BUILDING BONE IN OSTEOPOROSIS WITH PTH AND ESTROGEN

用 PTH 和雌激素增强骨质疏松症的骨质

• 批准号: 2052145
• 负责人: CLAUDE D ARNAUD
• 金额: $ 31.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-06-11 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2052145
• 关键词: bone density; combination chemotherapy; computed axial tomography; estrogens; female; hormone therapy; human subject; human therapy evaluation; normal ossification; osteoporosis; parathyroid hormones; photon absorptiometry; postmenopause; skeletal disorder chemotherapy; tensile strength

At present, there are no drugs approved for the treatment of osteoporosis. While antiresorptive agents appear to be effective in preventing the disease, it is generally agreed that their ability to increase bone mass is modest at best. In order to be viable in the therapy of established osteoporosis, agents will need to have a strong anabolic effect. Studies in vivo in man and animals show that parathyroid hormone (PTH) administered in relatively low doses intermittently stimulates bone formation. This is in contrast to its well established ability to stimulate bone resorption when it is given in high doses continuously. The mechanisms of those paradoxical effects of PTH are poorly understood, but the results of recent studies in vitro suggest that the anabolic effects may be related to the ability of PTH to stimulate osteoblasts to produce insulin-like growth factor (IGF-I). Evidence has accumulated that estrogen acts directly to decrease osteoclastic bone resorption and may also have effects on the osteoblast that are essential to normal bone formation. It is well established that estrogen replacement therapy (ERT) prevents the accelerated bone loss that occurs in most women after the menopause. Furthermore, ERT, by definition, seeks only to restore normal estrogenic function, which when present aids in maintaining both bone and mineral balance. The purpose of the proposed investigation is to determine the efficacy of the combined administration of synthetic human parathyroid hormone fragment, 1-34, (HPTH 1-34) and estrogen- progesterone replacement in the treatment of postmenopausal women with osteoporosis. We hypothesize that such treatment will increase bone mass and effect a distribution of vertebral bone mineral that favors increased strength more than treatment with individual constituent agents alone. The osseous effects of combined PTH 1-34 - estrogen therapy will be monitored with conventional dual energy x-ray absorptiometry measurements of the spine, hip and forearm, as well as a new, experimental approach using three-dimensional quantitative computed tomography to assess vertebral bone mineral distribution. Other outcome measures will include serial measurement of bone markers including serum alkaline phosphatase and osteocalcin, and urine pyridinoline crosslinks.

目前，尚未批准用于治疗的药物 骨质疏松症。 尽管抗吸收剂似乎有效 防止疾病，人们普遍认为他们的能力 增加骨骼质量充其量是适中的。 为了在 既定的骨质疏松症的治疗，代理将需要具有强大的疗法 合成代谢效应。 人类和动物的体内研究表明甲状旁腺激素（PTH） 以相对较低的剂量间歇性刺激骨骼 形成。 这与其确定的能力相反 当骨吸收连续给予高剂量时。 PTH的矛盾作用的机制知之甚少， 但是最近在体外研究的结果表明合成代谢 效果可能与PTH刺激成骨细胞的能力有关 产生胰岛素样生长因子（IGF-I）。 有证据表明雌激素直接起作用以减少 整骨骨吸收，也可能对成骨细胞产生影响 对于正常的骨形成至关重要。 已经确定了 雌激素替代疗法（ERT）阻止了加速的骨质流失 这是在更年期之后的大多数女性中发生的。 此外，Ert，by 定义，只是旨在恢复正常的雌激素功能，当 现在有助于维持骨骼和矿物质平衡。 拟议调查的目的是确定 合成人甲状旁腺激素的组合给药 片段，1-34，（HPTH 1-34）和雌激素 - 孕酮的替代 骨质疏松症的绝经后妇女的治疗。 我们假设这一点 这种治疗将增加骨骼质量并影响 椎骨矿物质比治疗更大的强度增加了强度 独自与单个组成代理人。 PTH 1-34-雌激素治疗的骨作用将是 用常规双能X射线吸收法测量测量 脊柱，臀部和前臂以及一种新的实验方法 使用三维定量计算机断层扫描来评估 椎骨矿物质分布。 其他结果措施将包括 包括血清碱性磷酸酶在内的骨标记的连续测量 和骨钙素，以及尿吡啶胺交联。