雌激素受体与绝经后骨质疏松症

检索Pubmed数据库和中国期刊全文数据库文献，总结雌激素受体与绝经后骨质疏松症的关系。雌激素受体以雌激素受体α和雌激素受体β两种亚型广泛存在于人体内。雌激素根据其结合的受体亚型，选择性激活细胞内信号传导途径，表现出多种生物学活性。雌激素对骨吸收的调控作用是通过某些细胞因子的介导和直接对破骨细胞作用完成的。近年来对选择性雌激素受体调节剂对两种不同受体亚型的特异性作用的研究已成为热点。     

雌激素对骨代谢的调节作用

雌激素对于维持骨吸收与骨形成的平衡具有极其重要的作用。雌激素对骨代谢具有直接作用。雌激素通过破骨细胞和成骨细胞受体，限制骨转换，抑制骨吸收，提高骨密度。雌激素通过骨代谢调节因子、甲状旁腺激素等发挥其间接调节作用。植物雌激素及其衍生物分子结构与雌激素类似，可以与雌激素受体结合发挥雌激素作用。植物雌激素已成为当前雌激素替代疗法的研究热点。     

雌激素对骨代谢的调节作用

雌激素对于维持骨吸收与骨形成的平衡具有极其重要的作用。雌激素对骨代谢具有直接作用。雌激素通过破骨细胞和成骨细胞受体,限制骨转换,抑制骨吸收,提高骨密度。雌激素通过骨代谢调节因子、甲状旁腺激素等发挥其间接调节作用。植物雌激素及其衍生物分子结构与雌激素类似,可以与雌激素受体结合发挥雌激素作用。植物雌激素已成为当前雌激素替代疗法的研究热点。     

雌激素受体对代谢综合征的影响研究进展

<正>谢综合征(Metabolic,MS)是一种代谢紊乱症候群,包括腹部肥胖、胰岛素抵抗、高甘油三酯血症和高血压等症状。流行病学调查结果表明,女性在绝经后的MS发病概率大幅提升,雌激素水平的下降对MS的病发有明显的影响^[1]。在其病发后会明显增加心血管疾病、糖尿病和癌症的患病风险^[2]。因此,MS对于绝经后的女性健康产生了严重的威胁。同时作为绝经后雌激素水平变化的这一明显特征,对于雌激素及雌激素受体(Estrogen Receptor,ER)与MS的发病机制的研究也愈发受到研究人员的关注。本文就ER对MS中的肥胖,脂代谢和糖代谢展开讨论与综述。     

雌激素受体与大肠癌

近年来，随着肿瘤研究的不断深入，许多学者在非性激素靶器官肿瘤中发现了雌激素受体(estrogen receptor，ER)，其中尤以大肠癌为多。从此大肠癌与性激素的关系成了许多学者研究的热点。本文对雌激素及其受体与大肠癌的关系研究进展综述如下。     

雌激素受体亚型ERα、ERβ在乳腺癌中的表达及意义

本研究采用免疫组织化学法对100例国人女性不同阶段乳腺组织中雌激素受体α(ERα)、雌激素受体β(ERβ)进行检测,探讨其与一些肿瘤病理参数和生物学标志物(是否绝经、肿瘤大小、淋巴结转移情况、组织学类型、肿瘤分期、C-erbB-2表达)之间的关系,以期为有关ERα、ERβ与乳腺癌发生发展关系的深入研究以及临床判断乳腺癌预后及指导治疗提供帮助。     

乳腺癌雌激素受体亚型研究进展

乳腺癌是妇女中最常见的恶性肿瘤，其发病率正在逐步上升。乳腺癌是激素依赖性肿瘤，受雌激素和孕激素的调控，在多数乳腺癌组织中均发现有两种激素受体^[1]：雌激素受体（estrogen receptors，ER）和孕激素受体（progesterone receptors，PR）的表达，内源性雌激素参与乳腺上皮的生长分化，在乳腺癌的发生、发展中起至关重要的作用，而雌激素的作用又是由受体ER所介导的^[2]。     

