EFFECT OF CALCIUM & VITAMIN D ON BONE LOSS FROM HIP--ROLE OF INTERLEUKIN 6

在成人中，生长因子及其结合蛋白影响骨形成，细胞因子IL-6促进破骨细胞募集和骨吸收。我们的STOP/IT继续研究的主要目的是确定补充钙和维生素D是否会改变循环中IGF-1、IGFBP-4和IL-6的水平，如果是这样，这些化合物的循环水平的变化是否与补充对骨质流失率的有益影响有关。本研究验证了以下假设：通过降低循环中甲状旁腺激素（PTH）和1,25-二羟基维生素D （1,25(OH)2D）的水平，补充钙和维生素D将a)降低IGFBP-4药物对IGF-1诱导的骨形成的抑制作用，b)降低IL-6诱导的骨吸收。在塔夫茨大学，389名65岁以上的成年人（172名男性和273名女性）最近完成了一项为期3年的随机双盲对照试验，旨在确定补充钙和维生素D是否能降低全身、髋关节和脊柱的骨质流失率。受试者每天服用500毫克钙加700国际单位维生素D或安慰剂。骨密度、钙调节激素水平和其他生化指标均被跟踪。在试验期间，补充剂显著降低了PTH和125 (OH)2D的循环水平，并降低了每个骨骼部位的骨质损失率。拟议的研究包括分析在基线和治疗IGF-1、IGFBP-4和IL-6三年后收集的存档的Tufts STOP/IT样本。随着这些测量的增加，STOP/IT数据集将为探索钙和维生素D摄入量变化影响骨质流失率的潜在机制提供丰富的机会。

In adults, growth factors and their binding proteins influence bone formation, and the cytokine IL-6 promotes osteoclast recruitment and bone resorption. The primary aims of this proposed supplement to our STOP/IT continuation study are to determine whether supplementation with calcium and vitamin D changes circulating levels of IGF-1, IGFBP-4, and IL-6 and, if so, whether changes in circulating levels of these compounds are associated with the beneficial effect of supplementation on rates of bone loss. This study tests the hypothesis that supplemental calcium and vitamin D, by lowering circulating levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D (1,25(OH)2D), will a) decrease the IGFBP-4 medicated inhibition of IGF-1 induced bone formation and b) decrease IL-6 induced bone resorption. At Tufts, 389 adults over age 65 (172 men and 273 women) recently completed a 3-year, randomized, double-blind controlled trial designed to determine whether calcium and vitamin D supplementation reduced rates of bone loss from the total body, hip, and spine. Subjects received either 500mg of calcium plus 700 IU of vitamin D or placebo daily. Bone mineral density and calcium regulating hormone levels and other biochemistries were followed. During the trial, supplementation significantly lowered circulating levels of PTH and 1,25(OH)2D and reduced rates of bone loss from each skeletal site. The proposed study involves assaying archived Tufts STOP/IT samples collected at baseline and after three years of treatment for IGF-1, IGFBP-4, and IL-6. With the addition of these measurements, the STOP/IT data set would offer an enriched opportunity to explore potential mechanisms by which changes in calcium and vitamin D intake influence rates of bone loss.