Risk Of Postmenopausal Osteoporosis Research Articles

IL-16 Mediates the Effect of Circulating Metabolites on Postmenopausal Osteoporosis: A Two-Step, Multivariable Mendelian Randomization Study.

Objectives: This study aimed to explore the relationship between circulating metabolites and postmenopausal osteoporosis (PMOP) and to assess the mediating role of inflammatory factors. Methods: Utilizing summary-level data from genome-wide association studies (GWAS) and employing a Mendelian Randomization approach, a two-sample MR analysis was conducted to assess the relationship between circulating metabolites and PMOP. Additionally, a two-step MR was used to quantify the mediating impact of inflammatory factors on the effect of circulating metabolites on PMOP. Results: The results revealed a significant association between certain metabolites and the risk of PMOP, notably the ratio of free cholesterol to total lipids in very large VLDL particles (OR: 1.399, 95% CI: 1.002-1.954, p = 0.048) and IL-16 (OR: 0.773, 95% CI: 0.608-0.983, p = 0.036). IL-16 was found to partially mediate the impact of circulating metabolites on PMOP, with a mediation effect of 10.4%. Conclusion: This study underscores the crucial role of circulating metabolites and inflammatory factors in PMOP pathogenesis. A causal relationship between circulating metabolites and PMOP was established, with IL-16 mediating some effects. These findings hold promise for clinical applications in early detection, personalized medicine, and the identification of therapeutic targets for PMOP.

Vascular endothelial growth factor I/D variant and postmenopausal osteoporosis risk in the Turkish population

Introduction Postmenopausal osteoporosis (PMOP) is a common metabolic bone disorder manifested by low bone mineral density and increased fracture risks in postmenopausal women. Vascular endothelial growth factor (VEGF) has been shown to play an important role in bone formation. In this study, we investigated the potential association between the VEGF insertion/deletion (I/D) variant (rs35569394) and PMOP in a cohort of postmenopausal Turkish women. Methods This study included 300 women, including 150 PMOP patients and 150 healthy postmenopausal women. A T score was used in the diagnosis of OP. DNA was extracted from all subjects. The VEGF I/D polymorphism was analyzed by the PCR method. The Hardy-Weinberg equilibrium (HWE) test and odds ratio (OR) were analyzed, considering CI 95% and p ≤ 0.05. Results The mean age of patients aged between 40 and 74 was 60.32 ± 8.65. The frequency of the I/I, I/D, and D/D genotypes was 7.34% versus 6.66%; 67.33% versus 65.34%; and 25.33% versus 28%, in patients and the control group, respectively. The allele frequencies were I: 41% (patients) and 39.4% (controls); D: 59% (patients) and 60.66% (controls). There was no statistically significant difference in the VEGF − 2549 I/D allele and genotype distribution between patients with PMOP and control subjects (p = 0.349, p = 0.864, respectively). Conclusion Our results showed that the VEGF I/D variant was not a significant factor in the development of PMOP in a Turkish population sample. These findings need confirmation in other ethnic populations.

Polymorphisms in the glucagon-like peptide-1 receptor gene and their interactions on the risk of osteoporosis in postmenopausal Chinese women.

Postmenopausal osteoporosis (PMOP) is a prevalent form of primary osteoporosis, affecting over 40% of postmenopausal women. Previous studies have suggested a potential association between single nucleotide polymorphisms (SNPs) in glucagon-like peptide-1 receptor (GLP-1R) and PMOP in postmenopausal Chinese women. However, available evidence remains inconclusive. Therefore, this study aimed to investigate the possible association between GLP-1R SNPs and PMOP in Han Chinese women. Thus, we conducted a case-control study with 152 postmenopausal Han Chinese women aged 45-80 years, including 76 women with osteoporosis and 76 without osteoporosis. Seven SNPs of the GLP-1R were obtained from the National Center of Biotechnology Information and Genome Variation Server. We employed three genetic models to assess the association between GLP-1R genetic variants and osteoporosis in postmenopausal women, while also investigating SNP-SNP and SNP-environment interactions with the risk of PMOP. In this study, we selected seven GLP-1R SNPs (rs1042044, rs2268641, rs10305492, rs6923761, rs1126476, rs2268657, and rs2295006). Of these, the minor allele A of rs1042044 was significantly associated with an increased risk of PMOP. Genetic model analysis revealed that individuals carrying the A allele of rs1042044 had a higher risk of developing osteoporosis in the dominant model (P = 0.029, OR = 2.76, 95%CI: 1.09-6.99). Furthermore, a multiplicative interaction was found between rs1042044 and rs2268641 that was associated with osteoporosis in postmenopausal women (Pinteraction = 0.034). Importantly, this association remained independent of age, menopausal duration, family history of osteoporosis, and body mass index. However, no significant relationship was observed between GLP-1R haplotypes and PMOP. In conclusion, this study suggests a close association between the A allele on the GLP-1R rs1042044 and an increased risk of PMOP. Furthermore, this risk was significantly augmented by an SNP-SNP interaction with rs2268641. These results provide new scientific insights into the development of personalized prevention strategies and treatment approaches for PMOP.

