GENETIC AND HORMONAL INFLUENCES ON BONE DENSITY

遗传和激素对骨密度的影响

• 批准号: 6162217
• 负责人: GLINDA S COOPER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6162217
• 关键词: bone density; bone metabolism; clinical chemistry; clinical research; female; genetic polymorphism; genetic regulation; genotype; hormone regulation /control mechanism; human middle age (35-64); human subject; longitudinal human study; menopause; nutrition related tag; vitamin D receptors

Summary of Work: We examined the influence of vitamin D receptor (VDR) polymorphisms on bone mineral density (BMD), rate of change in BMD, and markers of bone metabolism in a longitudinal study during the perimenopausal years. The study included 103 women ages 40 to 54 years at baseline, followed from 1987 to 1995. BMDs at the hip, radius, and spine were measured at approximately 2 year intervals. Fasting blood and first void urine samples were obtained at the last BMD assessment and were used to determine VDR genotype and levels of 1,25(OH)2D, 25(OH)D , osteocalcin, bone-specific alkaline phosphatase (alkphos), and type I collagen products: N-telopeptide cross-linking domain (NTx) and free deoxypyridnoline (Dpyr). The mean age was 46.4 years at baseline. The rate of decline in BMD was significantly steeper among post-menopausal women at the spine (mean difference, post- vs pre-menopause, -2.1%/year), hip (-1.6%/year), and mid-radius (-1.5%/year) (p< 0.01), and there was a trend toward higher levels of the markers of bone formation and resorption. Controlling for age and menopausal status,spinal BMD at baseline was 4.6% lower in the tt genotype compared to the TT genotype (p=0.27); the difference at the distal radius was - 1.4% (p=0.79), at the mid radius, - 3.2% (p=0.16), and at the hip, + 1.7% (p=0.16). The differences between genotype in rate of decline were not statistically significant, but the steepest rate of decline was seen in the TT genotype at the spine, mid radius, and hip. There were no consistent differences by genotype in vitamin D metabolites or bone metabolism markers. Our results are consistent with a small effect (3-4%) of VDR genotype on pre- menopausal spine and mid-radius BMD, but with our sample size, these effects were not statistically significant.

工作摘要：我们检查了维生素D受体（VDR）的影响 骨矿物质密度（BMD）的多态性，BMD的变化率和 在一项纵向研究中，骨代谢的标志 绝经年份。该研究包括103名40至54岁的女性 基线，随后是1987年至1995年。臀部，半径和脊柱的BMD 以大约2年的间隔测量。 禁食和首先 在最后一次BMD评估中获得了空隙尿液样品，并使用 确定VDR基因型和1,25（OH）2d，25（oh）d的水平， 骨钙素，骨特异性碱性磷酸酶（烷烃）和I型 胶原蛋白产品：N-甲基肽交联域（NTX）和游离 Deoxypyridnoline（DPYR）。基线时的平均年龄为46.4岁。这 绝经后，BMD的下降率明显更高 脊柱的妇女（平均差异，在少年前与 - 每年-2.1％）， 臀部（-1.6％/年）和Mid-Radius（-1.5％/年）（p <0.01），并且有一个 向更高水平的骨骼形成标记的趋势和 吸收。控制年龄和绝经状态，脊柱BMD 与TT基因型相比，TT基因型的基线低4.6％ （p = 0.27）;远端半径的差异为-1.4％（p = 0.79），在 中半径为-3.2％（p = 0.16），在臀部 + 1.7％（p = 0.16）。这 基因型下降率之间的差异在统计上不是 显着，但在TT基因型中观察到最急剧的下降速度 在脊柱，中半径和臀部。 没有一致的差异 通过维生素D代谢产物或骨代谢标记的基因型。我们的 结果与VDR基因型的影响很小（3-4％）一致。 更年期的脊柱和中radius BMD，但有了我们的样本量 影响在统计学上没有意义。