雌激素受体β的研究进展

雌激素受体β（ERβ）具有重要的生理和病理意义，它与雌激素受体α结构相似，但在组织学分布方面不尽相同。本文就ERβ的分子生物学特性、组织学分布及与疾病的关系等作一综述。     

雌激素受体基因多态性的研究进展

雌激素受体是雌激素发挥作用的关键 ,对雌激素受体结构和功能的研究有助于一些疾病的治疗。本文就雌激素受体分子生物学物征、基因多态性及其检测方法 ,以及雌激素受体基因多态性与疾病的关系等作一综述     

绝经后女性脂质代谢与雌激素受体基因多态性的关系研究

绝经后女性患冠心病的危险性逐渐增高,过早停经的女性和双侧卵巢切除的女性冠心病患病危险性亦明显增加,而对绝经后妇女行雌激素替代治疗可明显降低其心血管事件和心血管疾病病死率。以上可提示雌激素对心血管系统具有保护性作用,但目前仍不能完全理解雌激素对心血管系统的保护作用是否完全依赖经典的雌激素受体,也有报道认为还存在其他机制。但其基本机制至少有以下两点：①对脂质代谢的影响;②直接作用于血管壁。内源性和外源性雌激素均可使低密度脂蛋白胆固醇减低,使高密度脂蛋白胆固醇升高。另外,最近一项关于冠状动脉尸检标本的研究显示,绝经后女性雌激素受体表达的存在与冠状动脉粥样硬化的程度呈负相关。基于以上,我们做了雌激素受体两种多态性（pvuⅡ多态性和xbaⅠ多态性）与女性冠心病患者脂质代谢的关系研究。在以前的报道中,也曾见到雌激素受体基因多态性与血脂关系的研究,认为二者无相关性,但我们注意到其中女性所占比例甚小（病例组22例,对照组12例）,故我们认为扩大样本量做进一步研究仍有必要。     

Age-related transformation of bone metabolism

Bone mass reaches peak bone mass by the age of about from eighteen to twenty in men and women, since then it is reduced with aging every year. Decrease in bone mass with aging is classified postmenopausal osteoporosis and senile osteoporosis of involutional osteoporosis. Bone mass is reduced suddenly in menopausal period on postmenopausal osteoporosis, but it is reduced slowly in men and women on senile osteoporosis. We will give an outline of age-related transformation of bone metabolism classified from growth period to maturity period, menopausal period in men and women, and aging period.     

Osteoporosis in men: epidemiology, diagnosis, prevention, and treatment

BACKGROUND: Osteoporosis and fragility fractures in men account for substantial health care expenditures and decreased quality of life. OBJECTIVE: This article reviews the most current information about the epidemiology, diagnosis, prevention, and treatment of osteoporosis in men. METHODS: Relevant literature was identified through a search of MEDLINE (1966-June 2003) limited to English-language studies in men. The search terms included fractures, bone density, or osteoporosis plus either epidemiology, diagnosis, prevention, control, or therapy. Additional search terms included specific subtopics (eg, bisphosphonates, calcium, exercise, parathyroid hormone). The authors contributed additional relevant publications. RESULTS: Morbidity after fragility fracture is at least as high in men as in women, and the rate of fracture-related mortality 1 year hip fracture is approximately double in men compared with women. The bioavailable fraction of testosterone slowly declines into the ninth decade in men. There is evidence that the effect of estrogen on bone is greater than that of testosterone in men. Diagnosing osteoporosis in men is complicated by a lack of consensus on how it should be defined. Significant risk factors for osteoporosis or fracture include low bone mineral density, previous fragility fracture, maternal history of fracture, marked hypogonadism, smoking, heavy alcohol intake or alcoholism, low calcium intake, low body mass or body mass index, low physical activity, use of bone-resorbing medication such as glucocorticoids, and the presence of such conditions as hyperthyroidism, hyperparathyroidism, and hypercalciuria. Prevention is paramount and should begin in childhood. During adulthood, calcium (1000-1500 mg/d), vitamin D (400-800 IU/d), and adequate physical activity play crucial preventive roles. When treatment is indicated, the bisphosphonates are the first choice, whereas there is less support for the use of calcitonin or androgen therapy. Parathyroid hormone (1-34) is a promising anabolic therapy. There is also strong evidence for the use of bisphosphonates for the treatment of glucocorticoid-induced osteoporosis.     

