More than bones: Expanding the understanding of rare monogenic variants causing early-onset osteoporosis with emphasis on osteogenesis imperfecta

This thesis investigates the extra-skeletal manifestations of osteogenesis imperfecta (OI), aiming to deepen the understanding of how genetic variants affecting collagen type I can lead to a wide range of health complications, including cardiovascular, dental, respiratory, and other systemic issues. Through population-based studies, healthcare utilization patterns are analyzed among Dutch individuals with OI and those with rare monogenic variants causing early-onset osteoporosis, such as LRP5, PLS3, and WNT1. The analyses reveal higher rates of hospital admissions and medication use in these individuals compared to the general Dutch population. Additionally, this thesis focuses on dental and cardiovascular abnormalities in OI by incorporating literature reviews and pathology research. It also introduces innovative techniques, such as polarization-sensitive optical coherence tomography (PS-OCT) for examining ocular tissue and forced oscillation techniques (FOT) for evaluating lung function. These advanced methods are assessed for their potential to provide deeper insights into how OI affects tissues beyond the skeletal system.