VDR gene ApaI polymorphism and risk of postmenopausal osteoporosis: a meta-analysis from 22 studies

Objective The ApaI polymorphism (G > T, rs7975232) of the vitamin D receptor (VDR) gene in the risk of postmenopausal osteoporosis has been widely researched, and the results have yielded conflicts. Therefore, we performed an updated pooled analysis to comprehensively assess the association between VDR ApaI polymorphism and postmenopausal osteoporosis risk. Methods We searched eligible studies about ApaI polymorphism and osteoporosis through the PubMed, Embase, CNKI and Wanfang databases; case–control studies containing available genotype frequencies of A/a were chosen. We used the odds ratio with 95% confidence interval to assess the strength of this association. Sensitivity analysis and publication bias assessment were performed. Trial sequential analysis (TSA) was performed to evaluate a sufficient sample. Results Twenty-two studies assessed the relationship between ApaI polymorphism and the risk of osteoporosis in postmenopausal women. The comprehensive analyses showed no significant association for ApaI polymorphism with postmenopausal osteoporosis in the overall population, equally valid for Asian and Caucasian subgroups with any genetic model. TSA still indicated the results were robust. Conclusion The present meta-analysis suggests that the VDR ApaI genotype may not affect the risk of postmenopausal osteoporosis in Asians and Caucasians.

Identification of a potential diagnostic signature for postmenopausal osteoporosis via transcriptome analysis.

Purpose: We aimed to establish the transcriptome diagnostic signature of postmenopausal osteoporosis (PMOP) to identify diagnostic biomarkers and score patient risk to prevent and treat PMOP. Methods: Peripheral blood mononuclear cell (PBMC) expression data from PMOP patients were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using the “limma” package. The “WGCNA” package was used for a weighted gene co-expression network analysis to identify the gene modules associated with bone mineral density (BMD). Least absolute shrinkage and selection operator (LASSO) regression was used to construct a diagnostic signature, and its predictive ability was verified in the discovery cohort. The diagnostic values of potential biomarkers were evaluated by receiver operating characteristic curve (ROC) and coefficient analysis. Network pharmacology was used to predict the candidate therapeutic molecules. PBMCs from 14 postmenopausal women with normal BMD and 14 with low BMD were collected, and RNA was extracted for RT-qPCR validation. Results: We screened 2420 differentially expressed genes (DEGs) from the pilot cohort, and WGCNA showed that the blue module was most closely related to BMD. Based on the genes in the blue module, we constructed a diagnostic signature with 15 genes, and its ability to predict the risk of osteoporosis was verified in the discovery cohort. RT-qPCR verified the expression of potential biomarkers and showed a strong correlation with BMD. The functional annotation results of the DEGs showed that the diagnostic signature might affect the occurrence and development of PMOP through multiple biological pathways. In addition, 5 candidate molecules related to diagnostic signatures were screened out. Conclusion: Our diagnostic signature can effectively predict the risk of PMOP, with potential application for clinical decisions and drug candidate selection.

Development and validation of a gene signature predicting the risk of postmenopausal osteoporosis.

