Relations between interleukin-1, its receptor antagonist gene polymorphism, and bone mineral density in postmenopausal Korean women

We investigated the relation between polymorphisms in the interleukin-1(IL-1) and IL-1 receptor antagonist (IL-1ra) gene, and bone mineral density (BMD) in postmenopausal Korean women. The IL-1α C⁻⁸⁸⁹T polymorphism, and IL-1β C⁻⁵¹¹T polymorphism were examined by restriction fragment length polymorphism, and 86-bp variable number tandem repeat polymorphism in the IL-1ra gene was analyzed by the polymerase chain reaction and electrophoresis in 202 postmenopausal Korean women. Serum osteocalcin, and C-telopeptide of type I collagen were measured using a radioimmunoassay and enzyme-linked immunosorbent assay, respectively. BMD at the lumbar spine and proximal femur was measured by dual-energy X-ray absorptiometer. No significant differences in BMD or in serum bone markers levels were noted across the IL-1α or IL-1β genotype. There were no significant differences in the distribution of IL-1α or IL-1β genotype according to the status of bone mass. BMD in women carrying the A2 allele of the IL-1ra gene was significantly lower than those without this allele, and the A2 allele was more frequent in osteoporotic women than in normal women. These data suggest that IL-1ra gene VNTR polymorphism is a genetic factor that may affect BMD in Korean women.     

Lack of association between interleukin-1 receptor antagonist protein gene polymorphism and bone mineral density in Hungarian postmenopausal women

The major determinant for risk of osteoporosis in later life is bone mineral density (BMD) attained during early adulthood. Bone mineral density is a complex trait that is presumably influenced by multiple genes. Interleukin-1 receptor antagonist protein (IL-1RN) is an attractive candidate gene for osteoporosis susceptibility, because IL-1RN completely inhibits the stimulatory effects of interleukin-1 (IL-1) on bone resorption in organ cultures and has been implicated in the pathogenesis of osteoporosis. In addition, the IL-1RN gene contains a variable-number tandem repeat polymorphism (VNTR) in intron 2 with three potential protein-binding sites. Recently, an association has been found between this polymorphism and postmenopausal bone loss in the spine. In this study, we use the previously described IL-1RN polymorphism to test for an association between this polymorphism and bone mineral density in our population of postmenopausal women. There was no correlation between alleles or genotypes and BMD in the 286 subjects. Dividing subjects into osteoporotic and healthy groups (osteoporotics and controls), we found no difference in the distribution of alleles or genotypes between groups. We found no association between IL-1RN alleles or genotypes and BMD either at the lumbar spine or the femoral neck within groups. Our data do not support the hypothesis that this IL-1RN gene VNTR polymorphism has an impact on bone mass in postmenopausal women.     

Vitamin D status in relation to obesity, bone mineral density, bone turnover markers and vitamin D receptor genotypes in healthy Saudi pre- and postmenopausal women

Summary

The various factors that may contribute to vitamin D deficiency or insufficiency were examined among healthy Saudi pre- and postmenopausal women. Vitamin D deficiency was highly prevalent among studied Saudi women with obesity, poor sunlight exposure, poor dietary vitamin D supplementation and age as the main risk factors.

Introduction

The various factors that may contribute to vitamin D deficiency or insufficiency in relation to bone health among Saudi women are not known. The main objectives of the present study were to determine the factors influencing vitamin D status in relation to serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH), bone turnover markers (BTMs), bone mineral density (BMD), and vitamin D receptor genotype (VDR) in healthy Saudi pre- and postmenopausal women.

Methods

A total number of 1,172 healthy Saudi women living in the Jeddah area were randomly selected and studied. Anthropometric parameters, socioeconomic status, sun exposure index together with serum levels of 25(OH)D, calcitriol, intact PTH, Ca, PO4, Mg, creatinine, albumin, and biochemical BTMs were measured. BMD was measured by a dual energy X-ray absorptiometry and VDR genotypes were also determined.

