绝经后妇女骨质疏松患者血清IGF-1、IGFBP-3与骨密度及骨代谢指标的关系

目的： 探讨胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）与绝经后妇女骨密度及骨代谢指标之间的关系。方法： 通过检测90例绝经后妇女骨质疏松患者及70例绝经后骨量正常的健康对照组血清IGF-1、IGFBP-3、骨钙素（BGP）、I型胶原异构C端肽（β-CTX）、雌激素（E₂）、降钙素（CT）、甲状旁腺激素（PTH）、钙（Ca）、磷（P）等指标，然后同用双能X线骨密度仪检测的两组研究对象的腰椎（L2-L4）侧位、左股骨颈骨密度进行比较。结果： 绝经后骨质疏松组妇女腰椎、股骨颈骨密度显著低于对照组（均P<0.01）；血清IGF-1、IGFBP-3、E₂、CT、BGP水平均低于对照组（均P<0.01）；血清β-CTX、PTH均高于对照组（均P<0.01），血清Ca、P两组之间无差异（均P>0.05）。骨质疏松组和对照组腰椎侧位、左股骨颈BMD均与IGF-1、IGFBP-3、E₂、BGP、CT水平呈正相关，与β-CTX、PTH水平呈负相关，而与血钙、血磷无明显关系。结论： IGF-1、IGFBP-3、E₂、BGP、CT、β-CTX、PTH血清水平与腰椎、左股骨质具有明显的相关性，通过检测上述指标可考虑作为筛查绝经后妇女是否容易患有骨质疏松症的一项有价值的生化参考指标。     

Association study of semaphorin 7a (sema7a) polymorphisms with bone mineral density and fracture risk in postmenopausal Korean women

Bone mineral density (BMD), the major factor determining bone strength, is closely related to osteoporotic fracture risk and is determined largely by multiple genetic factors. Semaphorin 7a (SEMA7A), a recently described member of the semaphorin family, has been shown to play a critical role in the activation of monocyte/macrophages that share progenitors with bone-resorbing osteoclasts and thus might contribute to osteoclast development. In the present study, we directly sequenced the SEMA7A gene in 24 Korean individuals, and identified 15 sequence variants. Five polymorphisms (+15667G>A, +15775C>G, +16285C>T, +19317C>T, +22331A>G) were selected and genotyped in postmenopausal Korean women (n=560) together with measurement of the areal BMD (g/cm²) of the anterior-posterior lumbar spine and the non-dominant proximal femur using dual-energy X-ray absorptiometry. We found that polymorphisms of the SEMA7A gene were associated with the BMD of the lumbar spine and femoral neck. SEMA7A+15775C>G and SEMA7A+22331A>G were associated with low BMD of the femoral neck (P=0.02) and lumbar spine (P=0.04) in a recessive model. SEMA7A-ht4 also showed an association with risk of vertebral fracture (OR=1.87–1.93, P=0.02–0.03). Our results suggest that variations in SEMA7A may play a role in decreased BMD and risk of vertebral fracture.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized usersJung-Min Koh and Bermseok Oh contributed equally to this work     

TNFRSF11B gene variants and bone mineral density in postmenopausal women in Malta

A number of polymorphisms in various genes have been identified and associated with bone mineral density (BMD) and with an increased risk of osteoporosis.

Objective

In this study, three single nucleotide polymorphisms (SNPs) within the TNFRSF11B gene were studied for association with an increased risk of osteoporosis in postmenopausal Maltese women (n = 126).

Methodology

Analysis was performed by PCR restriction fragment length polymorphism (RFLP) while BMD at the lumbar spine, femoral neck, Ward's triangle and trochanter was measured by DEXA.

