BACKGROUND & AIMS: Calcitriol has been widely used in the management of osteoporosis, but its efficiency is a matter of controversy. It is not known whether combinations of calcitriol and antiresorptive agents such as etidronate and calcitonin are superior to calcitriol alone in the treatment of postmenopausal osteoporosis. To make this determination, 30 Turkish women with postmenopausal osteoporosis between 45 and 68 years of age were randomized to receive either intermittent cyclical etidronate (400 mg/day, for 14 days) followed by 60 days of cyclical calcitriol therapy 0.25 microg twice daily (group 1; n = 10), or calcitriol 0.25 microg twice daily (group 2; n = 10), or calcitriol 0.25 microg/day in combination with 100 IU intranasal salmon calcitonin taken every other day (group 3; n = 10) through a 1-year period. Bone mineral density (BMD) of lumbar spine (L2 to L4) was determined for each patient by dual-photon absorptiometry (153Gd) at baseline, after 6 months, and at the end of the study. There was no significant difference among groups with respect to mean spinal BMD at baseline, after 6, and after 12 months. No significant spinal BMD changes occurred in any group from baseline, after 6 months, and after 12 months. Four patients in groups 1 and 2 and five patients in group 3 developed hypercalcemia at least once during therapy. Hypercalciuria occurred at least once in 9, 10, and 7 patients in groups 1, 2, and 3, respectively. One patient in group 2 developed a renal stone at the end of the study. Mean urine hydroxyproline levels did not change significantly in any group with respect to baseline. The data suggest that one-year treatment with calcitriol, given either alone or in combination with antiresorptive agents, does not improve spinal BMD in Turkish women with postmenopausal osteoporosis, and is associated with a high rate of adverse events.

背景与目标： 骨化三醇已广泛用于骨质疏松症的治疗，但其效率仍存在争议。尚不清楚骨化三醇和抗吸收剂 (如依替膦酸盐和降钙素) 的组合在绝经后骨质疏松症的治疗中是否优于单独的骨化三醇。为了做出这一决定，30名年龄在45至68岁之间的绝经后骨质疏松症土耳其妇女被随机分配接受间歇性周期性依替膦酸盐 (400毫克/天，持续14天)，然后接受60天的周期性骨化三醇治疗，0.25每天两次 (组1; n = 10)，或骨化三醇0.25 microg每天两次 (组2; n = 10)，或骨化三醇0.25 microg/天与100 IU鼻内鲑鱼降钙素组合，每隔一天服用 (组3; n = 10)，持续1年。在基线，6个月后和研究结束时，通过双光子吸收法 (153Gd) 测定每位患者的腰椎 (L2至L4) 的骨矿物质密度 (BMD)。在基线，6个月后和12个月后，各组之间的平均脊柱BMD没有显着差异。从基线，6个月后和12个月后，任何组均未发生明显的脊柱BMD变化。第1组和第2组中的4名患者和第3组中的5名患者在治疗期间至少出现一次高钙血症。高钙尿症分别在第1、2和3组的9、10和7名患者中至少发生一次。第2组中的一名患者在研究结束时出现了肾结石。任何组的平均尿羟脯氨酸水平相对于基线没有明显变化。数据表明，单独或与抗吸收剂联合使用骨化三醇治疗一年不会改善土耳其绝经后骨质疏松症妇女的脊柱BMD，并且与不良事件的发生率很高有关。

BACKGROUND & AIMS: :Osteoporosis is characterized by low bone mass and by changes in the microarchitecture of the bone. This leads to reduced bone stability and altered suscebtibility to fractures. Bone remodelling in healthy persons is characterized by a balance between bone resorption and bone formation. At the cellular level, bone remodelling is regulated by osteoclast and osteoblast activity. During bone loss, there is an imbalance, osteoclast activity being more pronounced. Therefore, the influende of estrogens, Wnt and the RANK/ RANKL/OPG system on osteoclastogenesis and osteoclast activity has been investigated. The RANK/RANKL/OPG-System is actively involved in the differentiation and function of osteoclasts and seems to play a central part in most pathophysiological mechanisms that are active in osteoporosis.