Bone mineral density of vertebrae,proximal femur and os calcis in normal Greek subjects as assessed by dual-energy X-ray absorptiometry: comparison with other populations

Dual energy X-ray absorptiometry (DXA) is an established method for the detection of even small changes in bone mineral density (BMD). It thus allows the earliest possible diagnosis of osteopenia, with consequent prompt estimation of fracture risk. However, for proper evaluation of densitometry results it is essential that a comparison with reference BMD values of normal age- and sex-matched persons from the same population be performed. For this purpose we determined bone density of the L2–L4 vertebrae, the L3 vertebra in the lateral projection, the proximal femur and the os calcis in a cross-sectional study of 168 men and 244 women from the Greek population. The age range of the subjects was 20–80 years. Peak bone mass for both sexes was attained in the 30–35 year age group for the vertebrae and in the 25–30 year age group for the proximal femur and os calcis. Mean annual vertebral bone loss calculated on cross-sectional data ranged from 0.1% to 0.22% for women <50 years and from 1.3% to 1.6% for those >50 years, whereas in men the range was from 0.36% to 0.64% for the whole age spectrum. Regarding femoral neck, the values were 0.3% (women <50 years), 1.2–1.5% (>50 years) and 0.6–0.8% for men. Total bone loss between ages 20 and 70 was 29.5% for the vertebrae and 32% for the femoral neck in women, whereas the values for men were 19.5% and 29% respectively. A positive correlation was observed between bone density, body weight and body height in both sexes. Body mass index correlated significantly with density only in postmenopausal women. Compared with North American, Finnish and German populations, Greek men presented with lower BMD values in the decades above 40 years. Greek women exhibited lower vertebral BMD values than those from the USA, Germany and Japan (50–60 age group), whereas they did not differ from those of Finnish women. However, femoral neck BMD in Greek women was higher than in Japanese women in all age groups.     

Does alternate-day cloprednol therapy prevent bone loss? A longitudinal double-blind, controlled clinical study

Osteoporosis is a serious side effect of systemic treatment with steroids. Cloprednol, a synthetic glucocorticoid with an anti-inflammatory potency twice that of prednisone, causes less calcium and nitrogen excretion than does prednisone in equipotent doses. Therefore a double-blind study was undertaken comparing the effects of alternate-day cloprednol and prednisone therapy on bone mineral density in 39 patients (cloprendol: 13 men and 8 women aged 48.5 +/- 2.8 years; prednisone: 9 men and 9 women aged 49.7 +/- 1.7 years) with lung diseases. Ten patients with asthma (9 men and 1 woman aged 37.8 +/- 3.7 years) inhaling daily beclomethasone served as control subjects. Trabecular and total bone density of the distal tibia and radius was determined quarterly during 1 year with a special-purpose computed tomographic system. Initial mean trabecular bone density of the patients receiving cloprednol and prednisone was 17% below normal. After a treatment period of 1 year, we found a loss of radial trabecular bone density (mean +/- SEM) of 1.33% +/- 0.49% in the cloprednol group and 2.38% +/- 0.69% in the prednisone group. In postmenopausal women, prednisone but not cloprednol therapy caused significant (p less than 0.01) trabecular bone loss (5.29% +/- 0.99% versus 0.70% +/- 0.65%). The control group lost 0.91% +/- 0.79%. Loss of cortical bone was insignificant in all three groups. In post-menopausal women, 1 year of alternate-day cloprednol therapy was associated with significantly less bone loss than was prednisone therapy in equipotent dosages.     

