Integrated genomic profiling and Imaging clustering of patients (clinical setting): The objective of this work package is to translate genomic discoveries and imaging insights on skeletal fragility into clinical practice, with the aim of improving patient care. Genomic studies provide a wealth of information that enhances our understanding of the genetic basis of both monogenic and complex bone disorders. The insights gained from these studies have wide-ranging applications in clinical practice, including optimizing risk stratification, identifying novel risk factors and disease biomarkers, and improving drug discovery.

As a “proof of concept” approach for demonstrating the potential of integrating deep (musculoskeletal) phenotyping and polygenic scores we have launched the eraSmus medIcal ceNTer skEletal fRagility (SINTER) Study, where we aim at unraveling the causes of skeletal fragility. By combining genetic information, detailed skeletal  measurements, and lifestyle factors (like nutritional and physical activity data), we strive for gaining better understanding of the genetic and environmental factors that affect bone strength. Overall, the SINTER study will provide valuable insights that can help develop more precise treatments and preventive strategies for patients at risk of skeletal fragility, particularly in the presence of concomitant chronic disease. The SINTER Study aims at recruiting 5,650 participants from eight outpatient clinics of Erasmus MC, including: Bone Center (Botcentrum); Diabetology (Diabetologie); Geriatrics (Geriatrie); Healthy Weight Center (Centrum Gezond Gewicht); Nephrology (Nefrologie); Thyroid Center (Schildkliercentrum); Vascular Medicine (Vasculaire Geneeskunde); Mastocytosis (Mastocytose).

Erasmus University Medical Center Rotterdam – Erasmus MC, is a leading research center in Europe and worldwide. Our group within the Genetic Laboratory & Genomics Facility of the Department of Internal Medicine has a strong track record in genomic research and possesses all the necessary infrastructure and resources to conduct the proposed LEGENDARE program. This includes access to computing resources, genomic facilities, and epidemiological cohorts with existing approval from the Medical Ethics Review Committee (METC). Research involving patients will require independent METC approval.