背景与目标： : 骨质疏松症的特征是骨量低和骨微结构的变化。这会导致骨骼稳定性降低，并改变对骨折的敏感性。健康人的骨重塑的特征是骨吸收和骨形成之间的平衡。在细胞水平上，骨重塑受破骨细胞和成骨细胞活性的调节。在骨丢失期间，存在不平衡，破骨细胞活性更加明显。因此，研究了雌激素，Wnt和RANK/ RANKL/OPG系统对破骨细胞生成和破骨细胞活性的影响。RANK/RANKL/OPG系统积极参与破骨细胞的分化和功能，并且似乎在骨质疏松症中活跃的大多数病理生理机制中起着核心作用。

BACKGROUND & AIMS: :The cause-effect relationship between iron deficiency anemia (IDA) and osteoporosis has not been established in the general population. Thus, the current longitudinal study determined the role of IDA as a risk factor for osteoporosis by analyzing a large nationwide population-based sample. In a sample of 1,000,000 randomly sampled individuals from the 1998-2012. Taiwan National Health Insurance Research Database, patients with IDA (case group (n = 35,751)) and individuals without IDA (control group (n = 178,755)) were compared. Patients who were <20 years of age and who had pre-existing osteoporosis prior to the diagnosis of IDA were excluded. Each patient with IDA was age- and gender-matched to five individuals without IDA. The diagnoses of IDA and osteoporosis (coded using ICD-9CM) were further confirmed with blood test results and X-ray bone densitometry to ensure the accuracy of the diagnoses. Osteoporosis occurred more often among patients with IDA compared to individuals without IDA (2.27% vs. 1.32%, p < 0.001). Cox proportional hazard analysis revealed that the risk for osteoporosis was significantly higher in the case than the control group (hazard ratio (HR) = 1.74; 95% CI = 1.61-1.88) and remained similar after adjustment for covariates (adjusted HR = 1.81; 95% CI = 1.67-1.97). Compared with individuals without IDA, the risk for osteoporosis was even higher for patients with IDA who received intravenous ferrum therapy (adjusted HR = 2.21; 95% CI = 1.85-2.63). In contrast, the risk for osteoporosis was reduced for patients with IDA who received a blood transfusion (adjusted HR = 1.47; 95% CI = 1.20-1.80). As a predictor, prior IDA is a significant and independent risk factor for development of osteoporosis.

背景与目标： : 在普通人群中，缺铁性贫血 (IDA) 与骨质疏松症之间的因果关系尚未建立。因此，当前的纵向研究通过分析大量全国基于人群的样本来确定IDA作为骨质疏松症危险因素的作用。在从1998-2012中随机抽取的1,000,000个样本中。对台湾全民健康保险研究数据库、IDA患者 (病例组 (n = 35,751)) 和无IDA患者 (对照组 (n = 178,755)) 进行比较。年龄 <20岁且在诊断IDA之前已有骨质疏松症的患者被排除。每位IDA患者的年龄和性别与五名没有IDA的患者相匹配。通过血液检查结果和x射线骨密度法进一步确认IDA和骨质疏松症 (使用ICD-9CM编码) 的诊断，以确保诊断的准确性。与没有IDA的个体相比，IDA患者中更经常发生骨质疏松症 (2.27% vs. 1.32%，p <0.001)。Cox比例风险分析显示，该病例的骨质疏松症风险显着高于对照组 (风险比 (HR) = 1.74; 95% CI = 1.61-1.88)，并且在校正协变量后保持相似 (调整后HR = 1.81; 95% CI = 1.67-1.97)。与没有IDA的个体相比，接受静脉铁治疗的IDA患者的骨质疏松症风险更高 (调整后的HR = 2.21; 95% CI = 1.85-2.63)。相比之下，接受输血的IDA患者的骨质疏松症风险降低 (调整后的HR = 1.47; 95% CI = 1.20-1.80)。作为预测因素，先前的IDA是骨质疏松症发生的重要且独立的危险因素。

