A considerable subset of patients with early-onset low bone mineral density (BMD) also presents with skeletal dysplasia and/or osteoarthritis. As an integral part of ProBone, we will therefore perform an in-depth orthopedic examination of affected patients, including high-resolution musculoskeletal imaging, synovial analysis, and application of physician-based and patient-reported outcome measures. A multiscale histomorphometric and molecular analysis is employed on intraoperatively obtained tissue biopsies. To provide a more detailed mechanistic understanding of osteochondral pathologies, we will also differentiate human induced pluripotent stem cells (hiPSCs) into chondrocytes. Finally, in close collaboration with other ProBone groups, we will study joint phenotypes and osteochondral interactions in several genetically modified mouse models of different types of osteogenesis imperfecta, lysosomal storage disorders, and hypophosphatasia. With the knowledge gained, we aim to decipher the influence of specific low BMD gene variants on endochondral ossification and cartilage biology, and to develop more individualized orthopedic treatments for affected patients.

Department of Trauma Surgery and Orthopedics

Department of Orthopedics