AimsWe aimed to develop a gene signature that predicts the occurrence of postmenopausal osteoporosis (PMOP) by studying its genetic mechanism.MethodsFive datasets were obtained from the Gene Expression Omnibus database. Unsupervised consensus cluster analysis was used to determine new PMOP subtypes. To determine the central genes and the core modules related to PMOP, the weighted gene co-expression network analysis (WCGNA) was applied. Gene Ontology enrichment analysis was used to explore the biological processes underlying key genes. Logistic regression univariate analysis was used to screen for statistically significant variables. Two algorithms were used to select important PMOP-related genes. A logistic regression model was used to construct the PMOP-related gene profile. The receiver operating characteristic area under the curve, Harrell’s concordance index, a calibration chart, and decision curve analysis were used to characterize PMOP-related genes. Then, quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of the PMOP-related genes in the gene signature.ResultsWe identified three PMOP-related subtypes and four core modules. The muscle system process, muscle contraction, and actin filament-based movement were more active in the hub genes. We obtained five feature genes related to PMOP. Our analysis verified that the gene signature had good predictive power and applicability. The outcomes of the GSE56815 cohort were found to be consistent with the results of the earlier studies. qRT-PCR results showed that RAB2A and FYCO1 were amplified in clinical samples.ConclusionThe PMOP-related gene signature we developed and verified can accurately predict the risk of PMOP in patients. These results can elucidate the molecular mechanism of RAB2A and FYCO1 underlying PMOP, and yield new and improved treatment strategies, ultimately helping PMOP monitoring.Cite this article: Bone Joint Res 2022;11(8):548–560.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 μM). This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

Common variants in MAEA gene contributed the susceptibility to osteoporosis in Han Chinese postmenopausal women

BackgroundOsteoporosis (OP) is a complex bone metabolism disorder characterized by the loss of bone minerals and an increased risk of bone fracture. A recent study reported the relationship of the macrophage erythroblast attacher gene (MAEA) with low bone mineral density in postmenopausal Japanese women. Our study aimed to investigate the association of MAEA with postmenopausal osteoporosis (PMOP) in Han Chinese individuals.MethodsA total of 968 unrelated postmenopausal Chinese women comprising 484 patients with PMOP and 484 controls were recruited. Four tag single nucleotide polymorphisms (SNPs) that covered the gene region of MAEA were chosen for genotyping. Single SNP and haplotypic association analyses were performed, and analysis of variance was conducted to test the correlation between blood MAEA protein level and genotypes of associated SNPs.ResultsSNP rs6815464 was significantly associated with the risk of PMOP. The C allele of rs6815464 was strongly correlated with the decreased risk of PMOP in our study subjects (OR[95% CI]=0.75[0.63-0.89], P=0.0015). Significant differences in MAEA protein blood levels among genotypes of SNP rs6815464 were identified in both the PMOP (F=6.82, P=0.0012) and control groups (F=11.5, P=0.00001). The C allele was positively associated with decreased MAEA protein levels in blood.ConclusionThis case-control study on Chinese postmenopausal women suggested an association between SNP rs6815464 of MAEA and PMOP. Further analyses showed that genotypes of SNP rs6815464 were also associated with the blood level of MAEA protein.

Nutrient and Dietary Patterns in Relation to the Pathogenesis of Postmenopausal Osteoporosis-A Literature Review.

Postmenopausal women tend to be susceptible to primary osteoporosis due to its association with oestrogen deficiency. There is emerging evidence that an unhealthy dietary pattern drives an increase in the risk of postmenopausal osteoporosis (PO), whereas a healthy dietary pattern may decrease its occurrence. In this narrative literature review, we sought to review the role of nutrient and dietary patterns in the pathogenesis of PO. Therefore, we searched and reported all research articles from 2001 to May 2020 in Web of Science, Cinahl and Scopus that have researched a relationship between nutrient and/or dietary patterns and postmenopausal osteoporosis. Nutrients such as calcium, phosphorus, magnesium and vitamin D have been proven to be beneficial for bone health. Meanwhile, for the dietary patterns, foods such as dairy products especially milk, fibre and protein-rich foods, e.g., meat were directly linked to a positive association with bone mineral density (BMD). Likewise, fruits, vegetables and probiotic and prebiotic foods were reported for its positive relationship with BMD. Therefore, aside from physical activity, nutrition and diet in adequate proportions are suggested to be an important tool for ameliorating osteoporosis and bone health issues in older age.

Targeted next generation sequencing of nine osteoporosis-related genes in the Wnt signaling pathway among Chinese postmenopausal women.