BACKGROUND & AIMS: OBJECTIVE:To determine genome-wide methylation profiles of bone from patients with hip osteoarthritis (OA) and those with osteoporotic (OP) hip fractures. METHODS:Trabecular bone pieces were obtained from the central part of the femoral head of 27 patients with hip fractures and 26 patients with hip OA. DNA was isolated, and methylation was explored with Illumina methylation arrays. RNA was extracted, pooled, and deep-sequenced to obtain the whole transcriptome. Differentially methylated regions were identified, and connections between genes with differentially methylated regions were explored by pathway and text-mining analyses. RESULTS:After quality control, methylation of 23,367 CpG sites (13,463 genes) was analyzed. There was a genome-wide inverse relationship between methylation and gene expression in both patient groups. Comparison of OP and OA bones revealed 241 CpG sites, located in 228 genes, with significant differences in methylation (false discovery rate<0.05). Of them, 217 were less methylated in OP than in OA. The absolute methylation differences were >5% in 128 CpG sites and >10% in 45 CpG sites. The differentially methylated genes were enriched for association with bone traits in the genome-wide association study catalog. Pathway analysis and text-mining analysis with Gene Relationships Across Implicated Loci software revealed enrichment in genes participating in glycoprotein metabolism or cell differentiation, and particularly in the homeobox superfamily of transcription factors. CONCLUSION:Genome-wide methylation profiling of bone samples revealed differentially methylated regions in OP and OA. These regions were enriched in genes associated with cell differentiation and skeletal embryogenesis, such as those in the homeobox superfamily, suggesting the existence of a developmental component in the predisposition to these disorders.

背景与目标：

BACKGROUND & AIMS: :The effect of body mass index (BMI) and obesity on apolipoprotein (apo) A-I levels and kinetics was examined by gender. Apo A-I kinetics were determined with a primed, constant infusion of deuterated leucine in the fed state in 19 men and 13 postmenopausal women. Compared with nonobese men, nonobese women had a higher level of high-density lipoprotein cholesterol (HDL-C) and apo A-I due to a 48% higher apo A-I production rate (PR) (P = .05). Obesity had no significant effects on apo A-I kinetics in women. In contrast, compared with nonobese men, obese men had a 9% lower apo A-I level due to a 64% higher fractional catabolic rate (FCR) partially offset by a 47% higher PR. Obese women had a 52% higher HDL-C than obese men (50 vs 33 mg/dL, respectively; P = .012), a finding related to the faster apo A-I FCR in obese men. BMI was directly correlated with apo A-I FCR (r = 0.84, P < .001) and PR (r = 0.79, P < .001) in men but not in women. Sixty-two percent of the variability in PR and 71% of the variability in FCR were due to BMI in men and only 3% and 23%, respectively, in women. In conclusion, BMI has a significant effect on apo A-I PR and FCR in men but not in women.

背景与目标： : 通过性别检查了体重指数 (BMI) 和肥胖对载脂蛋白 (apo) A-I水平和动力学的影响。在19名男性和13名绝经后女性中，通过在进食状态下持续不断地输注氘代亮氨酸来确定Apo A-I动力学。与非肥胖男性相比，非肥胖女性的高密度脂蛋白胆固醇 (hdl-c) 和apo a-I水平较高，原因是apo A-I的生产率 (PR) 48% 较高 (P = .05)。肥胖对女性的apo A-I动力学没有显着影响。相反，与非肥胖男性相比，肥胖男性的apo a-I水平9% 较低，这是由于64% 较高的分解代谢率 (FCR) 部分被47% 较高的PR抵消。肥胖女性的hdl-c比肥胖男性高52% (分别为50 vs 33 mg/dL; P = .012)，这一发现与肥胖男性的apo a-I FCR更快有关。BMI与男性的apo A-I FCR (r = 0.84，P <.001) 和PR (r = 0.79，P <.001) 直接相关，而女性则不相关。PR变异性的60 2% 和FCR变异性的71% 是由于男性的BMI，而女性分别只有3% 和23%。总之，BMI对男性的apo a-I PR和FCR有显着影响，而女性则没有。

BACKGROUND & AIMS: INTRODUCTION:Two global, double-blind, placebo- and active-controlled, phase-3 studies (2-year prevention (n = 1583) and 3-year treatment (n = 7492)) have shown that bazedoxifene (BZA) is safe and effective for prevention and treatment of postmenopausal osteoporosis. OBJECTIVE:To evaluate the efficacy/safety of BZA according to baseline kidney function. METHODS:Data for the BZA 20- and 40-mg and placebo groups from both studies were integrated for assessment of bone turnover markers (BTMs), bone mineral density (BMD), and fracture incidence (treatment study only). Safety was assessed using integrated data for the BZA, placebo, and raloxifene 60-mg groups from both studies. Baseline glomerular filtration rate (GFR) was estimated by the Modification of Diet in Renal Disease Study equation; among subjects with baseline GFR, renal function categories were defined by GFR (ml/min per 1.73 m(2)): normal (GFR ≥ 90; n = 1982), mild impairment (60 ≤ GFR < 90; n = 6032), or moderate/severe impairment (GFR < 60; n = 723). RESULTS:Demographics were similar across treatment groups and within GFR subgroups. Across GFR subgroups, BZA 20 and 40 mg reduced BTM levels and improved lumbar spine and total hip BMD versus placebo. At month 24, there were significant treatment-by-GFR (p = 0.003) and treatment-by-serum creatinine (p = 0.034) interactions for the increase in lumbar spine BMD versus placebo. Fracture incidence was lower with BZA than placebo across all GFR categories, with no treatment-by-GFR interaction. There were no significant differences among treatment groups in incidences of overall, serious, or renal-related adverse events across GFR subgroups. CONCLUSIONS:Mild to moderate kidney impairment did not affect the efficacy and safety of BZA in postmenopausal women.

