BISPHOSPHONATE BONE QUALITY IN WOMEN WITH BREAST CANCER

乳腺癌女性双磷酸盐骨质量

• 批准号: 6967087
• 负责人: SUSAN M OTT
• 金额: $ 49.62万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-25 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6967087
• 关键词: biopsy; blood chemistry; bone density; bone metabolism; bone neoplasms; breast neoplasms; cancer complication; cancer prevention; chemoprevention; clinical research; computed axial tomography; diphosphonate; dosage; drug adverse effect; female; human subject; human therapy evaluation; metastasis; neoplasm /cancer invasiveness; neoplasm /cancer relapse /recurrence; outcomes research; pathologic bone resorption; photon absorptiometry; positron emission tomography; women' s health

DESCRIPTION (provided by applicant): Bisphosphonates may reduce the incidence of bone metastases in women with breast cancer, but survival data are inconsistent. The Southwest Oncology Group is therefore conducting a 3 year clinical protocol enrolling 6,000 women with randomization to clodronate, ibandronate or zoledronate to determine whether high doses of these bisphosphonates can prevent bone metastases and improve survival in women with breast cancer. The doses are two to ten times greater than those used to treat osteoporosis, and the effects of high-dose bisphosphonates on the bone health in these women are uncertain. Animal studies have shown that high-dose bisphosphonates caused microdamage accumulation and abnormal material properties of the bone. The breast cancer study provides an exceptional opportunity to evaluate bisphosphonate-induced changes in bone quality and bone physiology in humans. The hypothesis is that high-dose bisphosphonate therapy will result in profound depression of bone resorption and formation, increased mineralization density and decreased intrinsic toughness of the bone. For this proposal, a subset of 90 premenopausal women will undergo tetracycline-labeled iliac crest bone biopsies, bone density measurements by dual x ray absorptimetry and serum biochemical markers of bone turnover before and after bisphosphonate treatment. The bone will be measured with micro-computed tomography for structural parameters including connectivity, bone volume, and cortical thickness. Biomechanical testing in compression will determine the stiffness (Young's modulus), yield point, toughness and strength. Histomorphometric measurements of bone surfaces will allow calculations of bone formation rates and activation frequency. Mineralization density will be measured using backscattered electron imaging. A subset of 27 women will undergo kinetic analysis of fluoride deposition in bone by 18-Fluoride PET scans. Results of the study will provide valuable information about skeletal effects of high-dose bisphosphonates in humans.

描述（由申请人提供）：双膦酸盐可能会降低乳腺癌女性骨转移的发生率，但生存数据不一致。因此，西南肿瘤学组正在进行3年的临床方案，该方案招募了6,000名具有随机分配给氯膦酸盐，i灯膦酸盐或唑来膦酸盐的女性，以确定高剂量的这些双膦酸盐是否可以防止骨转移酶并改善乳腺癌女性的生存率。剂量比治疗骨质疏松症的剂量大2到十倍，而高剂量双膦酸盐对这些女性骨骼健康的影响尚不确定。动物研究表明，高剂量的双膦酸盐会导致骨骼的微塑料积累和异常的材料特性。乳腺癌研究为评估双膦酸盐诱导的人类骨质和骨生理变化提供了极大的机会。假设是，高剂量的双膦酸盐治疗将导致骨吸收和形成，矿化密度增加和骨骼内在韧性降低。对于这一提议，一部分90个绝经前女性将接受四环素标记的iLiac Crest骨活检，双X射线吸收率和血清生化标记在双膦酸盐治疗前后，骨密度测量以及血清生化标志物。骨头将用微型层析成像测量，用于结构参数，包括连通性，骨骼体积和皮质厚度。压缩中的生物力学测试将决定刚度（Young的模量），产量点，韧性和强度。骨表面的组织形态测量结果将允许计算骨形成速率和激活频率。矿化密度将使用反向散射的电子成像测量。 27名妇女的子集将通过18-氟化物PET扫描对骨中的氟化物沉积进行动力学分析。该研究的结果将提供有关大剂量双膦酸盐在人类中的骨骼影响的有价值信息。