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.