背景与目标：

BACKGROUND & AIMS: :Osteoporosis maintains a special position in today's medicine, regarding both its growing incidence and its clinical and social consequences--fractures, leading to the loss of self-dependence, disabilities and higher mortality rates. It was thought for many years that osteoporosis affected mainly women after menopause. At present, it is known that the problem concerns men, as well. In the present review, similarities and differences between osteoporosis in either sex are discussed, concentrating on epidemiological and pathogenetic aspects, as well as on therapeutic differences.

背景与目标： : 骨质疏松症在当今医学中保持着特殊的地位，无论是其发病率的增长还是其临床和社会后果-骨折，导致丧失自我依赖性，残疾和更高的死亡率。多年来，人们一直认为骨质疏松症主要影响更年期后的妇女。目前，众所周知，这个问题也涉及男性。在本综述中，讨论了两种性别的骨质疏松症之间的异同，重点是流行病学和致病方面以及治疗上的差异。

BACKGROUND & AIMS: INTRODUCTION:Stress urinary incontinence (SUI) is a chronic disease which occurs in 50% of women with urinary incontinence. It is estimated that in association with a longer life span and ageing of the population, this disorder will become even more prevalent and will exert an increasingly stronger effect on the deterioration of the quality of life. OBJECTIVE:The objective of the study is analysis of the factors affecting the occurrence of SUI. METHODOLOGY:The analysis covered 260 patients aged 27-82. The criterion of enrolment into the study was: diagnosis of SUI without disorders of pelvi-genital statics, and negative obstetric history (nulliparous and non-pregnant women). The investigations covered, among other things, the effect surgeries in the area of the lesser pelvis, body mass index (BMI), cigarette smoking, concomitant internal diseases, and hormonal therapy, with consideration of the division into two groups: women before and after menopause. Statistical analysis was performed by means of chi 2 Pearson, t-Student test, and Fisher-Freeman-Halton test for p<0.05. RESULTS:The results of the analysis unequivocally indicate that the age of patients (p=0.0001), body mass index (BMI) (p=0.0001), and surgical procedure for the removal of the uterus by laparotomy (p=0.0001) exert the greatest effect on the occurrence of SUI in pre- and postmenopausal women. The effect of the remaining etiologic factors is rather controversial. CONCLUSION:A comprehensive analysis of risk factors may contribute to the improvement of the results of treatment and quality of life of pre- and postmenopausal patients.

背景与目标：

BACKGROUND & AIMS: To assess the cost-effectiveness of interventions to prevent osteoporosis, it is necessary to estimate total health care expenditures for the treatment of osteoporotic fractures. Resources utilized for the treatment of many diseases can be estimated from secondary databases using relevant diagnosis codes, but such codes do not indicate which fractures are osteoporotic in nature. Therefore, a panel of experts was convened to make judgments about the probabilities that fractures of different types might be related to osteoporosis according to patient age, gender, and race. A three-round Delphi process was applied to estimate the proportion of fractures related to osteoporosis (i.e., the osteoporosis attribution probabilities) in 72 categories comprised of four specific fracture types (hip, spine, forearm, all other sites combined) stratified by three age groups (45-64 years, 65-84 years, 85 years and older), three racial groups (white, black, all others), and both genders (female, male). It was estimated that at least 90% of all hip and spine fractures among elderly white women should be attributed to osteoporosis. Much smaller proportions of the other fractures were attributed to osteoporosis. Regardless of fracture type, attribution probabilities were less for men than women and generally less for non-whites than whites. These probabilities will be used to estimate the total direct medical costs associated with osteoporosis-related fractures in the United States.

