HLA alleles as predisposal factors for postmenopausal osteoporosis in a Greek population

It is well established that genetic factors play an important role in the pathogenesis of osteoporosis, a common condition characterized by reduced bone mass and increased fracture risk. The major histocompatibility complex in humans, known as human leukocyte antigen (HLA) region, is the most polymorphic human genetic system and it is known as a cluster of genetic markers, associated with several diseases. In order to evaluate the contribution of HLA alleles in bone mass loss, polymorphisms in the HLA class I (-A, -B and -Cw) and class II (-DR and -DQ) antigens were studied in 126 postmenopausal women of Greek origin. It was found that HLA-B7 (P= 0.069), -DR15 (P= 0.019) and -DQ6 (P= 0.026) were associated with a lower bone mineral density measured at the forearm. This study shows a significant association between HLA alleles and bone mass loss in the population studied.     

Transient regional osteoporosis

Transient regional osteoporosis (TRO) is a disease that predisposes to fragility fracture in weight bearing joints of mid-life women and men. Pregnant women may also suffer the process, usually at the hip. The prevalence of TRO is lower than the systemic form, associated with postmenopause and advanced age, but may be falsely diminished by under-diagnosis. The disease may be uni- or bilateral, and may migrate to distinct joints. One main feature of TRO is spontaneous recovery. Pain and progressive limitation in the functionality of the affected joint(s) are key symptoms. In the case of the form associated with pregnancy, difficulties in diagnosis derive from the relatively young age at presentation and from the clinical overlapping with the frequent aches during gestation. Densitometric osteoporosis in the affected region is not always present, but bone marrow edema, with or without joint effusion, is detected by magnetic resonance. There are not treatment guidelines, but the association of antiresorptives to symptomatic treatment seems to be beneficial. Surgery or other orthopedic interventions can be required for specific indications, like hip fracture, intra-medullary decompression, or other.     

异黄酮与骨质疏松

异黄酮是一类植物雌激素,因具有和雌激素相似的化学结构,能与雌激素受体结合发挥抗骨质疏松的作用,而无明显的雌激素对乳腺和子宫内膜的副作用,从而提供了治疗绝经后骨质疏松的新途径。临床调查归纳近来异黄酮临床试验不同的结果,动物实验和基础研究进一步阐明异黄酮最重要两个单体———染料木素和大豆苷元抗骨质疏松的机制。     

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.     

淫羊藿水提液对去势大鼠松质骨的影响

目的：观察灌服淫羊藿水提液后的去势大鼠松质骨改变，探讨淫羊藿在防治绝经后骨质疏松症中的价值。方法：采用3月龄SD雌性大鼠30只，随机分为正常对照组（1组）、去势组（2组）和实验组（3组）。2组及3组均切除双侧卵巢，3组给予淫羊藿水提液灌胃处理；1组给予假手术处理。分别于术后4、12周，随机处死3组大鼠中各5只，取第5腰椎，脱钙后包埋切片。切片分别作HE及Van Gieson染色：图像分析骨小梁结构并计数多核巨噬细胞／破骨样细胞。结果：去势组与正常对照组比较，4周时出现骨小梁厚度下降，12周时骨小梁面积百分比下降明显，骨小梁分离度增加。实验组在骨小梁计量上与对照组相似，与去势组比较具有显著差异。去势组多核巨噬细胞／破骨样细胞计数多于正常对照组及实验组，有显著意义。结论：淫羊藿水提液通过抑制去势后大鼠松质骨基质中破骨细胞的生成，阻止了由于雌激素缺失引起的骨丢失，能有效预防骨质疏松症的发生。     

Mineral alterations in senile osteoporosis

This research investigates the occurrence of involutional processes of mineral transformation in elderly patients with clinical, radiographie and histological signs of senile osteoporosis. The decreased ability to withstand static and dynamic stresses proved to be associated either with the quantitative reduction in trabeculae or with the altered morphology of hydroxyapatite (HA) crystals. This variation produces a non-homogeneous mineral distribution which leads to a substantial alteration of the system of the stress lines producing mechanical bone behaviour. This altered distribution in mineral density has been attributed to the dynamic loss of balance between osteoblastic and osteoclastic activity; this is believed to be a peculiarity of senile osteoporosis.     