This study aimed to explore the association between low-frequency and rare variants of Wnt signaling genes and postmenopausal osteoporosis (OP) by the next generation sequencing (NGS) technology. We performed targeted NGS of nine Wnt signaling genes in 400 Chinese postmenopausal women, including 226 cases with decreased bone mineral density (BMD) and 174 controls with normal values. Proxy External Controls Association Test (ProxECAT) and logistic regression analysis were performed by data from internal cases (n = 226) and Genome Aggregation Database (gnomAD) East Asian controls (n = 9435). The genomic region of interest (ROI) of 94 functional low-frequency and rare variants was associated with OP risk (P < 0.05). The LGR6 gene was associated significantly with OP risk and BMD measurements (BMD, T-score and Z-score) (adjusted-P < 0.05) after adjusting for confounders. The allele A of rs199693693 (K82N) in LRP6 and G of novel variant 1: 202287949 (R840G) in LGR6 were associated with higher BMD, T-score, and Z-score (all adjusted-P < 0.05). ProxECAT showed that LGR4 was significantly different between the internal cases and the external controls (all adjusted-P < 0.05). Logistic regression analysis revealed that the allele G of rs765778410 (T645A) (OR = 26.16, 95% CI: 4.36-156.95, adjusted-P value = 0.026) in LGR6 and A of rs61370283 (L987M) (OR = 15.39, 95% CI: 2.98-79.55, adjusted-P value = 0.037) in LRP5 were associated with increased risk of postmenopausal OP. The LGR4 and LGR6 genes and four potential functional rare variants associate with postmenopausal OP risk. These results highlight the significance of rare functional variants in postmenopausal OP genetics and provide new insights into the potential mutations in this field.

Association of Vitamin D Receptor Gene Variation With Osteoporosis Risk in Belarusian and Lithuanian Postmenopausal Women.

Vitamin D receptor (VDR) is one of the main mediators of vitamin D biological activity. VDR dysfunction might substantially contribute to development of postmenopausal osteoporosis (PMO). Numerous studies have revealed the effects of several VDR gene variants on osteoporosis risk, although significant variation in different ethnicities have been suggested. The main purpose of this work was to assess the frequency of distribution of VDR genetic variants with established effect and evaluate their haplotype association with the risk of PMO in a cohort of Belarusian and Lithuanian women. Case group included women with PMO (n = 149), the control group comprised women with normal bone mineral density (BMD) and without previous fragility fractures (n = 172). Both groups were matched for age, height, sex, and BMI—no statistically significant differences observed. VDR gene polymorphic variants (ApaI rs7975232, BsmI rs1544410, TaqI rs731236, and Cdx2 rs11568820) were determined using polymerase chain reaction and restriction fragment length polymorphism. The lumbar spine (L1-L4) and femoral neck BMD was measured using dual-energy X-ray absorptiometry. Association between each VDR variant and PMO risk was assessed using multiple logistic regression. The genotyping revealed statistically significant difference in the rs7975232 genotype frequencies between the patients and the controls (homozygous C/C genotype was overrepresented in patients, p = 0.008). Patients with osteoporosis were also three times more likely to carry the rs1544410 G/G genotype, when compared to controls. We found that rs7975232, rs1544410, and rs731236 variants were in a strong direct linkage disequilibrium (p < 0.0001), suggesting that risk alleles of these markers are preferably inherited jointly. For the bearers of C-G-C haplotype (consisting of rs7975232, rs1544410, and rs731236 unfavorable alleles), the risk of PMO was significantly higher (OR = 4.7, 95% CI 2.8–8.1, p < 0.0001) compared to controls. This haplotype was significantly over-represented in PMO group compared to all other haplotypes. Our findings highlight the importance of identified haplotypes of VDR gene variants. Complex screening of these genetic markers can be used to implement personalized clinical approach for prevention, treatment, and rehabilitation programs.

Comparative clinical study between lashuna and shatavari in minimizing the risk of postmenopausal osteoporosis

Ayurveda is one of the old traditional science which deals with healthy and diseased state of human beings through lifestyle, dietary supplements, medication, yoga, purification techniques. In decades of old age can be reduced by the rasayana therapy, which is the line of treatment for vriddha age groups with dominant of vata dosha, agni mandya, dhatu and upadhatu Kshaya. Women are mostly vulnerable at early stage by the vata dosha, dhatu Kshaya especially asthi dhatu, upadhatu like aartava etc. Kshaya of asthi dhatu in menopausal period can be considered as menopausal osteoporosis. Prevention is better than cure as per this proverb, this study was held to prevent the risk of postmenopausal osteoporosis with the drugs lashuna and shatavari treated in comparison method. By its guna of snigdha, vatahara, rasayana etc.