Results

No significant association was observed between genotypes and BMD for all polymorphisms studied within this gene. Homozygotes CC (T⁹⁵⁰–C) were observed to have the highest BMD at all anatomical sites although statistical significance was not reached when comparing the three genotypes. A statistical significant difference was observed in the distribution of genotype frequencies for this polymorphism between normal individuals and those that were either osteopenic or osteoporotic at one or both anatomical sites, with the TT genotype associated more frequently with low BMD. The T⁹⁵⁰–C and G¹¹⁸¹–C polymorphisms were in strong linkage disequilibrium with each other but not with the A¹⁶³–G polymorphism further upstream in the OPG promoter. Statistical significance was reached when constructing haplotypes, where the A–T–G haplotype was found to be more frequent in individuals with low BMD.

Conclusions

These results indicate the possible role of TNFRSF11B gene variants in postmenopausal bone loss in women in Malta.     

Evaluation of eNOS gene polymorphisms in relation to BMD in postmenopausal women

Objective

The aim of the present study was to evaluate the relations between T⁻⁷⁸⁶C and Glu298Asp polymorphisms of the endothelial nitric oxide synthase (eNOS) gene and BMD in postmenopausal Turkish women.

Methods

The T⁻⁷⁸⁶C and Glu298Asp polymorphisms were genotyped by PCR-RFLP method in 311 postmenopausal osteoporotic women (OP) and in 305 age-matched postmenopausal females (CG) with normal BMD.

Results

None of the SNPs of the eNOS gene was significantly associated with BMD at the lumbar spine, femoral neck, Ward's triangle and femoral trochanter in the combined group. Mean BMD values were therefore found to be similar across the genotypes in postmenopausal Turkish women. However, there was a significant association between the T⁻⁷⁸⁶C polymorphism and BMD values at the lumbar spine in the normal control group (P = 0.005), and at the femoral trochanter in the osteoporotic patients (P = 0.046). The mean value of the lumbar spine BMD in the normal controls was significantly higher in women with the TC genotype of the T⁻⁷⁸⁶C polymorphism than in women with the TT genotype (P = 0.0012). Women with the CC genotype of the T⁻⁷⁸⁶C polymorphism in the osteoporotic patients had significantly higher BMD value at the femoral trochanter than those with the TC (P = 0.018) and TT genotypes (P = 0.024). Frequencies of the TC heterozygotes for T⁻⁷⁸⁶C polymorphism were significantly higher among osteoporotic subjects than normal controls. Also, the CC and TT genotype frequencies of control group were significantly higher than those of the osteoporotic group at the femoral neck.

Conclusions

We conclude that, although the biological role of the nitric oxide synthases is well established, our study does not suggest that eNOS gene polymorphisms, T⁻⁷⁸⁶C and Glu298Asp, are major contributors to adult bone mineral density in the postmenopausal Turkish women.     

Cortical bone loss at the tibia in postmenopausal women with osteoporosis is associated with incident non-vertebral fractures: Results of a randomized controlled ancillary study of HORIZON

Background

In postmenopausal women, yearly intravenous zoledronate (ZOL) compared to placebo (PLB) significantly increased bone mineral density (BMD) at lumbar spine (LS), femoral neck (FN), and total hip (TH) and decreased fracture risk. The effects of ZOL on BMD at the tibial epiphysis (T-EPI) and diaphysis (T-DIA) are unknown.

Methods

A randomized controlled ancillary study of the HORIZON trial was conducted at the Department of Osteoporosis of the University Hospital of Berne, Switzerland. Women with ≥1 follow-up DXA measurement who had received ≥1 dose of either ZOL (n = 55) or PLB (n = 55) were included. BMD was measured at LS, FN, TH, T-EPI, and T-DIA at baseline, 6, 12, 24, and 36 months. Morphometric vertebral fractures were assessed. Incident clinical fractures were recorded as adverse events.

Results

Baseline characteristics were comparable with those in HORIZON and between groups. After 36 months, BMD was significantly higher in women treated with ZOL vs. PLB at LS, FN, TH, and T-EPI (+7.6%, +3.7%, +5.6%, and +5.5%, respectively, p < 0.01 for all) but not T-DIA (+1.1%). The number of patients with ≥1 incident non-vertebral or morphometric fracture did not differ between groups (9 ZOL/11 PLB). Mean changes in BMD did not differ between groups with and without incident fracture, except that women with an incident non-vertebral fracture had significantly higher bone loss at predominantly cortical T-DIA (p = 0.005).

