Management of Cancer-Treatment-Induced Bone Loss

描述（由申请人提供）：Luke Peppone博士，M.P.H，癌症流行病学家，正在申请指导职业发展奖，以扩大他的研究技能，并成为癌症控制方面的独立临床研究者，专注于开发和测试治疗癌症治疗引起的骨质流失（CTIBL）的干预措施。该提案将评估旨在预防芳香酶抑制剂（AI）治疗引起的绝经后乳腺癌患者CTIBL的干预措施，该干预措施导致该人群骨质流失增加2至4倍，并显著增加骨折风险。该研究项目将测试高剂量维生素D补充剂加上个性化负重锻炼计划预防CTIBL的效果。职业发展规划：Peppone博士之前作为癌症流行病学家的经验，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，实施和分析方面获得经验；3)获得CTIBL的营养补充剂干预（维生素D）和行为干预（运动）的测试和实施方面的经验。Gary Morrow博士是过去三十年来癌症控制研究的领军人物，他将担任Peppone博士的主要高级导师和顾问

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.