Associations between ER\u03b1/\u03b2 gene polymorphisms and osteoporosis susceptibility and bone mineral density in postmenopausal women: a systematic review and meta-analysis

BackgroundMany studies have reported associations between estrogen receptor (ER) gene polymorphisms and postmenopausal osteoporosis (PMOP) risk and bone mineral density (BMD), but the results are controversial. The aim of the present meta-analysis is to verify the association between ERα and ERβ gene polymorphisms and osteoporosis susceptibility and BMD in postmenopausal women.MethodsPubMed, EMBASE, Web of Science, the Cochrane Library and China WeiPu Library were searched. OR and WMD with 95% CI were calculated to assess the association.ResultsOverall, no significant association was observed between ERα XbaI, ERα PvuII and PMOP susceptibility in either overall, Caucasian or Asian populations. ERα G2014A was significantly associated with a decreased risk of PMOP in Caucasian populations. There was a significant association between ERβ RsaI and PMOP risk in both overall and Asian populations. Caucasian PMOP women with ERα XbaI XX and Xx genotypes had a higher LS Z value than women with xx genotype. ERα XbaI XX genotype was associated with increased FN BMD in overall and Caucasian populations, an increased FN Z value in Asians, and a decreased FN Z value in Caucasians. There was also a significant association between ERα XbaI Xx genotype and an increased FN Z value in either Asians or Caucasians. ERα PvuII PP genotype was associated with a low LS Z value in Caucasians and a low FN BMD and Z value in Asians. Pp genotype in PMOP women was significantly correlated with low LS BMD in overall populations, a low FN Z value in either overall, Caucasian or Asian populations.ConclusionEach ERα and ERβ gene polymorphism might have different impact on PMOP risk and BMD in various ethnicities.

RETRACTED ARTICLE: Associations between VDR Gene Polymorphisms and Osteoporosis Risk and Bone Mineral Density in Postmenopausal Women: A systematic review and Meta-Analysis

Results on the relationships between vitamin D receptor (VDR) gene polymorphisms and postmenopausal osteoporosis (PMOP) susceptibility and bone mineral density (BMD) are conflicting. The aim of the study is to identify more eligible studies that calculated pooled OR and WMD with 95% CI to assess their associations. Overall, there were significant correlations between VDR ApaI, VDR FokI and PMOP susceptibility. Subgroup analysis showed that VDR ApaI polymorphism significantly decreased the osteoporosis risk in Caucasian postmenopausal women. In Asian populations, VDR BsmI and VDR FokI were associated with an increased risk of PMOP. As to the associations between VDR polymorphisms and BMD, Caucasian PMOP women carrying the ApaI aa genotype were at risk of high BMD in femoral neck, and low femoral neck BMD was observed in Caucasian PMOP women with FokI Ff genotype. PMOP women with the Cdx2 GA genotype had a lower lumbar spine BMD in overall and Caucasian populations compared with PMOP women with GG genotype. Different VDR gene polymorphisms have different impacts on PMOP risk and BMD.

Fruit and vegetable consumption and the risk of postmenopausal osteoporosis: a meta-analysis of observational studies.

The association of the consumption of fruit and vegetables (FV) and the risk of postmenopausal osteoporosis (PMOP) has been a controversial subject. Thus, we carried out a meta-analysis to evaluate the association of FV consumption and the risk of PMOP. PubMed, Web of Science and Wan Fang were searched for relevant articles published up to March 2018. To evaluate the association of FV intake and PMOP risk, combined odds ratio (OR) and 95% confidence intervals (CIs) were calculated with the fixed or random effects model. Eighteen studies involving 12 643 participants were included in this meta-analysis. When comparing the highest with the lowest consumption, the pooled OR of PMOP was 0.68 (95% CI, 0.56-0.83; I2 = 57.3%; REM) for fruit and 0.87 (95% CI, 0.65-1.16; I2 = 68.9%; REM) for vegetables. For the intake of fruit and the risk of PMOP, subgroup analysis showed a significant association in case-control studies (OR, 0.52; 95% CI, 0.35-0.77; I2 = 3.1%; FEM) and cross-sectional studies (OR, 0.73; 95% CI, 0.59-0.89; I2 = 61.1%; REM). For the intake of vegetables and the risk of PMOP, subgroup analysis showed a significant association in case-control studies (OR, 0.62; 95% CI, 0.42-0.90; I2 = 0.0%; FEM) but not in cross-sectional studies (OR, 0.95; 95% CI, 0.69-1.29; I2 = 68.9%; REM). This meta-analysis indicates that fruit intake might be beneficial for the prevention of osteoporosis in postmenopausal women. The findings need to be confirmed by further investigations.