背景与目标： 为了评估预防骨质疏松症的干预措施的成本效益，有必要估算用于治疗骨质疏松性骨折的医疗保健总支出。可以使用相关的诊断代码从二级数据库中估算用于治疗许多疾病的资源，但是这些代码并未指出哪些骨折本质上是骨质疏松的。因此，召集了一个专家小组，根据患者的年龄，性别和种族来判断不同类型的骨折可能与骨质疏松症有关的可能性。采用三轮Delphi程序来估计与骨质疏松症相关的骨折的比例 (即骨质疏松症归因概率)，包括由三个年龄组 (45-64岁，65-84岁，85岁及以上)，三个种族群体 (白人，黑人，所有其他) 和两个性别 (女性，男性)。据估计，在老年白人妇女中，至少90% 的髋部和脊柱骨折应归因于骨质疏松症。其他骨折的比例要小得多，这归因于骨质疏松症。无论骨折类型如何，男性的归因概率低于女性，非白人的归因概率通常低于白人。这些概率将用于估算美国与骨质疏松症相关的骨折相关的总直接医疗费用。

BACKGROUND & AIMS: :Combining the measurement of bone mineral density (BMD) and the classification of the trabecular structure in cancellous bone improves the estimation of the degree of osteoporosis. A fractal method for the automatic quantitative classification of the trabecular structure in midvertebral slices of lumbar vertebrae is introduced. This method is based on the computation of the fractal dimension (box counting method) for varying binarization thresholds. Radiographic images from 30 lumbar vertebrae and CT images from an additional 16 lumbar vertebrae were analysed by calculating the dimension D in dependency of the threshold value T. The function D(T) was normalized by the average image grey value, eliminating the bone mineral density from the computations. The results show that the images of the lumbar vertebrae have fractal properties, and the function D(T) has a typical behaviour that allows the discrimination of the degree of osteoporosis. With two parameters extracted from the function D(T) the correlation coefficients with BMD were both -79% for the radiographic images, and -93% and -91% for the CT data, respectively.

背景与目标： : 结合骨密度 (BMD) 的测量和松质骨中小梁结构的分类，可以改善对骨质疏松症程度的估计。介绍了一种用于腰椎中段椎板小梁结构自动定量分类的分形方法。此方法基于分形维数 (盒计数法) 的计算来改变二值化阈值。通过根据阈值T计算尺寸D来分析来自30个腰椎的放射线图像和来自另外16个腰椎的CT图像。函数D(T) 通过平均图像灰度值进行归一化，从而从计算中消除了骨矿物质密度。结果表明，腰椎图像具有分形特性，函数D(T) 具有典型的行为，可以区分骨质疏松症的程度。利用从函数D(T) 中提取的两个参数，射线照相图像与BMD的相关系数分别为-79%，CT数据与-93% 和-91%。

