BISPHOSPHONATE BONE QUALITY IN WOMEN WITH BREAST CANCER

乳腺癌女性双磷酸盐骨质量

• 批准号: 7124686
• 负责人: SUSAN M OTT
• 金额: $ 46.54万
• 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/7124686
• 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(申请人提供)：双膦酸盐可以降低乳腺癌女性患者的骨转移发生率，但存活率数据并不一致。因此，西南肿瘤学小组正在进行一项为期3年的临床方案，招募6000名妇女随机服用氯屈膦、伊班磷酸钠或唑来膦酸盐，以确定高剂量的这些双磷酸盐是否可以预防骨转移并提高乳腺癌女性患者的存活率。这种剂量是用于治疗骨质疏松症的剂量的两到十倍，而大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，大剂量的双膦酸盐会导致骨骼的微损伤堆积和材料特性异常。乳腺癌研究提供了一个难得的机会来评估双膦酸盐引起的人类骨骼质量和骨生理的变化。假设大剂量双磷酸盐治疗会导致骨吸收和骨形成的严重抑制，增加矿化密度和降低骨的固有韧性。根据这项建议，90名绝经前妇女的子组将在双磷酸盐治疗前后接受四环素标记的髂骨活组织检查、双X射线吸收仪骨密度测量和血清骨转换生化标记物。将用微型计算机断层扫描测量骨骼的结构参数，包括连通性、骨体积和皮质厚度。压缩下的生物力学测试将确定刚度(杨氏模数)、屈服点、韧性和强度。骨表面的组织形态测量将允许计算骨形成率和激活频率。矿化密度将使用背散射电子成像进行测量。27名女性的子组将通过18-氟化物PET扫描进行氟化物在骨骼中沉积的动力学分析。这项研究的结果将提供关于高剂量双膦酸盐对人体骨骼影响的有价值的信息。