Identifying risk factors for bone mass transition states for postmenopausal osteoporosis

IntroductionThe conventional risk factors and traditional Chinese medicine (TCM) symptoms plays an important part in the development of postmenopausal osteoporosis (PMOP). The purpose of this study was to identify risk factors affecting bone mass transition states for PMOP based on conventional risk factors and potential TCM symptoms. MethodsA questionnaire survey and bone mineral density tests were conducted over a 3 year period from March 2009 to November 2011. Every subject was regularly contacted and interviewed annually. The characteristics of the population with different bone mass were categorized. Risk factors were selected through univariate and multivariate analysis using the Markov model. Likelihood ratio test was used to compare the fitting effect of different variables for the same data. ResultsA total of 1021 participants were followed up for three consecutive years. In the period of follow up, 80 women suffered the normal-osteopenia transition, 43 women suffered the osteopenia-osteoporosis transition. Duration of menopause, height loss, and TCM symptoms including soreness and weakness of waist and knees, hair loss and leg pains were conventional risk factors of transition states for PMOP (P<0.05). A fresh vegetable diet could reduce the risk of transition (P<0.05). The Markov model based on the conventional risk factors and TCM symptoms had a satisfactory degree of fit. ConclusionFor the population with a high risk of PMOP, long duration of menopause, height loss, fresh vegetables diet, and TCM symptoms such as soreness and weakness of waist and knees, hair loss and leg pains play important role in early warning. The Markov model could be used for identifying the risk factors for the three-phases of bone mass transition for PMOP.

Epidemiological features of Spanish postmenopausal women attended at outpatient gynaecology. Postmenopausal osteoporosis risk calculation based on FRAX

sites. However, the eGFR according to the MDRD formula was significantly correlated with age and baPWV, but not with BMD at the lumbar spine, femoral neck and total hip. Decreased renal function (eGFR 1500 cm/s) after adjusting for confounding variables. Conclusion: Postmenopausal women with decreased renal function are more likely to have a decreased BMD and a greater arterial stiffness.

The Transforming Growth Factor-β1 (TGF-β1) Gene Polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and Susceptibility to Postmenopausal Osteoporosis

The aim of the present study was to integrate all the eligible studies and investigate whether the transforming growth factor-β1 (TGF-β1) gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) are correlated with postmenopausal osteoporosis (PMOP) risk.PMOP is a common skeletal disease and several genetic factors play an important role in the development and progression of PMOP. Significant associations between TGF-β1 gene polymorphisms (TGF-β1 T869C and TGF-β1 T29C) and PMOP risk have been reported; however, some of these results are controversial.A systematic online search was performed using PubMed, EMBASE, Web of Science, and the Cochrane Library to identify case–control studies investigating the relationship between TGF-β1 T869C and TGF-β1 T29C polymorphisms and the susceptibility of PMOP. The pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated to assess the associations, and subgroup meta-analyses were performed according to the ethnicity of the study populations.Eight studies involving 1851 cases and 2247 controls met the inclusion criteria after assessment by 2 reviewers. Overall, there were significant associations between TGF-β1 T869C and TGF-β1 T29C polymorphisms and PMOP (TGF-β1 T869C—C vs T: OR = 1.18, 95% CI = 1.02–1.36, P = 0.030; CC vs TT: OR = 1.38, 95% CI = 1.01–1.88, P = 0.042; CC vs CT/TT: OR = 1.39, 95% CI = 1.09–1.76, P = 0.008; TGF-β1 T29C—CT vs TT: OR = 1.25, 95% CI = 1.02–1.53, P = 0.032; CT/CC vs TT: OR = 1.37, 95% CI = 1.02–1.84, P = 0.035). In the subgroup analysis of ethnicity, significant association was observed between TGF-β1 T869C polymorphism and PMOP risk in Asian population (C vs T: OR = 1.18, 95% CI = 1.01–1.38, P = 0.043; CC vs TT: OR = 1.41, 95% CI = 1.01–1.97, P = 0.047; CT/CC vs TT: OR = 1.31, 95% CI = 1.03–1.66, P = 0.026; CC vs CT/TT: OR = 1.35, 95% CI = 1.03–1.75, P = 0.028); however, there was no significant association between TGF-β1 T869C polymorphism and PMOP risk in Caucasian population. With regard to TGF-β1 T29C polymorphism, significant association was also observed in Asian population (CT vs TT: OR = 1.37, 95% CI = 1.07–1.75, P = 0.013; CT/CC vs TT: OR = 1.54, 95% CI = 1.16–2.05, P = 0.003), while there was no significant association in Caucasian population.The TGF-β1 T869C and TGF-β1 T29C polymorphisms may be involved in susceptibility to PMOP, particular in Asian patients.

