Management of Cancer-Treatment-Induced Bone Loss

简介(申请人提供)：癌症流行病学家Luke Peppone博士，M.P.H.正在申请职业发展导师奖，以扩大他的研究技能，成为癌症控制领域的独立临床调查员，专注于开发和测试治疗癌症治疗引起的骨丢失(CTIBL)的干预措施。这项提案将评估旨在预防由芳香酶抑制剂(AI)治疗导致的绝经后乳腺癌患者CTIBL的干预措施，该治疗导致该人群的骨丢失增加2-4倍，并显著增加骨折风险。该研究项目将测试大剂量维生素D补充剂和个性化负重锻炼计划预防CTIBL的有效性。职业发展计划：Peppone博士以前作为癌症流行病学家的经验，再加上他作为临床癌症控制研究员正在接受的培训，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员。他的培训目标将扩展他的知识，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)在第二/III期随机对照临床试验的设计、实施和分析方面获得PI的经验，以及3)在CTIBL的营养补充干预(维生素D)和行为干预(运动)的测试和实施方面获得经验。加里·莫罗博士是过去30年来领先的癌症控制研究人员，他将担任佩彭博士的主要高级导师，并提供 指导临床试验领域的工作。共同导师Randy Rosier博士和顾问Alissa Huston博士将提供CTIBL的生物学、生理学和促成因素方面的专业知识。共同导师Mary Reid博士和Donald Trump顾问将为CTIBL的管理提供维生素D功效和药理学方面的经验，而共同导师Karen Mustian博士将培训Peppone博士开发和实施CTIBL的运动干预措施。Godfrey博士顾问将提供基因分析方面的培训，Heckler顾问博士将提供统计培训。研究计划：拟议的试验性随机对照试验，基于生物学上的合理性和可行性数据，是一项三臂研究，旨在测试两种预防癌症治疗引起的骨丢失的干预措施，这些患者中有105名接受辅助人工智能治疗的中度维生素D缺乏(11-32 ng/ml)的绝经后乳腺癌患者。这项拟议的临床试验旨在评估：1)高剂量维生素D补充剂，2)高剂量维生素D补充剂加上单独定制的居家负重有氧(步行)和渐进性阻力运动计划，与3)低剂量维生素D补充剂对骨代谢和骨密度的影响进行比较。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参考。Peppone博士将利用该奖项获得的培训和数据，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.