Post-menopausal women and osteoporosis: available choices for maintenance of skeletal health

Objective: To briefly summarize the therapeutic choices for osteoporosis prevention which are currently available to post-menopausal women. Methods: Results of randomized clinical trials and epidemiological studies in post-menopausal women, and pre-clinical studies in ovariectomized rats were summarized. Results: Estrogen combined with progestogen in hormone replacement therapy (HRT) is effective in relieving perimenopausal symptoms and maintaining bone mineral density. However, the increased breast cancer risk associated with long-term HRT use makes it a less desirable option for many women. Selective estrogen receptor modulators (SERMs), such as raloxifene, are also effective in maintaining bone density, without stimulating the breast or uterus. However, SERMs do not relieve perimenopausal hot flashes. Conclusion: HRT is effective for acute relief of perimenopausal symptoms, but for women who are unwilling or unable to take HRT long-term, SERMs such as raloxifene are a useful therapy for the prevention of osteoporosis.     

Mitochondria-wide association study of common variants in osteoporosis

Mitochondrial DNA (mtDNA) variants are involved in the pathogenesis of human complex diseases, especially for age-related disorders, including osteoporosis. However, the role of mtDNA variants in osteoporosis is largely unknown. In this study, we performed a mitochondria-wide association study for osteoporosis in a large sample of 2286 unrelated Caucasian subjects. A total of 445 mtSNPs were genotyped and 72 mtSNPs survived the quality control. We first examined association between mtSNPs and bone mineral density (BMD), and identified that an mtSNP, mt4823 within the ND2 gene, was strongly associated with hip BMD (P= 2.05 × 10(-4)), even after Bonferroni correction. The C allele of mt4823 was associated with reduced hip BMD and the effect size (β) was ～0.044. Another SNP mt15885 within the MT-CYB gene was associated both with spine (P= 1.66 × 10(-3)) and hip BMD (P= 0.023). The T allele of mt15885 had a protective effect on spine (β= 0.064) and hip BMD (β= 0.038). Next, we classified subjects into the nine common European haplogroups and conducted association analyses. Subjects classified as haplogroup X had significantly lower hip BMD values than others (P= 0.040). Our results highlighted the importance of mtDNA variants in osteoporosis.     

骨质疏松症的遗传学研究进展及对相关问题的思考

近10多年来,骨质疏松症的遗传学研究取得长足进展。研究发现多种与骨代谢密切相关的内分泌激素、骨基质蛋白、细胞因子遗传学变异与骨密度、骨质量、骨结构、骨转换率和骨质疏松性骨折率密切相关,本文旨在回顾国内外骨质疏松症遗传学领域重要的代表性研究成果,并思考骨质疏松遗传学研究今后需要关注的问题。     

骨质疏松症治疗中的运动疗法

背景：骨质疏松症是以骨量减少、骨组织显微结构退化为特征,以致骨的脆性增高而骨折危险性增加的一种全身骨病,通常治疗的首要手段为药物治疗。而单纯药物治疗无法提高肌肉力量,改善平衡功能,进而预防跌倒的发生,因此已不能满足骨质疏松症的综合管理。运动作为一种重要的非药物治疗手段,在骨质疏松症的预防中公认应作为首选,在骨质疏松症的治疗中的重要性逐渐被认识。 目的：结合最新的一些研究文献,探讨运动在骨质疏松症治疗中的作用。 方法：以“骨质疏松症,骨密度,骨强度,治疗,运动,应力,太极,肌肉,骨组织构建”为中文检索词,以“osteoporosis,bone mineral density, bone strength, treatment,exercise,stress,tai chi,muscle,bone architecture”为英文检索词,检索中国知网(CNKI)期刊全文数据库和Medline 2001年1月至2013年2月有关不同运动类型对人骨强度的影响特别是对骨质疏松症患者的治疗作用的临床报道及机制研究。排除重复性研究和不典型报道。 结果与结论：治疗性运动包括有氧运动、抗阻运动、冲击性运动、振动运动等类型,可以安全的提高骨强度,提高肌肉力量,改善平衡功能,预防跌倒和骨折。对于脊柱畸形者适当选用矫形器可提高安全性、促进运动治疗。与药物治疗一样,运动治疗也遵循个体化原则,在良好的依从性和安全性条件下进行运动方案的选择,各种运动的效果均较小,包含高应变速率的运动似乎更有效,但均需要长期坚持运动以维持疗效。     