Collagen Type I alpha1 (COL1A1) Gene Polymorphism and Bone Mineral Density in Postmenopausal Kazakh Women.

IntroductionSingle nucleotide polymorphism (SNP) at the collagen type I alpha 1 gene (COL1A1) rs1800012 has been widely studied and has shown an association with bone mineral density (BMD) and fractures. A minor allele TT of this SNP was found to be greatly overrepresented in individuals with fractures compared to controls, thus becoming a good predictor of increased fracture risk. The aim of this investigation was to evaluate potential association between COL1A1 gene polymorphism and osteoporosis in Kazakh postmenopausal women.MethodsThe study population included 103 postmenopausal women recruited from Pavlodar and Almaty clinics. BMD was measured using DEXA. Genomic DNA was extracted from peripheral venous blood of study participants with Wizard® Genomic DNA Purification Kit (Promega, USA). Detection of COL1A1 +1245G/T (Sp1) polymorphism was done by the TaqMan® SNP Genotyping Assay of real-time PCR.ResultsDensitometry results revealed 36 osteoporotic, 42 osteopenic, and 25 normal postmenopausal women. Data analysis of 1245G>T polymorphism in COL1A1 gene in the group of women with osteopenia and osteoporosis revealed deviation from Hardy-Weinberg equilibrium. The mutant TT genotype was prevalent compared to the heterozygous genotype GT in both groups. Distributions were 83% GG, 3% GT, and 14% TT in the group with osteopenia and 80% GG, 6% GT, and 14% TT in the group with osteoporosis. The distribution of genotypes frequency in the group of normal postmenopausal women was 76% GG, 16% GT, and 8% TT.ConclusionThese results suggest that TT genotype of COL1A1 +1245G/T (Sp1) polymorphism is associated with risk of postmenopausal osteoporosis in Kazakh women. Further studies involving a larger number of women are needed to clarify the relationship of this polymorphism with risk of osteoporosis.

Association Between Polymorphisms of VDR, COL1A1, and LCT Genes and Bone Mineral Density in Belarusian Women With Severe Postmenopausal Osteoporosis

BACKGROUND AND OBJECTIVE. Variation of osteoporosis in the population is the result of an interaction between the genotype and the environment, and the genetic causes of osteoporosis are being widely investigated. The aim of this study was to analyze the association between the polymorphisms of the vitamin D receptor (VDR), type I collagen (COL1A1), and lactase (LCT) genes and severe postmenopausal osteoporosis as well as bone mineral density (BMD). MATERIAL AND METHODS. A total of 54 women with severe postmenopausal osteoporosis and 77 controls (mean age, 58.3 years [SD, 6.2] and 56.7 years [SD, 7.42], respectively) were included into the study. The subjects were recruited at the City Center for Osteoporosis Prevention (Minsk, Belarus). Dual-energy x-ray absorptiometry was used to measure bone mineral density at the lumbar spine and the femoral neck. Severe osteoporosis was diagnosed in the women with the clinical diagnosis of postmenopausal osteoporosis and at least 1 fragility fracture. The control group included women without osteoporosis. Polymorphic sites in osteoporosis predisposition genes (ApaI, BsmI, TaqI, and Cdx2 of the VDR gene, G2046T of the COL1A1 gene, and T-13910C of the LCT gene) were determined using the polymerase chain reaction on the deoxyribonucleic acid isolated from dried bloodspots. RESULTS. The data showed that the ApaI and BsmI polymorphisms of the VDR gene and T- 13910C of the LCT gene were associated with severe postmenopausal osteoporosis in the analyzed Belarusian women (P<0.01). A statistically significant positive correlation between the VDR risk genotypes ApaI and TaqI and bone mineral density was found (P<0.05). CONCLUSIONS. The findings of this study suggest that at least the ApaI and BsmI polymorphisms of the VDR gene and T-13910C of the LCT gene are associated with the risk of postmenopausal osteoporosis in our sample of the Belarusian women.