Management of Cancer-Treatment-Induced Bone Loss

描述（由申请人提供）：Luke Pepperly，Ph.D.，M.P.H.癌症流行病学家，正在申请一个指导职业发展奖，以扩大他的研究技能，并成为一个独立的临床研究人员在癌症控制，重点是开发和测试干预措施，以治疗癌症治疗引起的骨质流失（CTIBL）。该提案将评估旨在预防芳香化酶抑制剂（AI）治疗引起的绝经后乳腺癌患者CTIBL的干预措施，该治疗导致骨丢失增加2至4倍，并显着增加该人群的骨折风险。该研究项目将泰特高剂量维生素D补充剂加上个性化的负重锻炼计划预防CTIBL的功效。职业发展计划：Pepperly博士以前作为一名专门从事癌症研究的流行病学家的经验，加上他作为临床癌症控制研究人员的持续培训，使他非常适合成为一名专注于CTIBL发病机制和治疗的独立研究人员。他的培训目标将扩展他的知识，并分为三个培训目标：1）发展CTIBL的生物学、生理学、遗传学和测量方面的专业知识，2）作为PI在II/III期随机对照临床试验的设计、实施和分析方面积累经验，以及3）在CTIBL的营养补充干预（维生素D）和行为干预（运动）的测试和实施中获得经验。加里莫罗，一个领先的癌症控制研究人员在过去的三十年，将担任博士的主要高级导师，并提供 临床试验实施领域的指导。共同导师兰迪·罗西尔博士和顾问艾丽莎·休士顿博士将提供CTIBL生物学、生理学和促成因素方面的专业知识。共同导师玛丽里德博士和顾问唐纳德特朗普提供的经验，在疗效和药理学的维生素D的管理CTIBL，而共同导师博士卡伦Mustian将培训博士Pepperly在开发和实施运动干预CTIBL。顾问戈弗雷博士将提供遗传分析培训，顾问赫克勒博士将提供统计培训。研究计划：基于生物相容性和可行性数据，拟议的试点RCT是一项三臂研究，在105名接受辅助AI治疗的中度维生素D缺乏（11-32 ng/ml）绝经后乳腺癌患者中测试两种干预措施预防癌症治疗诱导的骨丢失。拟议的临床试验旨在评估以下方面的疗效：1）高剂量维生素D补充剂，2）高剂量维生素D补充剂加上个性化定制的家庭负重有氧（步行）和渐进式阻力运动计划，与3）低剂量维生素D补充剂相比，对骨代谢和骨矿物质密度的影响。所提供的数据将支持更明确的III期临床试验，并可能为CTIBL治疗的循证医学实践提供信息。Pepperly博士将利用此次获奖获得的培训和数据，发展成为癌症控制领域的独立临床研究人员。

DESCRIPTION (provided by applicant): Luke Peppone, Ph.D., M.P.H., a cancer epidemiologist, is applying for a mentored career development award to expand his research skills and become an independent clinical investigator in cancer control with a focus on developing and testing interventions to treat cancer-treatment-induced bone loss (CTIBL). This proposal will assess interventions aimed at preventing CTIBL in postmenopausal breast cancer patients caused by aromatase inhibitor (AI) therapy, which results in a 2- to 4-fold increase in bone loss and significantly increase fracture risk in this population. The research project will tet the efficacy of high-dose vitamin D supplementation plus a personalized weight-bearing exercise program to prevent CTIBL. Career Development Plan: Dr. Peppone's previous experience as an epidemiologist specializing in cancer, combined with his ongoing training as a clinical cancer control researcher, makes him well-suited to become a independent researcher with a focus on the pathogenesis and treatment of CTIBL. His training goals will expand upon his knowledge and are divided into three training aims: 1) to develop expertise in the biology, physiology, genetics, and measurement of CTIBL, 2) to gain experience as a PI in the design, conduct, and analysis of Phase II/III randomized controlled clinical trials, and 3) to gain experience in the testing and implementation of a nutritional supplement intervention (vitamin D) and behavioral interventions (exercise) for CTIBL. Dr. Gary Morrow, a leading cancer control researcher for the past thirty years, will serve as Dr. Peppone's principal senior mentor and offer guidance in the area of clinical trial conduct. Co-mentor Dr. Randy Rosier and Advisor Dr. Alissa Huston will provide expertise in the biology, physiology, and contributing factors of CTIBL. Co-mentor Dr. Mary Reid and Advisor Donald Trump offer experience in the efficacy and pharmacology of vitamin D for the management of CTIBL, while co-mentor Dr. Karen Mustian will train Dr. Peppone in the development and implementation of exercise interventions for CTIBL. Advisor Dr. Godfrey will provide training in genetic analysis and Advisor Dr. Heckler will offer statistical training. Research Plan: The proposed pilot RCT, based upon both biological plausibility and feasibility data, is a three-arm study that tests two interventions for the prevention of cancer-treatment-induced bone loss in 105 moderately vitamin D deficient (11-32 ng/ml) postmenopausal breast cancer patients undergoing adjuvant AI therapy. The proposed clinical trial aims to evaluate the efficacy of: 1) high-dose vitamin D supplementation, 2) high-dose vitamin D supplementation plus an individually tailored home-based weight-bearing aerobic (walking) and progressive resistance exercise program, compared to 3) low-dose vitamin D supplementation on bone metabolism and bone mineral density. Data provided will support a more definitive phase III clinical trial and potentially inform the practice of evidence-based medicine for the treatment of CTIBL. Dr. Peppone will use the training and data obtained by this award to develop into an independent clinical researcher in the cancer control field.