Results

About 80.0% of Saudi women studied exhibited vitamin D deficiency (serum 25(OH)D?<?50.0?nmol/L) with only 11.8% of all women were considered with adequate vitamin D status (serum 25(OH)D?>?75?nmol/L). Secondary hyperparathyroidism was evident in 18.5% and 24.6% in pre- and postmenopausal women with 25(OH)D?<?50?nmol/L. Serum 25(OH)D was lower (P?<?0.001) and intact PTH higher (P?<?0.001) in the upper quintiles of body mass index (BMI) and waist-to-hip ratio (WHR). Multiple linear regression analysis showed that BMI, sun exposure index, poor dietary vitamin D supplementation, WHR, and age were independent positive predictors of serum 25(OH)D values.

Conclusions

Vitamin D deficiency is highly prevalent among healthy Saudi pre-and postmenopausal women and largely attributed to obesity, poor exposure to sunlight, poor dietary vitamin D supplementation, and age.     

Dietary habit and bone mineral density in Korean postmenopausal women

Summary  

Postmenopausal women were assessed to determine the association between dietary intake of various food groups and low bone mineral density. Among dietary factors, high consumption of protein-containing food and dairy products was associated with a reduced risk for low bone mineral density.     

白介素1受体措抗剂基因多态性与上海市绝经后妇女骨密度无相关性

目的 了解白介素1受体拮抗剂（IL-1RA）基因多态性与绝经后妇女骨密度（BMD）的关系.方法 筛选370名年龄47～75岁无血缘关系的上海市汉族绝经后妇女,双能X线吸收仪检测腰椎2～4和近端股骨包括股骨颈、大转子和Ward＇s三角的BMD,按BMD值分为152例骨质疏松患者和218例对照组.IL-1RA基因型检测通过聚合酶链反应和电泳鉴定.结果 在整个人群中,IL-1RA等位基因的频率分布是A1占94.3%,A2占4.6%和A4占1.1%,等位基因频率分布符合Hardy-Weinberg定律.在骨质疏松组和对照组中IL-1RA等位基因A2型频率分布差异无显著性（x2=3.30,P=0.069）.无论是在整个人群还是各亚组中,均未发现IL-1RA基因多态性与各部位BMD有相关性.结论 本研究显示IL-1RA的基因型和等位基因频率分布与高加索人群有显著差别,IL-1RA基因多态性可能不是影响上海市绝经后妇女BMD变异或骨质疏松的遗传因子.     

安徽地区绝经后妇女雌激素受体基因多态性与骨密度的相关性研究

目的探讨安徽地区绝经后妇女雌激素受体（ER）基因多态性的分布及其与骨密度的相关性。方法随机选择288名安徽合肥地区健康绝经后妇女，运用双能X线骨密度吸收法（DEXA）测定腰椎和股骨颈、大转子骨密度（BMD），并采用PCR-RFLP（聚合酶链反应-限制性片断长度多态性）法分析ER基因多态性，并分析其相关性。结果安徽地区绝经后妇女ER基因型分布频率PP（13．2％）、Pp（45．8％）、pp（40．9％），XX（5．21％）、Xx（31．6％）、xx（63．2％），联合PvuⅡ和XbaⅠ这两种基因型后得到：PPXX（5．6％），PPXx（3．8％），PPxx（6．3％），PpXX（1．4％），PpXx（23．3％），Ppxx（25％），ppxx（34．7％），未检测到ppXX及ppXx型。PvuⅡ多态性与绝经后妇女腰椎BMD相关，PP基因型腰椎BMD显著低于pp和Pp基因型（P〈0．05），ER基因P等位基因是一种有益于骨量的基因型。XbaⅠ多态性与绝经后妇女各部位BMD间无明显相关性（P〉0．05）。联合分析PvuⅡ和XbaⅠ多态性与绝经后妇女BMD相关性发现，有Px单倍型的妇女腰椎部位的BMD显著低于无此单倍型的妇女（P〈0．01）。结论ER基因PVuⅡ多态性与绝经后妇女腰椎BMD有相关性，PP基因型妇女腰椎BMD减低，而具有Px单倍型的ER基因可能对BMD有不利影响。     

Association of SMAD2 polymorphisms with bone mineral density in postmenopausal Korean women

Summary

In a candidate gene association study, we found that SMAD2 promoter alleles and haplotypes were significantly associated with bone mineral density (BMD) at the lumbar spine and various proximal femur sites. Our results suggest that SMAD2 polymorphisms may be one of genetic determinants of BMD in postmenopausal women.