BACKGROUND & AIMS: OBJECTIVE:The aim of the study was to investigate the impact of hormone therapy (HT) on the ocular surface and intraocular pressure in postmenopausal women. METHODS:This systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement. PubMed, EMBASE, Cochrane Library of Systematic Reviews, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure were searched from inception to November 2019 without language restrictions. Only randomized controlled trials that evaluated the impact of HT on the ocular surface and intraocular pressure in postmenopausal women were eligible. The trials had to report at least one of the following outcomes: break-up time, Schirmer test, corneal staining, ocular surface symptom score, and intraocular pressure. Two investigators independently extracted the information, assessed the risk of bias, and evaluated the publication bias. All data were analyzed by Review Manager V.5.3. Sensitivity analysis and subgroup analysis were performed to find the source of heterogeneity and evaluate the different effects among subgroups. RESULTS:Nine randomized controlled trials (N = 612) were included. The HT group showed significant improvements compared with the control group in break-up time (mean difference [MD] = 2.09, 95% confidence interval [CI] 1.00-3.19, P = 0.0002), Schirmer test without anesthesia (MD = 4.17, 95% CI 1.55-6.80, P = 0.002), Schirmer test with anesthesia (MD = 1.44, 95% CI 0.71-2.18, P = 0.0001), and corneal staining scores (standardized mean difference [SMD] = -0.85, 95% CI -1.39 to -0.30, P = 0.002). Moreover, significant beneficial effects were observed on all four symptoms, including dryness (SMD = -1.21, 95% CI -1.99 to -0.44, P = 0.002), foreign body sensation (SMD = -1.02, 95% CI -1.29 to -0.76, P < 0.00001), ocular fatigue (SMD = -1.74, 95% CI -2.12 to -1.36, P < 0.00001), and burning (SMD = -0.53, 95% CI -0.78 to -0.29, P < 0.0001) after HT. Subgroup analysis revealed that, in terms of break-up time, postmenopausal women younger than 55 years achieved more improvements (MD = 0.88, 95% CI 0.16-1.59, P = 0.02) than women older than 55 years old (MD = 2.60, 95% CI -1.34 to 6.55, P = 0.20), and the estrogen subgroup received more benefits (MD = 3.11, 95% CI 0.93-5.30, P = 0.005) than the estrogen plus progestogen subgroup (MD = 0.42, 95% CI -0.02 to 0.85, P = 0.06). Sensitivity analysis and subgroup analysis suggested that the heterogeneity might derive from the methodological quality, the age of participants, and the intervention of the control group. Intraocular pressure (MD = -1.54, 95% CI -3.39 to 0.32, P = 0.10) was not evidently decreased after HT. No more specific adverse events (relative risk  = 1.66, 95% CI 0.41-6.77, P = 0.48) were found in the HT group. CONCLUSIONS:Our study revealed that HT could improve ocular surface function in postmenopausal women effectively and safely, especially for those who were younger than 55 years, and estrogen only showed more improvements than estrogen plus progestogen. The effectiveness of HT in treating dry eye in postmenopausal women is, however, still a controversial topic. In addition, we did not find HT led to a significant reduction of intraocular pressure.

背景与目标：

BACKGROUND & AIMS: :The transcription factors Runx2 and estrogen receptor-alpha (ERalpha) are involved in numerous normal and disease processes, including postmenopausal osteoporosis and breast cancer. Using indirect immunofluorescence microscopy and pull-down techniques, we found them to colocalize and form complexes in a ligand-dependent manner. Estradiol-bound ERalpha strongly interacted with Runx2 directly through its DNA-binding domain and only indirectly through its N-terminal and ligand-binding domains. Runx2's amino acids 417-514, encompassing activation domain 3 and the nuclear matrix targeting sequence, were sufficient for interaction with ERalpha's DNA-binding domain. As a consequence of the interaction, Runx2's transcriptional activation activity was strongly repressed, as shown by reporter assays in COS7 cells, breast cancer cells, and late-stage MC3T3-E1 osteoblast cultures. Metaanalysis of gene expression in 779 breast cancer biopsies indicated negative correlation between the expression of ERalpha and Runx2 target genes. Selective ER modulators (SERM) induced ERalpha-Runx2 interactions but led to various functional outcomes. The regulation of Runx2 by ERalpha may play key roles in osteoblast and breast epithelial cell growth and differentiation; hence, modulation of Runx2 by native and synthetic ERalpha ligands offers new avenues in selective ER modulator evaluation and development.

背景与目标： : 转录因子Runx2和雌激素受体 α (ERalpha) 参与许多正常和疾病过程，包括绝经后骨质疏松症和乳腺癌。使用间接免疫荧光显微镜和下拉技术，我们发现它们以配体依赖性方式共定位并形成复合物。雌二醇结合的ERalpha直接通过其DNA结合结构域与Runx2强烈相互作用，仅通过其N端和配体结合结构域间接相互作用。Runx2的氨基酸417-514，包括活化结构域3和核基质靶向序列，足以与ERalpha的DNA结合结构域相互作用。作为相互作用的结果，Runx2的转录激活活性被强烈抑制，如COS7细胞，乳腺癌细胞和晚期MC3T3-E1成骨细胞培养物中的报告分析所示。对779乳腺癌活检组织中基因表达的荟萃分析表明，ERalpha和Runx2靶基因的表达呈负相关。选择性ER调节剂 (SERM) 诱导ERalpha-Runx2相互作用，但导致各种功能结果。ERalpha对Runx2的调节可能在成骨细胞和乳腺上皮细胞的生长和分化中起关键作用; 因此，天然和合成的ERalpha配体对Runx2的调节为选择性ER调节剂的评估和开发提供了新的途径。

