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Leveraging genomic discoveries and skeletal phenotyping to improve osteoporosis patient care

Project description

Understanding bone fragility to improve osteoporosis patient care

Fragility fractures are the clinical manifestations of osteoporosis. The EU-funded LEGENDARE project will study the mechanistic pathways leading to bone fragility by implementing a novel holistic approach to see, touch and analyse the human skeleton. Obtaining 3D X-ray scans of the entire skeleton as a unified organ, the project will shed light on hidden relationships across bone compartments. Integrating imaging, bone quality assessments and genomic discoveries in the form of optimised polygenic risk scores, LEGENDARE will translate its discoveries into meaningful clinical strategies for stratifying patients with skeletal diseases. With the use of artificial intelligence, newly collected data on thousands of participants and patients will guide the (molecular) redefinition of skeletal disease.


Osteoporosis is a silent, systemic skeletal disease leading to fragility fracture. While the deleterious consequences for the individual, their families and society are well established, the causes of the disease remain elusive. Despite exhaustive clinical, epidemiological and genomic research, scarce understanding of the complex underlying disease mechanisms leading to bone fragility has hindered the improvement of clinical care. This LEGENDARE programme aims to implement a holistic integrative approach directed at discerning the underlying mechanistic pathways leading to bone fragility. The approach seeks translating genomic and imaging discoveries into meaningful clinical strategies to stratify risk; re-evaluate treatment indication; and ultimately, redefine (molecular) disease classification of patients with osteoporosis and other skeletal diseases. LEGENDARE will progress beyond the state-of-the-art by integrating genomic information from thousands of loci (genome regions) associated with musculoskeletal traits and other diseases, into “optimized” polygenic risk scores providing novel biological insight about skeletal disease. Skeletal research will be brought to a new level by enriching skeletal imaging with BIG DATA obtained with advanced whole-body EOS 3D X-rays. Approaching the whole skeleton as a unified organ will allow the unprecedented study of hidden relationships across bone compartments. Further, using artificial intelligence approaches, the complexity of the skeletal system will be modelled, integrating genomic, imaging and clinical data across epidemiological cohorts and patient settings. LEGENDARE will deliver knowledge on fundamental processes regulating skeletal fragility, unveiling new strategies for translational exploitation leading to improved clinical outcomes of osteoporosis patients. Discoveries will hold wider significance through potential spinoffs able to mitigate the societal impact of other diseases surging with bone fragility.


Net EU contribution
€ 2 499 995,00
Dr molewaterplein 40
3015 GD Rotterdam

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West-Nederland Zuid-Holland Groot-Rijnmond
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00

Beneficiaries (1)