Introduction

SMAD2, which is the specific intracellular transducer of TGF-?, is thought to participate in bone metabolism by playing a critical role in the development and function of osteoclasts and osteoblasts. We performed association analyses of the genetic variation in SMAD2 to ascertain the contribution of this gene to BMD and risk of osteoporotic fracture.

Methods

We selected three SMAD2 promoter single-nucleotide polymorphisms (SNPs) based on heterozygosity and validation status. Postmenopausal Korean women (n?=?1,329) were genotyped for these SNPs, and their BMD and risk of fractures were assessed. BMD at the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry. P values were corrected for multiple testing by the effective number of independent marker loci (P ^cor).

Results

We found that SMAD2 -35302C>T, -34952A>G, and ht2 were significantly associated with BMD at both the lumbar spine and femur neck (P ^cor?=?0.020?C0.046), whereas SMAD2 -36201A>G and ht1 affected the femur neck BMD (P ^cor?=?0.018?C0.031). The genetic effects of these three polymorphisms on BMD at the lumbar spine and femur neck were risk-allele dependent in additive model. The three polymorphisms and two hts were also significantly associated with BMD at other proximal femur sites, such as the total femur, trochanter, and femur shaft (P ^cor?=?0.001?C0.046). However, none of the polymorphisms or hts was associated with an increased risk of fracture.

Conclusions

Our results suggest that SMAD2 polymorphisms may be one of genetic determinants of BMD in postmenopausal women.     

Association of estrogen receptor alpha and collagen type I alpha 1 gene polymorphisms with bone mineral density in postmenopausal women

Summary  

In this study, ERα gene PvuII and XbaI polymorphisms and COL1A1 gene Sp1 polymorphisms in postmenopausal women were compared with lumbar vertebra and femoral neck BMD values. In conclusion, it was designated that PvuII polymorphism was effective on average lumbar vertebra BMD value in postmenopausal women of our study group.     

Effects of bazedoxifene on bone mineral density,bone turnover,and safety in postmenopausal japanese women with osteoporosis

This randomized, double‐blind, placebo‐controlled, dose‐response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (?0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo (p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks (p < .05 for all) and were sustained throughout the study. Total and low‐density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo (p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis. © 2011 American Society for Bone and Mineral Research.     

老年男性骨密度与白介素-1受体拮抗剂及有关生化指标关系的研究

目的 探讨白介素－1及其受体拮抗剂在老年男性骨代谢中的作用。方法 老年男性组133例，老年前期男性组35例。酶联免疫法（ELISA）测定血浆白介素－1β（IL－1β）、IL－1受体拮抗剂（IL－1Ra)、血清骨钙素（BGP）、尿I型胶原C末端肽（CTX）。放免法叫雌二醇（E2）、总睾酮（T）。结果 与老年前期男性相比，老年男性组L2－4、股骨颈、大转子的骨密度、E2、T、IL－1Ra/IL-1比值、BGP较低，而CTX较高，差异有显性，L2－4、股骨颈、Ward's骨密度、BGP与IL－1Ra/IL-1β呈正相关。CTX与IL－1Ra/IL-1β负相关、与IL－1β正相关。L2－4、大转子的骨密度、BGP与E2正相关；股骨颈、大转子骨密度、BGP与T正相关。IL－1Ra、IL－1Ra/IL-1β与E2正相关（P＜0．05）。结论 老年男性骨代谢处于高分解、低合成的负平衡状态，骨密度低于老年前期的男性，性激素降低影响IL－1Ra、IL－1两的平衡的可能起重要作用。     

Long-term estrogen replacement therapy in postmenopausal women sustains vertebral bone mineral density

The cross-sectional relationship between long-term estrogen use and vertebral (L2-4) bone mineral density (BMD) was determined in 65 postmenopausal white women between 55 and 75 years who were at least 10 years from their menopause. Long-term estrogen users began therapy within 5 years of menopause and continued for a duration of at least 10 years. The mean duration of use was 19.8 years. Controls used estrogen for less than 1 year. There was a significant difference (p less than 0.02) in mean spinal BMD between estrogen users (1.219 g/cm2) and controls (1.092 g/cm2). There was no significant difference in age, height, weight, or dietary calcium (Ca) intake between the two groups. The statistical difference in BMD was retained when (1) 23 estrogen users were paired with age-matched controls, (2) only women with a natural menopause or history of bilateral oophorectomy were included, and (3) only women with a natural menopause were compared. A spinal BMD below the estimated fracture threshold of 0.965 g/cm2 was found in 11 of 40 controls and only 2 of 25 estrogen users. Comparison of estrogen users with a natural menopause to those with bilateral oophorectomy revealed no significant difference in BMD. These data confirm the salutary effect of long-term estrogen use in the maintenance of vertebral bone mass in postmenopausal women.     