BACKGROUND & AIMS: :Background Warfarin, a vitamin K antagonist, has been shown to affect bone mineral density and cause osteoporosis. However, studies investigating the relationship between non-vitamin K antagonist oral anticoagulants (NOACs) and osteoporosis are limited. We thus compared the risk of osteoporosis in patients with atrial fibrillation treated with either NOACs or warfarin. Methods and Results This nationwide, retrospective cohort study used Taiwan's National Health Insurance Research Database. All adult patients in Taiwan who were newly diagnosed with atrial fibrillation and treated with NOACs or warfarin between January 2012 and December 2015 were included and classified into their respective cohorts. Patients who received NOACs were subcategorized into the rivaroxaban, dabigatran, and apixaban subgroups. Propensity score matching was performed for each head-to-head comparison. Adjusted hazard ratios (aHRs) for the risk of osteoporosis were calculated using Cox proportional hazards regression models, with adjustment for confounders. Overall, 17 008 patients were included, with 8504 in each cohort. NOACs were associated with a lower osteoporosis risk than warfarin (aHR=0.82; 95% CI=0.68-0.97). A subgroup effect of treatment duration was identified (namely, the lower osteoporosis risk with NOAC compared with warfarin became stronger in those with longer treatment duration [P for interaction <0.001]). Furthermore, significantly lower risks of osteoporosis were observed in the rivaroxaban (aHR=0.68; 95% CI=0.55-0.83) and apixaban (aHR=0.38; 95% CI=0.22-0.66) subgroups, but not in the dabigatran subgroup (aHR=1.04; 95% CI=0.85-1.27). Conclusions Compared with warfarin, rivaroxaban and apixaban were associated with a significantly lower risk of osteoporosis in patients with atrial fibrillation.

背景与目标： 背景: 华法林是一种维生素k拮抗剂，已被证明会影响骨矿物质密度并引起骨质疏松症。然而，研究非维生素k拮抗剂口服抗凝剂 (NOACs) 与骨质疏松症之间关系的研究有限。因此，我们比较了使用NOACs或华法林治疗的房颤患者的骨质疏松症风险。方法和结果这项全国性的回顾性队列研究使用了台湾的国民健康保险研究数据库。纳入了台湾所有新诊断为房颤并在2012年1月和2015年12月之间接受NOACs或华法林治疗的成年患者，并将其分类为各自的队列。接受NOACs的患者分为利伐沙班，达比加群和阿哌沙班亚组。对每次头对头比较进行倾向评分匹配。使用Cox比例风险回归模型计算骨质疏松症风险的校正风险比 (aHRs)，并对混杂因素进行校正。总体而言，包括17 008名患者，每个队列中有8504名。与华法林相比，NOACs与更低的骨质疏松症风险相关 (aHR = 0.82; 95% CI = 0.68-0.97)。确定了治疗持续时间的亚组效应 (即，在治疗持续时间较长的患者中，与华法林相比，NOAC降低的骨质疏松症风险变得更强 [相互作用P <0.001])。此外，在利伐沙班 (aHR = 0.68; 95% CI = 0.55-0.83) 和阿哌沙班 (aHR = 0.38; 95% CI = 0.22-0.66) 亚组中观察到明显更低的骨质疏松症风险，但在达比加群亚组中没有观察到 (aHR = 1.04; 95% CI = 0.85-1.27)。结论与华法林相比，利伐沙班和阿哌沙班与房颤患者发生骨质疏松的风险显著降低相关。

BACKGROUND & AIMS: :Strontium (Sr)-doped calcium sulfate hemihydrate (SrCSH) bioactive materials have been demonstrated to promote osteoporotic bone repair, being associated with the stimulation of bone formation and a reduction in bone resorption. However, the rapid degradation and absorption of SrCSH affects its clinical value. In order to delay the degradation time of SrCSH and improve the utilization of Sr2+, chitosan (CS)-coated SrCSH microspheres (CS-SrCSH) are prepared by electrostatic interaction between CS and SrCSH. X-ray diffraction analysis verifies that SrCSH coated by CS does not alter the phase composition of the SrCSH. It was observed that CS-SrCSH microspheres have uniform particle size. More importantly, the in vivo and in vitro degradation time of CS-SrCSH microspheres is significantly longer than that of SrCSH, and the release rate of Sr2+ is stable, achieving a sustained release effect. Furthermore, CS-SrCSH-based cement is used to repair critical-sized OVX rat tibial defects. The in vivo results reveal that CS-SrCSH exhibits a long-term capability for osteogenesis, angiogenesis and bone metabolism inhibition. In conclusion, the controllable degradation of CS-SrCSH-based cements described here could be beneficial for the repair of bone defects, especially in the osteoporotic bone.

