BISPHOSPHONATE BONE QUALITY IN WOMEN WITH BREAST CANCER

乳腺癌女性双磷酸盐骨质量

• 批准号: 7285270
• 负责人: SUSAN M OTT
• 金额: --
• 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 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7285270
• 关键词: Alkaline Phosphatase; Animals; Biochemical Markers; Biochemistry; Biomechanics; Biopsy; Biopsy Specimen; Bone Density; Bone Resorption; Bone Surface; Cancer Patient; Clinical Protocols; DEXA; Data; Deposition; Diagnosis; Dichloromethylene Diphosphonate; Disease; Dose; Electrons; End Point; Enrollment; Failure; Fluorides; Fracture; Frequencies; Funding; Hip region structure; Human; Ibandronate; Image; Incidence; Intravenous; Invasive; Kinetics; Label; Measurement; Measures; Mental Depression; Metastatic Neoplasm to the Bone; N-telopeptide; Neoplasm Metastasis; Oral; Osteogenesis; Osteoid; Osteoporosis; Pharmaceutical Preparations; Physiology; Positron-Emission Tomography; Postmenopause; Premenopause; Property; Protocols documentation; Randomized; Rate; Research; Research Personnel; Roentgen Rays; Serum; Skeletal system; Skeleton; Southwest Oncology Group; Staging; Stress; Structure; Surface; Techniques; Testing; Tetracycline; Tetracyclines; Thick; Time; Tissues; Vertebral column; Width; Woman; Work; X-Ray Computed Tomography; Zoledronate; bisphosphonate; bone; bone health; bone imaging; bone loss; bone quality; bone strength; bone toughness; bone turnover; day; density; improved; malignant breast neoplasm; mineralization; prevent; time use; uptake

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）：双膦酸盐可以降低乳腺癌女性骨转移的发生率，但生存数据不一致。因此，西南肿瘤学小组正在进行一项为期 3 年的临床方案，招募 6,000 名女性，随机接受氯膦酸盐、伊班膦酸盐或唑来膦酸盐治疗，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的生存率。这些剂量比用于治疗骨质疏松症的剂量大两到十倍，并且高剂量双磷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微损伤累积和材料特性异常。乳腺癌研究提供了一个难得的机会来评估双磷酸盐引起的人类骨质量和骨生理学的变化。假设高剂量双膦酸盐治疗将导致骨吸收和形成的严重抑制、矿化密度增加和骨内在韧性降低。对于该提案，90 名绝经前妇女将在双膦酸盐治疗前后接受四环素标记的髂嵴骨活检、双 X 射线吸收法骨密度测量以及骨转换的血清生化标记物。将通过微型计算机断层扫描测量骨骼的结构参数，包括连接性、骨体积和皮质厚度。压缩生物力学测试将确定刚度（杨氏模量）、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速率和激活频率。矿化密度将使用背散射电子成像来测量。其中 27 名女性将通过 18 氟化物 PET 扫描对骨骼中氟化物沉积进行动力学分析。该研究结果将提供有关高剂量双磷酸盐对人类骨骼影响的有价值的信息。