BUILDING BONE IN OSTEOPOROSIS WITH PTH AND ESTROGEN

目前，还没有被批准用于治疗糖尿病的药物。 骨质疏松。而抗吸收药物似乎在 预防疾病，人们普遍认为他们有能力 增加骨量充其量是适度的。为了能够在世界上生存 治疗已确立的骨质疏松症，药剂需要有较强的 合成代谢作用。 在人和动物体内的研究表明，甲状旁腺激素(PTH) 以相对较低的剂量间歇地刺激骨骼 队形。这与其成熟的能力形成了鲜明对比 持续高剂量服用可刺激骨吸收。 甲状旁腺素的这些矛盾效应的机制还知之甚少， 但最近的体外研究结果表明，合成代谢 其作用机制可能与甲状旁腺素刺激成骨细胞 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 破骨细胞性骨吸收，也可能对成骨细胞产生影响 对正常的骨骼形成是必不可少的。众所周知， 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发生这种情况。此外，ERT，由 定义，只寻求恢复正常的雌激素功能，当 本产品有助于维持骨骼和矿物质的平衡。 拟议的调查的目的是确定 人工合成人甲状旁腺激素的联合应用 片段1-34，(HPTH 1-34)和雌孕激素替代 绝经后妇女骨质疏松的治疗。我们假设 这种治疗将增加骨量，并影响分布 比起治疗更有利于增加强度的椎骨矿物质 单独与单独的组成人员合作。 甲状旁腺素1-34-雌激素联合治疗的骨质效应将是 用常规的双能x射线吸收测量法监测 脊椎、臀部和前臂，以及一种新的实验方法 应用三维定量计算机体层摄影术评估 椎骨矿物质分布。其他成果衡量标准将包括 血清碱性磷酸酶等骨标志物的系列检测 骨钙素和尿吡啶酚的交联物。

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.