骨质疏松的数值模拟研究

目的对骨质疏松松质骨的力学性质进行数值模拟研究。方法利用均匀化理论研究骨质疏松松质骨的力学性质。结果松质骨的弹性模量（E）与表观密度（ρ）和断裂度（γ）三者之间的数值关系为E=0．38^3.6p-3.76γ,这一结果不仅具有理论意义．更具有重要的实践价值。结论研究表明松质骨的表观密度和断裂度是影响松质骨力学性质的最主要因素．进一步强调了骨微结构对骨强度的影响。     

Evidence of altered matrix composition in iliac crest biopsies from patients with idiopathic juvenile osteoporosis

Purpose: Idiopathic juvenile osteoporosis (IJO) is a rare condition in children, characterized by bone pain and long bone and vertebral fractures. Previously, IJO bone was solely characterized by histomorphometry and quantitative computed tomography. The goal of this study is to describe IJO bone composition. Materials and methods: Fourier transform infrared imaging (FTIRI), a vibrational spectroscopic technique providing spatially resolved images of chemical composition, was used to determine whether iliac crest biopsies from children with IJO differed in composition from and age- and sex-matched controls, and, as a secondary analysis, whether IJO bone showed the same disease dependent change in composition as do iliac crest bone biopsies from women with post-menopausal osteoporosis (PMO). Wilcoxon rank tests and linear regressions were used to analyze FTIRI variables (mineral-to-matrix ratio, carbonate-to-phosphate ratio, crystallinity, acid phosphate substitution, collagen maturity) and their individual pixel distributions (heterogeneity). Results: Mineral-to-matrix ratio was comparable in IJO and age-matched controls. Contrastingly, collagen maturity (also known as collagen cross-link ratio) was higher in cortical and cancellous IJO bone compared with juvenile controls. Acid phosphate substitution was greater in IJO cancellous bone than in age-matched controls, suggesting IJO bone mineral is formed more recently, reflecting a slower mineralization process. This agrees with findings of increased heterogeneity for mineral-to-matrix and collagen maturity ratios in IJO cancellous bone. There were negative correlations between cancellous collagen maturity and previously reported histomorphometric bone formation markers. There were no correlations with indices of remodeling. Conclusions: IJO bone, similar to PMO bone, had elevated collagen maturity relative to its age-matched controls. This emphasizes the importance of the collagen matrix for bone health. IJO bone differed from PMO bone as IJO bone contains more recently formed mineral than age-matched controls but has a more mature matrix, whereas in PMO bone both mineral and matrix have older characteristics.     

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.     

骨质疏松的分子遗传学研究进展

遗传因素在骨质疏松的发病中起重要作用。本文简要介绍近年来在骨质疏松相关基因关联分析方面所取得的研究进展,并对新近发现的删基因在骨量维持中作用的研究进展进行了重点介绍,LRP5基因在骨量和骨密度调控中起着关键作用。     

2013 Up-date of the consensus statement of the Spanish Menopause Society on postmenopausal osteoporosis

Postmenopausal osteoporosis is a major female health problem that increases morbidity, mortality and healthcare system costs. Considering that gynecologists are the primary health practitioners involved in the treatment of women with osteoporosis in our country, a panel of experts from the Spanish Menopause Society met to establish a set of criteria and procedures for the diagnosis and treatment of this disease based on the best available evidence and according to the model proposed by the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to elaborate clinical practice guidelines and to classify the quality of the evidence and the strength of the recommendations. These recommendations should be a reference to gynecologist and other health professionals involved in the treatment of postmenopausal women.     