Conclusion

ZOL was significantly superior to PLB at T-EPI but not at T-DIA. Women with an incident non-vertebral fracture experienced bone loss at T-DIA.     

Efficacy of ipriflavone in the prevention and treatment of postmenopausal osteoporosis

The efficacy of ipriflavone was investigated in a 1-year double-blind, placebo-controlled, parallel group clinical trial. Ninety-one postmenopausal women completed the study, 41 received ipriflavone and 50 placebo treatment. After six months the bone mineral density of the L2–L4 vertebral region increased in the ipriflavone-treated group (0.015 g/cm²), whereas it decreased in the placebo-treated group. The differences between the treatment groups were statistically significant. Our results support the efficacy of ipriflavone in the treatment of postmenopausal osteoporosis. Since the positive effect was more pronounced after 6 months, the possibility of an intermittent ipriflavone treatment might be taken into consideration in the future.     

Safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density: a meta-analysis

Purpose: The aim of this meta-analysis was to assess the safety of denosumab in postmenopausal women with osteoporosis or low bone mineral density (BMD). Methods: Safety of denosumab was compared with placebo or bisphosphonates. A systematic literature search without language restriction was conducted up to January, 2014. The RevMan 5.1 software was used for statistical analysis. Results: A total of 11 English literatures were eventually identified. The pooled data in the overall analysis revealed that there was no significant difference when compared denosumab with placebo or bisphosphonates in any adverse events (AAE) (RR=0.99, 95% CI=0.98-1.01, p=0.29), serious adverse event (SAE) (RR=1.05, 95% CI=0.98-1.13, p=0.18), neoplasm/cancer (RR=1.14, 95% CI=0.95-1.37, p=0.16) and deaths (RR=0.77, 95% CI=0.57-1.04, p=0.09). However, significant differences were found when compared denosumab with placebo or bisphosphonates in SAE related to infection (RR=1.23, 95% CI=1.00-1.52, p=0.05) and non-vertebral fracture (RR=0.86, 95% CI=0.74-1.00, p=0.05). Subgroup analysis was performed by the type of drugs which was used in the control group. The results of subgroup analysis did not demonstrate the differences between denosumab and bisphosphonates in SAE related to infection (RR=1.13, 95% CI=0.63-2.03) and non-vertebral fracture (RR=1.31, 95% CI=0.87-1.98). Conclusions: Compared to placebo, denosumab treatment significantly decreased the risk of non-vertebral fracture but increased the risk of SAE related to infection in the postmenopausal women with osteoporosis or low BMD. However, no difference between the safety of denosumab and bisphosphonates was found.     

绝经后妇女甲状旁腺素基因多态性与骨密度：福州地区的调查

背景：有研究证实,绝经后妇女骨密度与甲状旁腺素基因有密切关系,但在不同地区人群中结果存在差异性。 目的：探讨福州地区绝经后妇女甲状旁腺素基因(PTH)BstBⅠ多态性与骨密度的关系。 方法：用双能X射线骨密度仪检测福州地区150例绝经后妇女的腰椎、股骨颈,大转子和Ward’s三角骨密度,应用PCR-RFLP技术检测甲状旁腺素基因BstBⅠ多态性。 结果与结论：①甲状旁腺素基因型分布频率为BB型 68.8%、Bb型24.1%、bb 型7.1%。等位基因频率为B 81%,b 19%,基因型分布符合Hardy-Weinberg定律。②分析其基因型与骨密度的关系：BB、Bb、bb 3种基因型在股骨颈、大转子、Ward’s三角区4个部位骨密度差异均无显著意义(P > 0.05)。甲状旁腺素基因BstBⅠ位点多态性与骨密度间无关联,尚不能作为预测福州地区绝经后妇女发生骨质疏松危险的遗传标志。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Association of KIT gene polymorphisms with bone mineral density in postmenopausal Korean women