Bone turnover in healthy adults measured by whole body retention and urinary excretion of 99mTc-MDP. Normalization by bone mass

Whole body retention (WBR) and urinary excretion (UE) of 99mTc-diphosphonate, two complementary methods of measuring the total bone turnover, were performed in 161 normal subjects, 82 women and 79 men, aged 20-70 years. Both WBR and UE were a function of age in the women, whereas there were no age-dependent differences in the men. Between the women and men in identical age groups, the differences did not reach significance. Total body bone mineral (TBBM) was measured by dual photon absorptiometry (DPA) in all subjects. This was done in order to obtain expressions for bone turnover per bone mass as a function of age and sex. This correction emphasized the general picture seen in the raw WBR and UE data: bone turnover was constant in the men throughout life and in the women before the menopause, and only moderate differences were found between the sexes before the age of 50. After this age the mean female values increased sharply. It is noteworthy that none of the postmenopausal subjects showed low turnover values. Our data clearly demonstrate that an increase in bone turnover is part of the pathophysiology of the well-known bone loss in postmenopausal women.     

Osteoporosis in men: prevalence and investigation

In the past, osteoporosis was thought to affect only women; however, in the last decade it has become apparent that osteoporosis is common in men, particularly elderly men. Osteoporosis affects as many as 2 million men in the United States. Osteoporosis most commonly affects the hip and the lumbar vertebrae, but other bones, such as the radius, tibia, and ribs, may also fracture. The main feature of the etiology of the disease is that low bone mineral density results in increased susceptibility to bone fracture. The World Health Organization has defined osteoporosis as a bone mineral density T-score value >2.5 SDs below the mean observed in young adult women. Although the validity of this score for evaluating men has been questioned and it is not clear whether a male or female reference database should be used, it is nonetheless often used in this way. The disease affects men differently than women in a number of respects. It manifests itself later in life in men than in women, probably because men initially have greater bone mass. Mortality and morbidity associated with hip fractures are high in all elderly individuals, but they are substantially higher in men than in women. Unlike in women, there is an underlying cause for the osteoporosis in almost half of affected men. Thus, for elderly men, a complete history and physical examination may reveal some remediable conditions; treating these may stop further progression of the disease and prevent further morbidity or mortality. Corticosteroid therapy for arthritis or asthma is a common cause of osteoporosis in elderly men. Hypogonadism is a recognized cause of osteoporosis in men treated for carcinoma of the prostate with androgen withdrawal therapy; treatments to modify the effects of these agents on bone are available. Consumption of large amounts of alcohol will eventually result in osteoporosis in some elderly men. Moreover, alcohol can predispose confused elderly patients to falls and to fracture bones that are already osteoporotic. Hyperthyroidism is associated with a reduction in bone mineral density and an increased likelihood of bony fracture. A careful search for undiagnosed hyperthyroidism in elderly osteoporotic men may prove worthwhile. Vitamin D deficiency is common among older men and could contribute to an increase in fractures. Routine analyses of blood and biochemistry should be carried out in any older male patient with newly diagnosed osteoporosis. Dual x-ray energy absorptiometry should be performed on every new patient with newly diagnosed osteoporosis.     

Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spinal osteoporosis.

Patterns of bone loss in the axial and the appendicular skeleton were studied in 185 normal volunteers (105 women and 82 men; age range, 20--89 yr) and in 76 women and 9 men with vertebral fractures due to osteoporosis. Bone mineral density was measured in vivo at the lumbar spine (predominantly trabecular bone) by dual photon absorptiometry and at the midradius (greater than 95% cortical bone) and distal radius (75% cortical and 25% trabecular bone) by single photon absorptiometry. In normal women, bone diminution from the vertebrae began in young adulthood and was linear. In the appendicular skeleton, bone diminution did not occur until age 50 yr, was accelerated from aged 51 to 65 yr, and then decelerated somewhat after age 65 yr. Overall bone diminution throughout life was 47% for the vertebrae, 30% for the midradius, and 39% for the distal radius. In normal men, vertebral and appendicular bone diminution with aging was minimal or insignificant. Mean bone mineral density was lower in patients with osteoporosis than in age- and sex-matched normal subjects at all three scanning sites, although spinal measurements discriminated best; however, there was considerable overlap. By age 65 yr, half of the normal women (and by age 85 yr, virtually all of them) had vertebral bone mineral density values below the 90th percentile of women with vertebral fractures and, thus, might be considered to have asymptomatic osteoporosis. For men, the degree of overlap was less. The data suggest that disproportionate loss of trabecular bone from the axial skeleton is a distinguishing characteristic of spinal osteoporosis.     

