PATHOGENESIS OF OSTEOPOROSIS IN OLDER WOMEN

骨质疏松症是老年妇女的一个主要健康问题。 虽然所有绝经后妇女都是雌激素缺乏，但只有一些发展为骨质疏松症;许多绝经后妇女骨转换率和骨丢失率很高。 我们发现，绝经后老年妇女的骨量和骨转换率有很大的差异，通过血清和尿液生化标志物估计，骨转换率的增加与骨量降低和骨丢失率增加有关。 此外，我们已经表明，雌激素显着抑制骨吸收在这个群体中，雌激素的作用，以减少激活频率，活检标本中骨转换的形态学指标，与骨吸收的生化标志物的基线水平呈负相关。我们计划测试两个相关的假设，细胞因子在骨质疏松症的发病机制中的作用。 第一个是，在老年雌激素缺乏妇女中观察到的骨转换和骨量的变化是由于局部细胞因子产生的差异。 尽管有几种细胞因子与绝经后骨质疏松症有关，但我们将重点关注白细胞介素-1系统，包括白细胞介素-1、白细胞介素-1、白细胞介素-1受体拮抗剂、白细胞介素-1受体1和白细胞介素-1受体2。我们假设老年女性的高骨转换和低骨量与IL-1活性正相关。第二个假设是雌激素调节骨中局部细胞因子的产生，骨中局部细胞因子产生的差异解释了对雌激素反应的变异性。 我们假设，IL-1活性将增加时，雌激素从老年妇女谁是目前的雌激素使用者在基线和IL-1活性将减少时，雌激素重新引入和变化的幅度将与骨转换和骨量的变化。

Osteoporosis is a major health concern for older women. Although all postmenopausal women are estrogen-deficient, only some develop osteoporosis; many postmenopausal women have high rates of bone turnover and bone loss. We have found that older postmenopausal women have a wide range of bone mass and rates of bone turnover and that increased turnover, as estimated by serum and urine biochemical markers, is associated with lower bone mass and greater rates of bone loss. In addition, we have shown that estrogen markedly inhibits bone resorption in this population and that the effect of estrogen to decrease activation frequency, a morphologic indicator of bone turnover in biopsy specimens, is inversely correlated with baseline levels of biochemical markers of bone resorption. We plan to test two related hypotheses regarding the role of cytokines in the pathogenesis of osteoporosis. The first is that the variability in bone turnover and bone mass seen in older estrogen-deficient women is due to differences in local cytokine production. Although several cytokines have been implicated in postmenopausal osteoporosis, we will focus on the interleukin-1 system, including interleukin-1(, interleukin-1(, interleukin-1 receptor antagonist, interleukin-1 receptor 1, and interleukin-1 receptor 2. We hypothesize that high bone turnover and low bone mass will be positively correlated with IL-1 activity in older women. The second hypothesis is that estrogen modulates local cytokine production in bone and that differences in local cytokine production in bone explain the variability in response to estrogen. We hypothesize that IL-1 activity will increase when estrogen is withdrawn from older women who are current estrogen users at baseline and that IL-1 activity will decrease when estrogen is re-introduced and that the magnitude of the changes will be correlated with changes on bone turnover and bone mass.