Bone mineral density (BMD) is a major factor for determining bone strength and osteoporotic fracture risk, and is determined by environmental and multiple genetic factors. KIT, which encodes a transmembrane receptor with tyrosine kinase activity, plays an important role in the differentiation of osteoclasts. We examined the associations between KIT gene polymorphisms and BMD in postmenopausal Korean women. All exons, their boundaries, and the promoter region (approximately 1.5 kb) from 24 individuals were directly sequenced. Eighteen polymorphisms were identified, and three single-nucleotide polymorphisms (SNPs) were genotyped in all study participants (n = 946). BMD at the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry. The mean age of the study subjects was 58.9 ± 7.5 years, and the mean number of years since menopause was 9.6 ± 7.9 years. None of the three SNPs (−1694G>T, +41894A>G, and +49512G>A) was significantly associated with BMD value. However, multivariate analysis showed that the ht3 (−1694T-+41894A-+49512G) was significantly associated with lower BMD at the femoral neck (P = 0.007 in the recessive model). These findings indicate that KIT-ht3 may be a useful genetic marker for osteoporosis and that KIT may have a role on bone metabolism in humans. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. S.-Y. Kim and J.-Y. Lee are co-first authors.     

TNFRSF11B gene haplotype and its association with bone mineral density variations in postmenopausal Mexican-Mestizo women

Objective

Osteoporosis is a complex health disease characterized by low bone mineral density (BMD), which is determined by an interaction of genetics with metabolic and environmental factors. The tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) gene, has been investigated in relation to BMD. Three polymorphisms in/nearby TNFRSF11B have been associated with BMD variations in some populations. The aim of this study was to investigate the possible association among three SNPs of TNFRSF11B and their haplotypes with the presence of BMD variations in postmenopausal Mexican Mestizo women.

Subjects and methods

One thousand unrelated postmenopausal women of Mexican-Mestizo ethnic origin, who attended the outpatient clinic for routine, general medical evaluation, were invited and 750 women accepted to participate in the study. A structured questionnaire for risk factors was applied and BMD was measured in total hip and lumbar spine by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Three single-nucleotide polymorphisms in TNFRSF11B gene were studied: rs4355801, rs2073618, and rs6993813. Real-time PCR allelic discrimination was used for genotyping. Deviations from Hardy–Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r², and haplotype analysis was conducted.

Results

Of the subjects, 31% had osteoporosis, 45.1% had osteopenia, and 23.9% had normal BMD. Genotype and allele distributions showed no significant differences; however, A–G–T haplotype was associated with variations in femoral neck BMD (P = 0.022).

Conclusions

In our study population, analysis of the haplotypes of TNFRSF11B is a better genetic marker for variations in BMD.     

骨保护素基因G1181C多态性与绝经妇女骨密度的Meta分析

背景：遗传学研究显示骨保护素基因G1181C多态性与绝经妇女骨密度可能存在关系,但研究结论存在一定差异。 目的：采用Meta分析方法研究骨保护素基因G1181C(rs2073618)多态性与绝经后妇女骨密度的关系。 方法：检索PubMed、Embase、CNKI、万方数据库中关于骨保护素基因rs2073618位点G1181C多态性与骨密度关系的观察性研究。以标准化均数差为效应指标,并根据异质性检验结果选择随机效应模型或固定效应模型计算标准化均数差。 结果与结论：纳入9篇文献,测定椎骨骨密度8 799人,测定股骨颈骨密度9 365人。分析结果显示,携带G等位基因的绝经妇女椎体骨密度比携带C等位基因者低,高加索人群亚组分析显示相同结果。此外,高加索人群的亚组分析显示,携带GG基因型的绝经妇女股骨颈骨密度低于携带GC和CC基因型者。说明骨保护素基因G1181C多态性与绝经后妇女骨密度存在相关性,G等位基因是发生骨密度降低的危险因子。     

