EFFECT OF MINOCYCLINE IN POSTMENOPAUSAL OSTEOPOROSIS

米诺环素对绝经后骨质疏松症的作用

• 批准号: 6281961
• 负责人: JAY Robert SHAPIRO
• 金额: $ 5.69万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281961
• 关键词: bone density; clinical research; human subject; human therapy evaluation; longitudinal human study; osteoblasts; osteoporosis; postmenopause; skeletal disorder chemotherapy; tetracyclines

Osteoporosis is a major public health problem for women and men in the United States. The problem of osteoporosis increases as the population ages. Current treatments for osteoporosis, such as dietary calcium supplements, estrogen replacement therapy, bisphosphonates and calcitonin, are largely aimed at decreasing the rate of bone resorption. Bone formation is eventually limited during the use of antiresorptive therapies due to osteoblast/osteoclast coupling. No agent with a primary effect of increasing bone formation, such as fluoride or human parathyroid hormone, is available for therapy. Tetracycline and tetracycline derivatives are known to bind to the mineralization front in bone and are recognized to inhibit osteoclast activity. Tetracyclines, including minocycline, also inhibit the activity of mammalian collagenase and inhibit parathyroid hormone-induced bone resorption in tissue culture. In vivo histomorphometric studies in rodents indicate that minocycline may also increase the rate of bone formation, as well as decrease the rate of bone resorption leading to a net increase in bone mass. To determine if minocycline has direct effects on osteoblast function, we will assess the minocycline effect on the synthesis of skeletal matrix proteins by human osteoblastic cells in vitro. We hypothesize that the administration of minocycline for one year to osteoporotic postmenopausal women at a dose of 200 mg/day with a minimum calcium intake of 800 mg/day and 400 U vitamin D, will induce an increase in bone mineral density with minimal toxicity. This is a placebo-controlled, masked Phase II study that will be expanded if a positive effect on bone density is observed after one year of treatment.

骨质疏松症是一个主要的公共卫生问题的妇女和男子， 美国的骨质疏松症的问题随着人口的增加而增加 年龄目前治疗骨质疏松症，如膳食钙 补充剂，雌激素替代疗法，双膦酸盐和降钙素， 主要是为了降低骨吸收率。骨 在使用抗吸收疗法期间， 由于成骨细胞/破骨细胞偶联。无主要作用为 增加骨形成，如氟化物或人甲状旁腺激素， 可用于治疗。四环素和四环素衍生物是 已知与骨中的矿化前沿结合， 抑制破骨细胞活性。四环素类，包括米诺环素，也 抑制哺乳动物胶原酶活性，抑制甲状旁腺 组织培养中的骨诱导骨吸收。体内 啮齿类动物的组织形态计量学研究表明，米诺环素也可能 增加骨形成的速率，以及降低骨形成的速率。 吸收导致骨量净增加。以确定是否 米诺环素对成骨细胞功能有直接影响，我们将评估 米诺环素对人骨基质蛋白合成的影响 体外培养成骨细胞。我们假设， 米诺环素一年的剂量为 200毫克/天，最低钙摄入量为800毫克/天和400 U维生素 D，将以最小的毒性诱导骨矿物质密度增加。 这是一项安慰剂对照、设盲的II期研究， 如果在一年后观察到对骨密度的积极影响， 治疗