雷公藤甲素对去势小鼠骨质疏松模型破骨细胞分化的影响

目的 探究雷公藤甲素（TP）对去势小鼠骨质疏松模型破骨细胞分化的影响,并探讨其可能的分子机制。方法 建立去势小鼠骨质疏松模型,分为假手术组（Sham组）、卵巢切除去势组（OVX组）、雷公藤甲素组（TP组）、利维爱组（Livial组）,造模后第3天给予对应药物处理。治疗6周后,采用TRAP染色检测左侧股骨干骺端的破骨细胞数量。Micro-CT重建三维骨结构图像,检测左侧胫骨干骺端的骨密度（BMD）、骨小梁数目（Tb.N）、骨体积分数（BV/TV）、骨表面积组织体积比（BS/TV）、骨小梁分离度（Tb.Sp）,ELISA检测外周血中IL-6、TNF-α、骨形成标志物骨钙素（OC）、骨吸收标志物抗酒石酸酸性磷酸酶（TRAcp5b）含量。Western Blot检测右侧股骨组织中p65、p-p65、IκBα、p-IκBα蛋白表达水平。结果 骨小梁周围破骨细胞数量比较：OVX组与Sham组相比明显增加;TP组与OVX组相比明显减少;TP组与Livial组比较,差异无统计学意义。骨参数分析：OVX组与Sham组相比,小鼠骨组织的BMD、Tb.N、BV/TV、BS/TV均显著下降,而Tb.Sp显著升高（P＜0.01）;与OVX组相比,TP组和Livial组骨组织的BMD、Tb.N、BV/TV、BS/TV均显著升高,而Tb.Sp显著下降（P＜0.01）;TP组与Livial组比较,差异无统计学意义（P＞0.05）。IL-6、TNF-α、OC、TRAcp5b含量比较：OVX组的IL-6、TNF-α含量显著高于Sham组（P＜0.01）;各组间OC水平比较,差异无统计学意义（P＞0.05）;OVX组的TRAcp5b水平显著高于Sham组（P＜0.01）。蛋白表达水平：与Sham组相比,OVX组的p65、IκBα表达水平不变,而p-p65和p-IκBα表达水平显著升高（P＜0.01）;TP处理后,p65、IκBα表达水平不变,而p-p65和p-IκBα表达水平却显著降低（P＜0.01）;TP组与Livial组比较,两者间p65、IκBα、p-p65和p-IκBα表达水平差异无统计学意义（P＞0.05）。结论 TP抑制破骨细胞分化,改善了去势小鼠的骨量丢失,其分子机制可能与抑制炎症因子IL-6、TNF-α的表达及NF-κB信号通路的磷酸化水平有关。     

绝经后骨质疏松症与脂代谢的相关性

动脉粥样硬化常与骨质疏松症共存，进一步分析发现脂代谢指标与骨代谢指标有相关性，而且多数用于治疗骨质疏松症的药物同时对血脂有调节作用，所以推测脂代谢与骨代谢有相关性。其机制可能有：脂肪酸可以促进成骨细胞向脂肪细胞的转化及促进前破骨细胞向破骨细胞分化，调节骨髓间质细胞分化的转录因子及信号转导途径，脂代谢与骨代谢的遗传基因有相关性，高脂血症后骨髓内脂肪细胞增多增大压迫微血管使骨头供血明显减少等。     