骨代谢相关基因多态性与盐酸雷洛昔芬对绝经后骨质疏松妇女骨密度和骨转换指标影响的关系

目的了解骨代谢相关基因多态性与盐酸雷洛昔芬( raloxifene,RLX)对绝经后骨质疏松妇女骨密度(bone mineral density, BMD)和骨转换指标影响的关系.方法为随机、对照和双盲试验,入选47～74岁68例无亲缘关系的绝经后骨质疏松汉族妇女,随机分为RLX组和安慰剂组(各34例),RLX组日服RLX 60 mg,安慰剂组服与RLX外观一致的安慰剂,共1年.在服药前、服药后6月和12月时,检测BMD和骨转换指标包括血清1型胶原羧基末端肽(C-telopeptide, CTX)和骨钙素(osteocalcin, BGP).分析雌激素受体1基因(estrogen receptor 1 gene,ESR1)Xba Ⅰ和PvuⅡ位点、ESR2基因RasⅠ位点、维生素D受体基因(vitamin D receptor, VDR)FokⅠ和CDX2结合位点的多态性. 结果共58例完成整个试验,研究结束时RLX组腰椎2～4(L2～4)、全髋部和大转子BMD增加的百分数,以及血清CTX和BGP水平下降的百分数与安慰剂组比较差异均有统计学意义(P<0.05或P<0.01).治疗后12个月,RLX组VDR FokⅠ FF基因型者(n=8)全髋部和大转子BMD值平均下降各为1.98%±4.86%和2.26%±4.73%,而Ff/ff基因型者(n=21)平均增加各为2.52%±2.75%和2.74%±2.97%(P<0.05);ESR1 PvuⅡ位点PP/Pp基因型者(n=17)全髋部BMD明显增加(2.12%±2.78%),而pp基因型者(n=12)呈下降(-1.34%±3.73%)(P<0.05).但上述5个位点多态性与安慰剂组各指标变化均无相关性. 结论 RLX对绝经后骨质疏松妇女BMD的作用受VDR基因FokⅠ和ESR1基因PvuⅡ多态性的调节.在临床选择该药物时,可根据应用对象的基因型做有益决策之用.     

骨密度影像学测量与椎体骨折率评估结合提高骨质疏松的诊断率

背景：临床上用于诊断骨质疏松症的通用指标：脆性骨折或骨密度T ≤ -2.5标准差,只要满足一个条件即可作出骨质疏松的诊断。在做骨密度检查时同时进行椎体骨折评估,可以避免单一因素的评判造成骨质疏松症的漏诊,有利于提高骨质疏松的诊断率。 目的：评估骨密度结合椎体骨折对骨质疏松症临床诊断率的影响。 方法：对217例年龄≥50岁的绝经后女性患者行髋部骨密度检测,同时进行椎体骨折评估,比较单纯依靠骨密度检查与骨密度结合椎体骨折评估对骨质疏松的诊断率的影响,同时探讨骨密度对椎体骨折率的影响。 结果与结论：92例骨密度T ≤ -2.5,达到骨质疏松诊断阈值,占42.4%;102例骨密度-1 > T > -2.5,为低骨量,占47.0%;23例骨密度在正常范围,骨密度T > -1,占10.6%。158例无椎体骨折;59例(27.2%)椎体骨折,101个骨折椎。骨密度T > -2.5的患者椎体骨折率为21.6%,骨密度T ≤ -2.5的患者椎体骨折率34.8%,两组骨折率比较差异有显著性意义(P < 0.05);骨密度结合椎体骨折评估的骨质疏松诊断率为54.8%,比单纯依靠骨密度检查,骨质疏松诊断率提高12.4%(P=0.01)。说明绝经后女性做骨密度检测的同时进行椎体骨折评估可以提高骨质疏松的诊断率。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