Associations of vitamin D status with bone mineral density, bone turnover, bone loss and fracture risk in healthy postmenopausal women. The OFELY study

INTRODUCTION: Vitamin D status is considered as an important determinant of bone health but supplementation trials with vitamin D(3) have yielded conflicting results. The aim of this study was to investigate the associations between serum 25-hydroxyvitamin D (25-OH D), bone turnover markers, bone mineral density (BMD), radius bone loss and incidence of fracture in postmenopausal women. METHODS: 669 postmenopausal women (mean age: 62.2 years) belonging to a population-based cohort were followed prospectively for a median of 11.2 years. At baseline, 25-OH D levels, BMD, bone turnover markers and clinical risk factors of osteoporosis were assessed. BMD loss at the radius was estimated by annual measurements of BMD and all incident fractures which occurred in 134 women were confirmed by radiographs. RESULTS: 73% and 35% of women had serum 25-OH D levels below 75 and 50 nmol/l which correspond respectively to the median and lowest optimal values recently proposed for fracture prevention. 11% of women had levels below 30 nmol/l. Serum 25-OH D correlated modestly with intact PTH (r(2)=0.023, p<0.0001), but not with bone turnover markers or BMD at the hip and radius after adjustment for age. When levels of 25-OH D were considered as a continuous variable, there was no significant association between 25-OH D levels and radius BMD loss or fracture risk. After adjustment for age, there was no significant difference in incidence of fracture, BMD, radius BMD loss, bone turnover markers, grip strength and the percentage of fallers in the previous year between women with 25-OH D levels below or above 75, 50 or 30 nmol/l. CONCLUSIONS: In a population of home-dwelling healthy postmenopausal women with few of them with severe vitamin D deficiency, vitamin D status may not be an important determinant of bone health.     

广西壮、汉族绝经后妇女维生素D受体基因型与骨密度的关系

目的 探讨维生素D受体基因(VDR)型在广西壮、汉族绝经后妇女中的分布及其与骨密度(BMD)的关系。方法 在广西居住20年以上、无血缘关系的健康绝经后妇女198名,其中三代均为壮族的116名,均为壮族的82名。记录他们的年龄、绝经年龄,测量他们的身高、体重。用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法测定受试者的VDR基因型;用双能X线吸收法测定髋部、腰椎和前臂的骨密度。结果 壮、汉两组妇女VDR基因型和VDR等位基因频率分布均无显著性差异(P>0.05);198名妇女BB、Bb、bb基因型检出率分别为6.57％、66.16％和27.27％;B、b等位基因分别为39.65％和60.35％。BB基因型组第二腰椎(L2)BMD较bb基因型组低10.03％(P=0.047),第四腰椎(L4)BMD分别较bb、Bb基因型组低9.63％(P=0.043)和12.44％(P=0.005)。BB基因型组骨质疏松发生率最高(46.15％),Bb基因型组次之(19.86％),bb基因型组最低(14.81％),差异有显著性(P=0.04)。结论 VDR基因型与广西壮、汉族绝经后妇女BMD有关联,BB基因型可能可作为预测广西壮、汉族绝经后妇女骨质疏松危险性的遗传学标志之一。     