背景与目标： : 掺锶 (Sr) 的半水硫酸钙 (SrCSH) 生物活性材料已被证明可促进骨质疏松的骨修复，与刺激骨形成和减少骨吸收有关。然而，SrCSH的快速降解和吸收影响了其临床价值。为了延缓SrCSH的降解时间并提高Sr2的利用率，通过CS和SrCSH之间的静电相互作用制备了壳聚糖 (CS) 包覆的SrCSH微球 (CS-SrCSH)。X射线衍射分析验证了用CS涂覆的SrCSH不会改变SrCSH的相组成。观察到CS-SrCSH微球具有均匀的粒径。更重要的是，cs-srcsh微球的体内外降解时间明显长于SrCSH，且Sr2 + 的释放速率稳定，达到了缓释效果。此外，基于cs-srcsh的水泥用于修复临界尺寸的OVX大鼠胫骨缺损。体内结果表明，cs-srcsh具有长期的成骨，血管生成和骨代谢抑制能力。总之，本文所述的基于cs-srcsh的水泥的可控降解可能有利于骨缺损的修复，尤其是在骨质疏松的骨中。

BACKGROUND & AIMS: :Osteoporosis is an important skeletal disease characterized by bone weakness and high risk of fracture in postmenopausal women. Tea consumption is known to play an important role in the prevention or alleviation of osteoporosis. However, the therapeutic effects of aqueous extracts of white tea (WT) have not been evaluated in osteoporosis rat models. The aim of this study was to investigate the potential anti-osteoporotic role of WT in ovariectomized (OVX) rats. WT was given orally at 0.5% w/v doses for 12 weeks in OVX rats. Biochemical parameters in blood samples, bone tartrate-resistant acid phosphatase (TRAP), C-terminal telopeptide of type 1 collagen (CTX) and estradiol levels were evaluated. Bone mineral density and bone mineral content values were measured in the left femur. In addition to histopathological examination, osteolcalcin, osteopontin and TUNEL levels were determined. OVX group data demonstrated that bone loss occurred by thinning of the metaphyseal growth plates of the femur. Similarly, the levels of TRAP and CTX, markers of osteoclastic activity, were found to be high concurrently with a decrease in femoral bone mineral density. In addition, increased osteolcalcin and osteopontin levels were present in the metaphyseal growth zones. On the other hand, while TRAP and CTX levels were suppressed in the OVX-WT group, bone mineral content increased. In ad-dition, TUNEL, osteocalcin and osteopontin positivity decreased in the right femoral metaphysis growth zones, proliferating zone and resting zone cells. These results showed that chronic WT consumption has a protective effect by reducing bone resorption in OVX-induced osteoporotic rats.

背景与目标： : 骨质疏松症是一种重要的骨骼疾病，其特征是绝经后妇女的骨骼无力和高骨折风险。众所周知，饮茶在预防或减轻骨质疏松症中起着重要作用。然而，尚未在骨质疏松症大鼠模型中评估白茶 (WT) 水提取物的治疗作用。这项研究的目的是研究WT在去卵巢 (OVX) 大鼠中的潜在抗骨质疏松作用。在OVX大鼠中以0.5% w/v剂量口服WT 12周。评估血液样本中的生化参数，抗骨酒石酸酸性磷酸酶 (TRAP)，1型胶原蛋白的C末端肽 (CTX) 和雌二醇水平。测量左股骨的骨矿物质密度和骨矿物质含量值。除组织病理学检查外，还确定了骨钙素，骨桥蛋白和TUNEL水平。OVX组数据表明，股骨干phy端生长板变薄会导致骨质流失。同样，发现破骨细胞活性标志物TRAP和CTX的水平很高，同时股骨骨矿物质密度降低。此外，在干phy端生长区域中存在骨钙素和骨桥蛋白水平升高。另一方面，尽管OVX-WT组的TRAP和CTX水平受到抑制，但骨矿物质含量增加。另外，TUNEL，骨钙素和骨桥蛋白阳性在右股骨干端生长区，增殖区和静息区细胞中降低。这些结果表明，长期消耗WT通过减少OVX诱导的骨质疏松大鼠的骨吸收而具有保护作用。