抗阻训练干预绝经后骨质疏松患者骨密度的系统综述和Meta分析

背景:抗阻训练已经被证实对于改善绝经后妇女骨质疏松患者的骨密度有所帮助,但抗阻运动的运动方式、训练强度、训练时间、训练频率,以及与不同运动(有氧运动等)方式的结合是否效果更好还有待研究。目的:评价抗阻训练对绝经后妇女骨质疏松患者骨密度的干预效果。方法:搜集抗阻训练干预绝经后妇女骨质疏松患者骨密度的相关随机对照试验,研究对象分为抗阻训练组及空白对照组,检索Pub Med、EMBASE、Web of Science、中国知网和万方医学数据库,检索的时间范围从建库到2019年12月,并且对纳入文献的相关参考文献进行检索。由2名研究者按纳入和排除标准筛选文献并提取有效数据,进行质量评价。采用Rev Man 5.3软件对最终纳入的文献数据进行Meta分析。结果与结论:①最终纳入23篇随机对照试验,对纳入的文献进行风险偏倚评价,结果显示整体文献质量为中等偏上;②Meta分析结果显示,与空白对照组相比,抗阻训练组可显著改善绝经后妇女骨质疏松患者的腰椎骨密度[SMD=0.02,95%CI(0.01,0.03),P<0.0001]、全髋骨密度[SMD=0.25,95%CI(0.06,0.44),P=0.03]、股骨颈骨密度[SMD=0.28,95%CI(0.12,0.04),P=0.0005]及大转子骨密度[SMD=0.02,95%CI(0.00,0.03),P=0.02];③提示抗阻训练有利于维持绝经后妇女骨质疏松患者的骨密度水平,可以作为绝经后妇女骨质疏松运动治疗的重要组成部分。     

Association of TNFSF11 gene promoter polymorphisms with bone mineral density in postmenopausal women

OBJECTIVES: The receptor activator of nuclear factor-kappaB ligand (RANKL) is recognized as one of the important regulators of osteoclastogenesis. The expression of the tumour necrosis factor superfamily, member 11 (TNFSF11) gene, which encodes for RANKL protein, is increased relative to the expression of osteoprotegrin in cases of senile osteoporosis with hip bone fracture. Our aim was to find polymorphisms in the TNFSF11 gene promoter and to investigate their possible association with bone mineral density (BMD). METHODS: The TNFSF11 gene promoter region was screened for the presence of new sequence variations by direct sequencing. DNA sequencing revealed the presence of four sequence variations: -290C>T, -643C>T, -693G>C and -1594G>A. Association of the discovered polymorphisms with BMD was investigated in 115 Slovenian postmenopausal women, using restriction fragment length polymorphism analysis. After a year, bone loss in the association with the identified sequence variations was evaluated in 43 postmenopausal women. RESULTS: Three of the discovered sequence variations (-290C>T, -643C>T, -693G>C) proved to be polymorphic, whereas variation -1594G>A was only found in one patient. The frequencies of genotypes were as follows: CC (27.8%), CT (43.5%), TT (28.7%) for -290C>T polymorphism; CC (23.5%), CT (47.8%), TT (28.7%) for -643C>T polymorphism; and GG (22.6%), GC (51.3%), CC (26.1%) for -693G>C polymorphism. A statistically significant association of genotype with BMD at the femoral neck was observed only in the -290C>T polymorphism. Genotype CC was associated with lower BMD than the TT genotype (P = 0.022). In polymorphism -693G>C, a significant difference in bone loss rate was observed in total hip (P = 0.011) and femoral neck BMD (P = 0.037). CONCLUSIONS: Four sequence variations were identified in the studied region of TNFSF11 gene promoter. Our results of preliminary clinical evaluation suggest that the -290C>T polymorphism in the TNFSF11 gene promoter could contribute to the genetic regulation of BMD.     

