cm2, versus 0.611, 95% CI 0.608-0.613 g/cm2 for women with "severe" versus "minimal" hot flushes). Women with more severe hot flushes were less likely to have a baseline fracture (odds ratio 0.64, 95% CI 0.48-0.84, for vertebral fracture in women with moderate or severe versus minimal hot flushes). The 3-year annualized change in bone density did not differ among women with varying hot flush severity (P>.40 for all). Hot flush severity was not related to incident vertebral or nonvertebral fracture (P>.05 for all). CONCLUSION: Among osteoporotic women who are 5 or more years postmenopausal, greater severity of persistent hot flushes is not associated with progressive bone loss or risk of fracture, despite previous research linking hot flushes to bone loss during early menopause. LEVEL OF EVIDENCE: II.     

Effect of specific exercise training on bone mineral density in women with postmenopausal osteopenia or osteoporosis

Aim.?To analyse the effect of a specific program of weight training exercise with closed kinetic chain in bone mineral density in postmenopausal women with osteopenia or osteoporosis.

Methods.?A total of 59 postmenopausal women with osteoporosis or osteopenia were included in this prospective study. Subjects were divided into two groups: the study group (SG, n = 30; 57.5 ± 5.1 years) and the control group (CG, n = 29; 56.6 ± 4.6 years). In the study group was applied a weight exercise protocol (longitudinal forces in closed kinetic chain) during 12 months, whereas in the control group no weight exercise protocol was applied. Bone mineral density at the lumbar spine and hip was assessed at baseline and at the end of follow-up by dual energy X-ray absorptiometry.

Results.?Although no significant intragroup differences were found, patients in SG showed a 1.17% increase in the lumbar spine whereas in CG a 2.26% decrease in bone density was detected.

Conclusion.?This protocol of weight training exercise did not significantly improve bone mineral density in postmenopausal women with osteopenia or osteoporosis, but in comparison to the control group, the results showed the importance of practising the specific exercise program for maintenance of bone health in postmenopausal women.     

北京地区汉族绝经后妇女雌激素受体基因多态性与尺桡骨骨密度相关性研究

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。     

Serum lipid levels and bone mineral density in Greek postmenopausal women

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.     

The association of RANK gene C421T and C575T polymorphisms with bone mineral density in postmenopausal Turkish women

Purpose

To investigate the association between C421T polymorphism within exon 4, C575T polymorphism within exon 6 of the RANK gene and bone mineral density (BMD) variations in postmenopausal Turkish women.

Methods

One hundred seventy-eight postmenopausal women (patients = 100 and controls = 78) who applied to Ege University Faculty of Medicine, Department of Physical Medicine and Rehabilitation, for osteoporosis examination were analyzed. BMDs of the lumbar spine and femoral sites were measured. Patient and control groups were established based on their T-score values being above and/or below ?1. After venous blood sampling, C421T and C575T polymorphisms of the RANK gene were assessed through PCR process following DNA extraction.

Results

Genotype frequencies for the C421T and C575T polymorphisms were compared between the control group and the patient group. No significant difference was detected between the two groups for both polymorphisms. There was also no significant difference between the control and patient groups in terms of the combined genotype (p = 0.752) and the combined haplotype analysis of the C421T and C575T polymorphisms (p = 0.723). In the control and patient groups separately, no significant differences in BMD values either at the femoral sites or at the lumbar spine were detected between the combined genotypes of the two polymorphisms.

Conclusions

The genotypes, combined genotypes and allele frequencies of C421T and C575T polymorphisms of the RANK gene have not been found to be associated with BMD in Turkish women. Further studies including both sexes and more cases are required.     

Relation of vitamin D receptor FokI start codon polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal women in Taiwan

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.     

Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women

OBJECTIVE: To evaluate the effects of dietary isoflavones in soy products on menopausal symptoms, lipid profiles, and bone mineral densities in postmenopausal Japanese women. METHODS: We estimated the daily intakes of isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption. We recorded serum values of fasting total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoproteins. Bone mineral density was measured at the lumbar spine (L2-L4) by dual energy x-ray absorptiometry. Women were assigned to two groups according to years since menopause (early and late postmenopausal groups), and each group was subcategorized into four groups according to dietary isoflavone intake. Relationships between isoflavone intake, menopausal symptoms, lipid profiles, and bone mineral density were examined in each group. RESULTS: The mean estimated intake of isoflavones among 478 women was 54.3 mg/day. With stepwise regression analysis we found that weight and years since menopause were significant independent predictors of bone mineral density. Bone mineral densities adjusted to years since menopause and weight were significantly different in the highest intake compared with lowest intake category (P <.001) within the early and late postmenopausal groups. In the early postmenopausal group, significant differences were found in palpitation and backaches between the high and low intake categories but were not significant in the late postmenopausal group. CONCLUSION: High consumption of soy products is associated with increased bone mass in postmenopausal women and might be useful for preventing hypoestrogenic effects.     

