BUILDING BONE IN OSTEOPOROSIS WITH PTH AND ESTROGEN

目前，没有药物被批准用于治疗 骨质疏松 虽然抗吸收剂似乎对 预防疾病，人们普遍认为他们的能力， 骨质增加充其量是适度的。 为了能在 治疗已确定的骨质疏松症，药物将需要有一个强大的 合成代谢作用 人体和动物体内研究表明，甲状旁腺激素（PTH） 以相对低的剂量间歇性地刺激骨 阵 这与其既定的能力形成鲜明对比， 当连续给予高剂量时刺激骨吸收。 PTH的这些矛盾作用的机制知之甚少， 但最近的体外研究结果表明， 这种作用可能与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 骨吸收，也可能对成骨细胞有影响 对正常的骨骼形成至关重要。 已充分证实 雌激素替代疗法（ERT）可防止加速的骨丢失 大多数女性在绝经后都会出现这种情况 此外，ERT通过 定义，只寻求恢复正常的雌激素功能，当 目前的艾滋病维持骨和矿物质的平衡。 拟议研究的目的是确定 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 脊椎骨矿物质，有利于增加强度超过治疗 单独的成分代理。 联合PTH 1-34 -雌激素治疗的骨效应将是 用常规的双能X射线吸收测定法监测 以及一种新的实验性方法 使用三维定量计算机断层扫描来评估 脊椎骨矿物质分布 其他成果措施将包括 包括血清碱性磷酸酶在内的骨标志物系列测量 骨钙素和尿吡啶啉交联。

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.