The vitamin D receptor FokI start codon polymorphism and bone mineral density in osteoporotic postmenopausal French women

This study examined the association between bone mineral density (BMD) and a T/C polymorphism in the first of the two initiation codons in the vitamin D receptor (VDR) gene. The polymorphism was detected using the restriction enzyme FokI, the F allele indicating absence of the first codon and the f allele its presence. The FokI genotype was determined in 124 postmenopausal osteoporotic French women who were 45-90 years old. The distribution of FokI genotypes in the osteoporotics did not differ significantly from that found in a control group. There were no significant differences by FokI genotype groups in our total sample of osteoporotic women for age, years since menopause, height, weight, and BMD at lumbar spine and femoral neck. However, when only those patients under the age of 75 years are analysed (98 subjects), those with the ff genotype (10% of the population) had a significantly lower BMD at the femoral neck than FF and Ff subjects. This suggests that the ff genotype of the VDR gene correlates with decreased BMD at the femoral neck in French postmenopausal women.     

妊娠期糖尿病患者肿瘤坏死因子-α基因多态性的实验性研究

目的研究东北汉族妊娠期糖尿病(GDM)孕妇肿瘤坏死因子-α(TNF-α)基因多态性的分布频率及在GDM发病中的作用.方法选取120例GDM作为病例组,120例糖耐量正常的孕妇作为对照组,采用双抗体夹心酶联免疫吸附试验(ELISA)检测血清TNF-α水平,以稳态模型Homa model公式评估胰岛素抵抗(IR),同时应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,检测TNF-α基因-308和-238位点等位基因和基因型的分布频率.结果⑴ GDM组及对照组的血清TNF-α水平分别为(10.29±2.44) μg/L 和(5.21±1.01) μg/L (P＜0.05);FINS分别为(24.34±12.84 ) mIU/L 和(17.88±7.31 ) mIU/L(P＜0.01);HOMA-IR分别为(2.74±1.06) 和(1.35±0.69) (P＜0.01).⑵GDM组-238多态性位点A等位基因频率(0.0583和0.0417)及GA AA基因型频率(0.1083和0.0917)均高于正常妊娠对照组,但差异无统计学意义(P＞0.05).GDM组-308多态性位点A等位基因频率(0.1375和0.0583)及GA AA基因型频率(0.2417和0.1167)显著高于正常妊娠对照组,差异有统计学意义(P＜0.05).⑶GDM组GA AA基因组及GG基因型组TNF-α分别为[(6.35±1.43) μg/L]和[(5.68±0.45) μg/L] (P＜0.05);FINS分别为(13.42±4.73) mIU/L和(10.40±3.63) mIU/L(P＜0.01);HOMA-IR分别为(7.42±1.93)和(4.11±1.31)(P＜0.01).结论我国东北汉族孕妇人群中,TNF-α基因 308G→A变异可增加孕妇患妊娠期糖尿病的危险性.A等位基因可能通过增加TNF-α的释放参与胰岛素抵抗,导致GDM的发病.     

A susceptible haplotype within APOE gene influences BMD and intensifies the osteoporosis risk in postmenopausal women of Northwest India

Background

The association of apolipoprotein E (APOE) genotypes with bone mineral density (BMD) and risk of osteoporosis have remained unclear. The influence of APOE gene polymorphisms on BMD as genetic mediators of osteoporosis risk needs to be explored in Indian postmenopausal females where this disease is rising rampantly.

Methods and results

The present study investigated the role and relevance of four pertinent APOE single nucleotide polymorphisms: 5′UTR G/C (rs440446), Int2 G/A (rs769450), Exon4 T/C (rs429358), Exon4 C/T (rs7412) in DEXA verified 133 osteoporotic, 57 osteopenic and 83 normal postmenopausal females of India, who were not taking hormone replacement therapy. Minor allele frequencies of rs440446 and rs429358 were higher in osteoporotic females (0.31, 0.18) than osteopenic (0.29, 0.15) and females having normal bone mass (0.16, 0.07). Disease association analysis revealed a susceptibility haplotype CGTC (in order of rs440446, rs769450, rs429358, rs7412) and the carriers of this haplotype has higher risk of osteopenia (OR 3.53, 95% CI 1.21–11.0, P = 0.017) and osteoporosis (OR 3.61, 95% CI 1.53–9.48, P = 0.002) after adjusting the confounding effect of age, BMI and years since menopause. Females who possess either one copy or two copies of the haplotype have lesser BMD values of lumbar spine (0.88 and 0.85 g/cm²) and femoral neck (0.84 and 0.82 g/cm²) than those females who possess zero copy (0.9 and 0.87 g/cm², respectively).

