Project Summary This K23 proposal will provide Calyani Ganesan, MD, MS with dedicated time, mentorship, training, and research experience to become an independent clinical investigator. Dr. Ganesan is a clinician-scientist with a long-term vision of improving the quality of care for patients with urinary stones. Under the guidance of a strong mentorship team, she will acquire skills in: 1) advanced statistical methods used in pharmacoepidemiology studies; 2) the collection and analysis of prospective patient data; and 3) a novel bone imaging technique, high-resolution peripheral quantitative computed tomography (HR-pQCT), to assess skeletal status. This grant proposes to improve the screening and management of patients with urinary stone disease and diminished bone strength. Despite an increased risk of fracture in patients with urinary stone disease, there are currently no guidelines regarding the screening and treatment of osteoporosis in these patients. It is also unclear which medications might provide dual benefit in decreasing skeletal fragility and reducing stone recurrence in these patients. This project aims to: 1) identify patients with urinary stone disease who are at high risk for osteoporosis or fracture; 2) determine the effects of medications used to treat osteoporosis on urinary stone disease; and 3) identify the underlying bone deficits in patients with urinary stone disease using HR-pQCT and bone biomarkers reflecting bone formation and resorption. The first two aims will be answered by analyzing national data from the Veterans Health Administration (VHA) and Optum datasets. For the third aim, Dr. Ganesan will recruit patients with urinary stone disease from the Stanford University and Veterans Affairs Palo Alto Health Care System Kidney Stone clinics. She will use HR-pQCT and serum biomarkers to measure and monitor bone parameters over time in these patients. The proposed work has potential to make a significant clinical impact. Successful completion will enable clinicians to identify which patients with urinary stone disease should be screened osteoporosis and inform clinicians how best to treat these patients so that fracture associated comorbidity and recurrent stones can be reduced. The proposed work is realistic and feasible within the award period, and the research infrastructure at Stanford is already in place. Dr. Ganesan is poised to build on her research skills, advance and disseminate scientific knowledge, create additional collaborative networks, and eventually compete for R01 or equivalent funding. In summary, the K23 award will provide the support to enable Dr. Ganesan to become a successful independent clinical investigator.