Quantitative Determination of Putrescine,Cadaverine, Spermine and Spermidixe

Plasma bone Gla protein (BGP) was determined by radio-immunoassay in 266 healthy adults, men (n=132) and women (n = 134), aged 20–79 years. In the women aged 30–69 years, plasma BGP increased significantly with age (r = 0.44. p<0.001). and a particularly steep increase was seen from 1.1 ± 0.5 (mean±1 SD) in the fifth decade to 2.0 ± 1.4 nmol/l in the seventh decade. In men, aged 30–69 years, no correlation was found between plasma BGP and age (r= ?0.07, NS). Plasma bone Gla protein is removed from the circulation mainly by the kidneys and the increased plasma BGP in the women could be caused by decreased renal clearance. The interrelationship was analysed by means of partial correlation. When creatinine clearance was held constant in women, BGP still correlated positively with age (r = 0.40. p<0.001). but not with creatinine clearance (r=0.003, NS) when age was fixed. Plasma BGP was significantly increased above normal in 35 patients with chronic renal failure (10.2±14.6 nmol/l). Non-linear regression analysis showed that plasma BGP was within the normal range when 24-h creatinine clearance was greater than 30 ml/min, and large increases in plasma BGP did not occur until the 24-h creatinine clearance was below 20 ml/min. We conclude that, in normal subjects and patients with mild to moderate renal failure, plasma elevations of BGP reflect increased bone turnover rather than decreased renal clearance.     

Osteoporosis knowledge, health beliefs, and DXA T-scores in men and women 50 years of age and older

PURPOSE: To compare the knowledge of osteoporosis, revised health belief model variables (RHBM), and DXA (dual energy x-ray absorptiometry) T-scores among men and women 50 years of age and older. DESIGN: This was a secondary analysis that used 218 healthy community-based women 50 to 65 years of age and 226 healthy community-based men >or=50 years of age. Data for women were collected for 18 months during 2001-2003, and data for men were collected for 18 months during 2004-2006. The variables were knowledge of osteoporosis, RHBM variables (susceptibility, seriousness, benefits and barriers of calcium intake and of exercise, health motivation, self-efficacy of calcium intake and exercise), and DXA T-scores. METHOD: The women and men completed an osteoporosis questionnaire prior to having a DXA screening test. A total of 190 women and 187 men had DXA scans. FINDINGS: More than half of the sample had abnormal bone density scans. Knowledge of osteoporosis was low for women and even lower for men. Seven of the nine health belief variables were associated with gender. Women perceived osteoporosis to be serious and that they were susceptible. Men did not perceive osteoporosis to be serious or that they were susceptible. Men were more health motivated and more confident of their ability to engage in exercise.     

Characterization of serum alkaline phosphatase isoenzymes by affinity electrophoresis in agarose gel containing lectin combined with agar gel electrophoresis

The combined use of affinity electrophoresis in agarose gel containing lectin and of agar gel electrophoresis for the quantitation of liver, bone, biliary and intestinal alkaline phosphatase isoenzymes is described. Sera from patients with various diseases and from normal subjects (blood donors) have been analyzed. Data from normal subjects show that the bone isoenzyme is the predominant fraction (about 62%) in adults. The relative proportions of the alkaline phosphatase isoenzymes are similar in both sexes in adulthood (21-50 years). The higher alkaline phosphatase activity found in men than in women (ages 21-50 years) is due to higher values for both liver and bone isoenzymes. The difference between men and women tends to decrease after the age of 50 mainly due to an increase of the bone isoenzyme in women.