Relationship between serum leptin concentrations and bone mineral density as well as biochemical markers of bone turnover in women with postmenopausal osteoporosis

OBJECTIVE: To determine whether leptin is involved in bone remodeling in patients with postmenopausal osteoporosis. DESIGN: Cross-sectional study. SETTING: Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University. PATIENT(S): Ninety postmenopausal osteoporotic women (37 obese and 53 nonobese) and 30 healthy premenopausal women from the same clinic served as controls. Lumbar spine bone mineral density (LS-BMD) of osteoporotic patients was more than 2.5 SD below the normal mean of healthy premenopausal women. MAIN OUTCOME MEASURE(S): Serum levels of leptin, osteocalcin (OC), bone alkaline phosphatase (B-ALP), urinary deoxypyridinoline (DPyr), and N-telopeptide of type 1 collagen (NTX) as well as LS-BMD using dual energy X-ray absorptiometry (DEXA). RESULT(S): The serum leptin level in obese postmenopausal osteoporotic patients was significantly increased compared with nonobese osteoporotic patients. There were no significant differences of bone formation markers (B-ALP, OC), bone resorption markers (DPyr, NTX), or LS-BMD between the obese and nonobese groups. There were no significant correlations between serum leptin and any biomarkers of bone turnover and BMD. CONCLUSION(S): In postmenopausal osteoporotic patients with increased bone turnover, serum leptin concentration is not correlated with BMD or with the biomarkers of bone formation or bone resorption.     

Association of vitamin D receptor gene polymorphism with bone mineral density in Slovenian postmenopausal women.

Osteoporosis is a common bone disease which affects one in three women after the 60th year of life and is a major cause of morbidity in older people. To identify patients with osteoporosis, measurement of bone mineral density (BMD) is recommended. The association of BMD with vitamin D receptor (VDR) genotype in Slovenian postmenopausal women was studied. We determined VDR genotype in 102 late postmenopausal women aged 47-77 years. BMD measurements were performed at the level of the lumbar spine (L2-L4) by dual X-ray absorptiometry. Our data show significantly lower BMD in BB women compared to those with bb genotype. The relative distribution of VDR genotypes and alleles in the Slovenian population was 18.6:57.8:23.6% for BB:Bb:bb, respectively. The results are consistent with those of a previous study which found an excellent correlation between BB VDR genotype and low BMD. The data were derived from a relatively small, but ethnically homogeneous population of the same socioeconomic status, with very similar dietary and physical activity habits. Dietary habits in particular seem to be important because of the relatively low calcium intake which may enhance the phenotypic expression of VDR gene polymorphisms.     

Genetic polymorphism of the calcitonin receptor gene and bone mineral density in Polish population of postmenopausal women

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.     

Correlations of serum prolidase activity between bone turnover markers and mineral density in postmenopausal osteoporosis

Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation. The aim of this study was to evaluate the serum prolidase activity and its relationship between bone turnover markers and bone mineral density (BMD) in postmenopausal osteoporosis. The study included 45 postmenopausal osteoporotic, 55 postmenopausal nonosteoporotic and 38 premenopausal healthy women. BMD was measured at the femoral neck and lumbar spine with DEXA. T score was more than 2.5 SD below the normal at the lumbar spine or femoral neck in postmenopausal osteoporotic patients. Serum levels of prolidase, C-terminal telopeptide of type I collagen (C-telopeptide), total alkaline phosphatase (ALP), osteocalcin (OC), urinary deoxypyridinoline (Dpd) and urinary creatinine were also assayed. C-telopeptide, total ALP, OC, urinary Dpd levels were significantly higher in postmenopausal osteoporotic group compared with premenopausal women. However, there was no statistical difference in serum prolidase activity between the three groups. There were also no significant correlations between serum prolidase and any biomarkers of bone turnover as well as BMD. To conclude, in postmenopausal osteoporotic women with increased bone turnover, serum prolidase concentration was not correlated with the biomarkers of bone formation or bone resorption and with BMD.