HORMONE REPLACEMENT THERAPY ON BONE TURNOVER AND DENSITY IN OLDER WOMEN

骨质疏松性骨折是#年发病率和死亡率的主要来源 年长的女人。女性髋部骨折的发病率每五年增加一倍。 40岁后的性行为；25%-30%的髋部骨折女性失去了 由于骨折而独立。脊椎粉碎性骨折 随着年龄的增长而增加，可能会导致严重的疼痛和功能性 拒绝。尽管70岁以上的女性患糖尿病的风险最高 骨质疏松性髋部和脊柱骨折，大多数研究都集中在 预防新近更年期妇女的骨折。我们建议 一项由三部分组成的干预发展研究(IDS)需要仔细检查 雌激素对骨局部因子、骨转换和骨的影响 失落在臀部。 入侵检测系统1的A部分将检查骨骼剂量响应，其测量方法为 骨转换的生化标记物，随机、连续6周 微粉化17β-雌二醇(0.25 mg、0.5 mg、1.0 mg)疗程。六十 按年龄(55-69岁或70-85岁)分层的妇女将被 随机接受一种治疗方案(按雌激素的顺序排列)。血清和 将收集尿液以进行生化标记物的测定 基线，每次治疗6周，治疗后6周 雌激素。每次注射之间将有6周的洗脱期； 所有女性都将接受每一剂量的雌激素。我们还将确定 降低老年人骨转换的最低雌激素剂量 组；此剂量将在入侵检测系统1的b部分使用。B部分为期2年 比较雌激素、钙、三者联合作用的研究 雌激素钙与对照组髋部骨密度的关系 70-85岁以上的女性。160名妇女将被随机抽查 以上治疗组治疗2年。入侵检测系统#1的C部分是试验性的 局部调控因子基因表达的定量化研究 接受雌激素停用或停用的女性体内的构成蛋白 雌激素替代疗法。我们将招募12名70岁以上的女性-6名 在过去10年中没有接受雌激素治疗的患者(第1组)和接受过雌激素治疗的患者6例 服用雌激素至少2年(第2组)。组1将被放置 每天1.0毫克的17β-雌二醇和第2组将从 雌激素。通过逆转录从小鼠的小分子中提取基因 基线和3个月后取髂骨穿刺骨活检 雌激素撤除或替代。 如果老年女性的骨骼比年轻女性对ERT更敏感，那么 较低的剂量可能会减少骨转换，防止髋部的骨丢失。 不会产生不良反应，如乳房压痛和积液 保留，这是女性接受ERT的两个非常常见的抱怨。因此，更老的 女性可能更愿意接受ERT。此外，如果这些研究 表现出与以下方面相关的地方监管机构的显著差异 雌激素缺乏和替代，结果可能导致新的 预防和治疗老年人骨丢失的方法。

Osteoporotic fractures are a major source of morbidity and mortality in older women. The incidence of hip fractures in women doubles every five to sex years after age 40; 25-30% of women with hip fracture lose their independence as a result of fracture. Vertebral crush fractures also increase with age and may result in substantial pain and functional decline. Although women over 70 years are at the highest risk for osteoporotic hip and spine fractures, most research has focused on prevention of fractures in more recently menopausal women. We propose a three- part intervention development study (IDS) to closely examine the effect of estrogen on local factors in bone, bone turnover, and bone loss at the hip. Part A of IDS#1 will examine skeletal dose response, as measured by biochemical markers of bone turnover, to randomized, sequential 6-week courses of micronized 17beta-estradiol (0.25mg, 0.5 mg, 1.0 mg.). Sixty women, stratified by age (55-69 years or 70-85 years), will then be randomized to a treatment regimen (order of estrogen does). Serum and urine will be collected for measurement of biochemical markers at baseline, 6 weeks on treatment and 6 weeks post-treatment for each dose of estrogen. There will be a 6-week wash-out period between each dose; all woman will receive each dose of estrogen. We will also determine the lowest dose of estrogen to decrease bone turnover in the older age group; this dose will be used in Part b of IDS#1. Part B is a 2-year study to compare the effect of estrogen, calcium, the combination of estrogen and calcium and a control group on bone density at the hip in women over 70-85 years. One-hundred and sixty women will be randomized to the above treatment groups for 2 years. Part C of IDS#1 is a pilot study to quantitate gene expression of local regulatory factors and constitutive proteins in of women who undergo estrogen withdrawal or estrogen replacement. We will recruit 12 women over 70 years -6 who have not received estrogen in the past 10 years (group 1) and 6 who have been on estrogen for at least 2 years (group 2). Group 1 will be placed on 1.0 mg/d 17beta-estradiol and Group 2 will be withdrawn from estrogen. cDNA will be prepared by reverse transcribing mRNA from small needle iliac crest biopsy obtained at baseline and 3 months after estrogen withdrawal or replacement. If bone in older women is more sensitive to ERT than younger women, then a lower dose might reduce bone turnover and prevent bone loss at the hip without producing adverse effects, such as breast tenderness and fluid retention, two very common complaints of women taking ERT. Thus, older women may be more willing to accept ERT. Further, if these studies demonstrate substantial differences in local regulators associated with estrogen deficiency and replacement, the results could lead to new approaches to the prevention and therapy of bone loss in older adults.