RESTORING BONE IN OSTEOPENIC FEMALE SKELETON

恢复骨质疏松女性骨骼的骨骼

• 批准号: 3158497
• 负责人: WEBSTER S JEE
• 金额: $ 22.13万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3158497
• 关键词: aging; bone density; bone metabolism; diphosphonate; disease /disorder model; disease /disorder prevention /control; estrogens; female; histology; laboratory rat; osteoporosis; parathyroid hormones; physiologic bone resorption; prostaglandin E

Osteoporosis is mainly a disease of elderly women, who have low cancellous and cortical bone mass, poor bone structure, and fragility fractures. Though osteoporosis can be prevented by maintaining "peak" bone mass, treating it by substantially increasing bone strength is difficult. We propose using osteopenic, aged female rats to test a two-phase concept to treat established osteopenia. Since it has an anabolic phase to restore lost bone and a maintenance phase to preserve the new bone, it is named Activate->Restore->Maintain (A->R->M). We propose two experiments using aged female rats with established osteopenia originating from estrogen-depletion or chronic disuse, or a combination of the two. We will use either prostaglandin E2 (PGE2) or parathyroid hormone (hPTH) as anabolic agents to restore lost bone (+Phase). Past experience with both shows that their discontinuation is associated with rapid disappearance of the new bone they induce. When we stop +Phase, we will switch to an agent known chiefly for its ability to block bone loss (+Phase). We will use either 17-beta-estradiol (E2) or risedronate, a bisphosphonate. We will study animals at the beginning of +Phase, at the close of +Phase, and twice during +Phase, to establish both the permanence of the new bone and its incorporation into the adult skeleton by modeling and remodeling processes. A third experiment examines the ability of co-treatment with a resorption inhibitor and an anabolic agent, to add new bone, yet avoid an early transient phase of bone loss. For endpoints, we plan quantitative histologic studies of bone mass, structure, and turnover in the cancellous bone of the proximal and distal tibial metaphyses, and cortical bone of the tibio-fibular junction. We hypothesize that bone mass of the osteopenic skeleton improves during treatment with an anabolic agent, and then is permanently maintained by other routinely available agents. We hypothesize that differences in estrogen-depletion and disuse-related osteopenia exist, such that risedronate can, but E2 cannot, maintain new bone in the skeleton of an animal suffering chronic disuse osteopenia. We hypothesize that co- treating with a resorption inhibitor allows anabolic agents to work normally, while blocking the consequences of any early resorption phase. A->R->M, that limits the use of skeletal anabolic agents to the time when they are most effective, could hasten the application of such agents for treating osteoporosis.

骨质疏松症主要是老年妇女的疾病 以及皮质骨骼，骨骼结构不良和脆弱性骨折。 尽管可以通过保持“峰”骨骼来预防骨质疏松症，但 通过大幅提高骨强度来治疗它是困难的。 我们 建议使用骨质减少型，老年雌性大鼠测试两相概念 治疗已建立的骨质减少症。 由于它具有恢复代谢阶段 失去的骨头和维护新骨头的维护阶段，命名为 激活 - >恢复 - >维护（A-> R-> m）。 我们提出了两个实验，使用老年雌性大鼠已建立 骨质减少症起源于雌激素止血或慢性废弃，或 两者的组合。 我们将使用前列腺素E2（PGE2）或 甲状旁腺激素（HPTH）作为合成代谢剂，以恢复损失的骨骼 （+阶段）。 两者的过去经验表明，他们的停产是 与它们诱导的新骨头快速消失有关。 当我们 停止 +阶段，我们将主要因其能力而主要闻名的代理商 阻塞骨丢失（+相）。 我们将使用17-β-雌二醇（E2）或 risdronate，双膦酸盐。 我们将在开始时研究动物 +相位，在 +相结束时，在 +阶段两次，以建立同时建立 新骨的永久性及其成人的掺入 通过建模和重塑过程进行骨骼。 第三个实验检查 与吸收抑制剂和合成代谢的共同治疗的能力 代理，增加骨头，但避免了早期的骨质流失阶段。 对于终点，我们计划骨骼质量的定量组织学研究 结构和近端和远端的取消骨的离职 胫骨形而上学和胫骨连接的皮质骨。 我们假设骨质减少骨骼的骨质量在 用合成代谢剂处理，然后由 其他常规代理。 我们假设在 存在雌激素止血和与废药相关的骨质减少症，以至于 risdronate可以，但是E2不能在一个骨骼中保持新骨头 患有慢性废除骨质减少的动物。 我们假设该共同 用吸收抑制剂治疗允许合成代谢剂工作 通常，同时阻止任何早期吸收阶段的后果。 a-> r-> m，将骨骼合成代谢剂的使用限制为 它们最有效，可以加速此类代理商的应用 治疗骨质疏松症。