Conclusions

The present study exposed a susceptibility haplotype CGTC, within APOE gene, which was found to be associated with BMD and risk of osteopenia and osteoporosis in postmenopausal females of India.     

Circulating vascular endothelial growth factor concentrations in patients with postmenopausal osteoporosis

Introduction

The role of vascular endothelial growth factor (VEGF) in osteoporosis has not yet been clearly established. Vascular endothelial growth factor is an important part of bone formation. In the literature, although the effects of VEGF on bone metabolism were investigated by different studies, there are very rare studies analysing the association between osteoporosis and VEGF. In the present study, our objective was to investigate serum VEGF concentrations in patients with postmenopausal osteoporosis (PMO) and the correlation of serum VEGF levels and bone mineral density (BMD).

Material and methods

This study was performed on 35 PMO patients, and 30 age-matched healthy controls. Serum VEGF concentrations were measured using a quantitative sandwich enzyme immunoassay technique according to the manufacturer''s instructions. Bone mineral density values were determined by dual energy X-ray absorptiometry (DEXA).

Results

Serum VEGF concentrations were statistically significantly lower in PMO patients than in controls (150 ±65 pg/ml, 260 ±135 pg/ml respectively; p = 0.005). A positive correlation was found between serum VEGF concentrations and BMD values (r = 0.63, p = 0.001).

Conclusions

Vascular endothelial growth factor concentrations were decreased in PMO patients and VEGF may play an important role in bone health.     

Relationship between postmenopausal osteoporosis and the components of clinical sarcopenia

Purpose

The aim of the study was to determine the relationship between the components of clinical sarcopenia and osteoporosis in postmenopausal women.

Methods

A population-based cohort of 590 Finnish postmenopausal women (mean age 67.9; range 65–72) was selected from the Osteoporosis Fracture Prevention (OSTPRE-FPS) study in 2002. Bone mineral density (BMD) and lean tissue mass were assessed by dual X-ray absorptiometry (DXA). The study sample was divided into three categories according to the WHO BMD classification: normal, osteopenia and osteoporosis. The study sample was divided into non-sarcopenic, presarcopenic, sarcopenic and non-classified groups according to quartiles of RSMI i.e. relative skeletal muscle index (appendicular muscle mass (kg)/square of height (m)), hand grip strength (kPa) and walking speed.

Results

In logistic regression analysis sarcopenic women had 12.9 times higher odds of having osteoporosis (p ≤ 0.001, OR = 12.9; 95% CI = 3.1–53.5) in comparison to non-sarcopenic women. In comparison to women in the highest grip strength quartile, women within the lowest quartile had 11.7 times higher odds of having osteoporosis (p = 0.001, OR = 11.7; 2.6–53.4). Sarcopenic women had 2.7 times higher odds of having fractures than their non-sarcopenic counterparts (p = 0.005, OR = 2.732; 1.4–5.5). Sarcopenic women had also 2.1 times higher risk of falls during the preceding 12 months compared to non-sarcopenic women (p = 0.021, OR = 2.1; 1.1–3.9). Adjustment for age, body mass index (BMI), physical activity and hormone therapy (HT) did not significantly alter these results.

Conclusions

The components of clinical sarcopenia are strongly associated with osteoporosis. Grip strength is the most significant measurement to reveal the association between sarcopenia and osteoporosis, falls and fractures.