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.

目前尚无批准用于治疗该病的药物 骨质疏松症。 虽然抗再吸收药物似乎有效 预防这种疾病，人们普遍认为他们有能力 骨量的增加充其量是适度的。 为了能够在 治疗已确定的骨质疏松症，药物需要具有很强的 合成代谢作用。 人和动物体内研究表明，甲状旁腺激素 (PTH) 以相对较低的剂量间歇性地刺激骨骼 形成。 这与其公认的能力形成鲜明对比 连续给予高剂量时会刺激骨吸收。 PTH 这些矛盾效应的机制人们知之甚少， 但最近的体外研究结果表明，合成代谢 其作用可能与 PTH 刺激成骨细胞的能力有关 产生胰岛素样生长因子（IGF-I）。 越来越多的证据表明雌激素直接作用于减少 破骨细胞骨吸收，也可能对成骨细胞有影响 这对于正常的骨形成至关重要。 众所周知 雌激素替代疗法（ERT）可防止加速骨质流失 大多数女性在绝经后都会出现这种情况。 此外，ERT，通过 定义，仅寻求恢复正常的雌激素功能，当 有助于维持骨骼和矿物质平衡。 拟议调查的目的是确定以下措施的有效性： 合成人甲状旁腺激素的联合给药 片段 1-34（HPTH 1-34）和雌激素-孕激素替代 治疗绝经后妇女骨质疏松症。 我们假设 这种治疗将增加骨量并影响骨量的分布 比治疗更有利于增加强度的椎骨矿物质 单独与单独的组成主体。 PTH 1-34 - 雌激素联合治疗的骨质效应将是 通过传统双能 X 射线吸收测定法测量进行监测 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 椎骨骨矿物质分布。 其他成果衡量标准将包括 骨标志物的连续测量，包括血清碱性磷酸酶 和骨钙素，以及尿吡啶啉交联。