No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal Danish women

The polymorphisms of the estrogen receptor (ER) gene defined by the restriction enodonucleases PvuII and XbaI have recently been reported to be associated with bone mineral density (BMD) in postmenopausal women. To investigate the possible relation of the PvuII and XbaI restriction fragment-length polymorphisms of the ER gene with BMD in Danish postmenopausal women, two studies were undertaken: 1) a cross-sectional study of 499 postmenopausal women, where the ER genotypes and alleles were related to BMD of the hip, spine, and lower forearm; and 2) a longitudinal study of 101 postmenopausal women followed up for 18 years. In the latter study, late postmenopausal bone loss in the hip and spine was determined over a period of 6 years in women (mean age of 63 to 69 years), and long-term postmenopausal bone loss in the lower forearm was determined over a period of 18 years in women (mean age of 51 to 69 years). Genotyping was performed through the restriction cleavage of polymerase chain reaction-amplified genomic DNA with the two restriction enzymes, PvuII and XbaI. Restriction fragment-length polymorphisms were represented as P or p (PvuII) and X or x (XbaI), with the lower case letters signifying the presence of the restriction site. The frequencies of the ER genotypes were similar to previously published genotype frequencies in Caucasian and Asian populations. No significant effect of the ER genotypes or alleles on BMD was found at any site, nor was there a relation between ER genotypes and the rate of bone loss either in the hip and spine over 6 years, or in the lower forearm over 18 years. In conclusion, we could not demonstrate any major effect of the ER gene polymorphisms on BMD or rate of bone loss in healthy postmenopausal Danish women.     

绝经后妇女血清OPN水平与骨密度及骨转换水平的相关性研究

目的：研究绝经后女性血清骨桥蛋白（OPN）水平与骨密度（BMD）、骨标志物的关系,探索OPN在绝经后骨质疏松症（ PMOP）中的临床应用价值。方法对125名绝经后女性进行研究,双能X线骨密度仪测量腰1－4及左股骨颈BMD,测定血中I型原胶原N－端前肽（PINP）、β－胶原降解产物（β－CTX）、25羟维生素D、甲状旁腺素、OPN、骨钙素（OC）、钙（Ca）和磷（P）。结果①骨质疏松组血清OPN水平明显高于骨量减少和正常组（ F＝0．118,P＝0．000）;②血清OPN水平与BMD（腰1－4,左股骨颈）、血Ca显著负相关,与年龄、β－CTX、OC显著正相关（ P均＜0．05）;③多元线性回归分析结果表明,左股骨颈骨密度（B,－11．971;SE,2．383;标准系数,－0．402;P＝0．000）、血钙（B,－6．696;SE,2．383;标准系数,－0．225;P＝0．006）是OPN水平独立预测因子。结论高血清OPN水平与低BMD、高β－CTX水平及钙缺乏相关,该结果丰富了现有的临床证据,为防治PMOP提供了新的思路。     

绝经后骨质疏松人群雌激素受体基因Xba I多态性和年龄对骨密度的影响

目的 分析绝经后骨质疏松人群雌激素受体(ER)基因XbaⅠ多态性与骨密度的相关性以及在基因多态性下年龄、绝经年限及体重指数(BMI)对骨密度的影响。方法 用双能X线骨密度仪检测患者151例，以PCR-RFLP的方法检测ER基因XbaⅠ多态性，SPSS软件进行相关回归分析。结果 ER基因型的频率分布为XX型16．6％，Xx型67．5％，xx型15．9％，XX型的骨密度在腰椎、股骨颈和Ward’s三角要高于Xs型和xx型。但ER多态性与骨密度无相关性。在Xx型和XX型人群中年龄越大，绝经年限越长，腰椎和股骨上端骨密度则越低。在XX型中，BMI是影响股骨颈和Ward’s三角骨密度的主要因素。而在xx型中，腰椎和ward’s三角骨密度与年龄、BMI和绝经年限无相关性，绝经年限与股骨颈骨密度相关，大转子与BMI相关。结论 福州地区绝经后骨质疏松人群ER基因XbaⅠ基因型与骨密度无明显相关性，但在不同基因型人群中，其骨密度的丢失趋势和影响因素也各异，临床上应采用不同的防治措施。     

绝经妇女骨密度变化与雌激素、生长激素水平的相关关系初探

收集61饲病例，分为生育年龄组13例，绝经前组10例，绝经后组38例，均进行血碱性磷酸酶(ALP)、血钙(Ca)、血磷(P)、雌二醇(E2)、促卵泡素(FSH)、生长激素(GH)及空腹尿钙／尿肌酐(尿Ca／Cr)测定，其中3组进行定量CT测定腰椎骨密度(BMD)，分别为13、7、28例；其中绝经后组中10侧患者服用尼尔雌醇(CEE3)3个月：结果显示绝经后妇女BMD显著下降，其BMD与E2及GH呈正相关．在绝经早期组中BMD与尿Ca／Cr值呈负相关．诨步回归分析显示绝经年限对绝经后妇女BMD影响最大，其次为GH；服CEE3 3个月后血ALP显著下降，尿Ca／Cr显著下降，GH升高。本文提示GH的下降是绝经后骨代谢变化的膨响因素之：CEE，能有效防止绝经后妇女的骨丢失，但长期应用有待进一步的研究。     