三种骨质疏松自我评价工具应用于广西壮族妇女的筛检效果比较

目的:评价亚洲骨质疏松自我评价工具(OSTA)、我国妇女骨质疏松筛选工具(OSTC)、自建的壮族妇女骨质疏松自我评价工具(OSTZ)与广西壮族围绝经和绝经后妇女骨密度的关系,比较三种工具对骨质疏松症的筛检能力,探讨其临床应用价值.方法:2009年12月～2013年12月采用超声骨密度仪筛选获得580名40岁以上围绝经和绝经壮族妇女的跟骨骨密度数据,利用体质量和年龄分别计算OSTA指数、OSTC指数与自建的OSTZ指数,并进行比较.结果:OSTA指数、OSTC指数、OSTZ指数与跟骨骨密度值均呈正相关(r=0.601;r=0.623;r=0.619),OSTA与OSTC、OSTZ筛选指数之间呈正相关(r=0.972和r=0.925),OSTC与OSTZ筛选指数之间呈正相关(r=0.988).按两级危险程度分类界值进行判定,OSTA、OSTC及OSTZ的灵敏度分别为75.7％、88.0％、98.4％,特异度分别为30.3％、43.9％、67.5％.受试者工作特征曲线下面积为0.727、0.721、0.705,Kappa系数为0.455、0.450、0.322.结论:OSTA与OSTC应用于广西壮族绝经后妇女骨质疏松症的筛查效果均不太理想,临床应用价值受限.OSTZ指数应用于广西壮族围绝经和绝经后妇女骨质疏松症的筛查效果较为理想,有一定的临床应用价值.     

生长激素、胰岛素样生长因子-Ⅰ与骨质疏松

生长激素（GH）和胰岛素样生长因子Ⅰ（IGF-Ⅰ）对于骨骼的生长发育以及维持骨量和骨密度具有十分重要的作用，GH与IGF-Ⅰ水平下降是导致骨质疏松的机制之一。动物实验和临床研究发现应用GH、IGF-Ⅰ可以改善骨密度、有利于促进骨折愈合，小剂量GH、IGF-Ⅰ治疗骨质疏松有很好的应用前景。本文综述了GH-IGF-Ⅰ轴与骨骼代谢的关系及其在骨质疏松治疗中的进展。     

陶氏健骨汤治疗原发性骨质疏松症的临床效果

目的:观察评价陶氏健骨汤治疗骨质疏松症的临床效果.方法:将120例骨质疏松症患者随机分为治疗组和对照组,治疗组服用陶氏健骨汤,对照组服用钙尔奇D片,观察各组在治疗前、治疗3个疗程(4周为1个疗程)后的临床体征、骨代谢生化指标、性激素、骨形成生化指标、骨吸收生化指标的变化.结果:治疗后两组患者中医症状均减轻,差异有统计学意义(P＜0.05);治疗后组间比较,治疗组腰背疼痛、腰膝酸软、抽筋、步履艰难等症状程度轻于对照组,差异有统计学意义(P＜0.05).治疗结束后,两组甲状旁腺激素(parathyroid hormone,PTH)、血钙(S-Ca)均较治疗前降低,降钙素(calcitonin,cT)较治疗前升高,差异有统计学意义(p＜0.05);治疗组患者治疗后性激素(E2、T)含量升高,差异有统计学意义(P＜0.05);对照组患者治疗前后性激素(E2,T)变化差异无统计学意义(p＞0.05).两组患者治疗后碱性磷酸酶(alkaline phosphatase,ALP)、骨钙素(boneglaprotein,BGP)均较治疗前上升(P＜0.05);且治疗后组间比较,治疗组ALP,BGP均高于对照组,差异有统计学意义(P＜0.05).两组患者治疗后U-HYP/Cr,U-Ca/Cr,TRAP均明显下降,差异有统计学意义(p＜0.05);治疗后,治疗组U-HYP/Cr,U-Ca/Cr,TRAP均低于对照组,差异有统计学意义(P＜0.05).结论:陶氏健骨汤具有提高雌激素水平,抑制骨吸收,促进骨形成等功能,是治疗骨质疏松的有效方药.