Estrogen receptor gene polymorphism and bone mineral density in postmenopausal Chinese women

PvuII and XbaI restriction fragment length polymorphisms (RFLPs) for the estrogen receptor gene (ERG) and its relation to bone mineral density (BMD) were examined in 454 postmenopausal Chinese women, aged 55-79 years. The RFLPs were represented as P or p (PvuII) and X or x (XbaI), with capital letters signifying the absence of and small letters the presence of restriction sites. There was no significant difference in BMD between the PP, Pp, and pp genotypes. However, women of the XX genotype had significantly higher BMD at the spine than women of the Xx or xx genotype. The magnitude of the difference in BMD was 80% of a standard deviation (SD) for BMD in elderly women and 40% of a SD in postmenopausal women. There was no statistically significant interaction between the PvuII genotype and the XbaI genotype in determining BMD. We conclude that postmenopausal Chinese women who were homozygous for the XX genotype had slightly higher BMD than the others. However, the difference in BMD was small and was unlikely to have any clinical significance. The ERG is not a major determinant of BMD in Chinese women in Hong Kong.     

雌激素受体α和维生素D受体基因多态性与哈尔滨地区绝经后妇女骨密度的关系

目的探讨哈尔滨市绝经后妇女雌激素受体α(ER-α)基因和维生素D受体(VDR)基因多态性与骨密度的关系。方法对哈尔滨市81例无亲缘关系汉族健康妇女进行PCR-RFLP测定ER-α基因PvuⅡ、XbaⅠ多态性和VDR基因BSMⅠ多态性,用双能X线吸收法测定骨密度(BMD)。结果本研究人群PP、Pp及pp基因型频率分别为13.6%、49.4%、37.0%;XX、Xx及xx基因型频率各为4.9%、40.7%、54.4%;BB、Bb及bb基因型频率各为0%、16.0%、84.0%,t检验分析各基因型与BMD值的关系显示:绝经后妇女中,雌激素受体基因型仅与腰椎骨密度有显著差异。维生素D受体基因型在股骨颈、大转子部位有显著差异。PvuⅡ多态性和BSMⅠ多态性共同作用对骨密度影响更大。结论雌激素受体、维生素D受体基因型分布频率均符合Hardy-Weinberg定律,并且与骨密度有一定的关联,尤其是基因与基因的共同作用与骨密度的关系更为密切。     

Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy

Patients treated with bisphosphonates for osteoporosis may discontinue or require a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor of bone resorption that has been shown to increase bone mineral density (BMD) and decrease fracture risk in postmenopausal women with osteoporosis. This was a multicenter, international, randomized, double‐blind, double‐dummy study in 504 postmenopausal women ≥ 55 years of age with a BMD T‐score of ?2.0 or less and ?4.0 or more who had been receiving alendronate therapy for at least 6 months. Subjects received open‐label branded alendronate 70 mg once weekly for 1 month and then were randomly assigned to either continued weekly alendronate therapy or subcutaneous denosumab 60 mg every 6 months and were followed for 12 months. Changes in BMD and biochemical markers of bone turnover were evaluated. In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month 12 compared with a 1.05% increase in subjects continuing on alendronate (p < .0001). Significantly greater BMD gains with denosumab compared with alendronate also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius (all p < .0125). Median serum CTX levels remained near baseline in the alendronate group and were significantly decreased versus alendronate (p < .0001) at all time points with denosumab. Adverse events and serious adverse events were balanced between groups. No clinical hypocalcemic adverse events were reported. Transition to denosumab produced greater increases in BMD at all measured skeletal sites and a greater reduction in bone turnover than did continued alendronate with a similar safety profile in both groups. Copyright © 2010 American Society for Bone and Mineral Research