Periodic Reporting for period 2 - LEGENDARE (Leveraging genomic discoveries and skeletal phenotyping to improve osteoporosis patient care)
Okres sprawozdawczy: 2023-05-01 do 2024-10-31
Bone fragility is a significant health issue that often goes beyond the traditional understanding of osteoporosis, which is diagnosed through the measurement of bone mineral density (BMD). Many fractures occur in individuals with BMD higher than the osteoporosis threshold, suggesting that factors other than low bone density contribute to bone weakness. Current treatments for improving bone health often fail to prevent further fractures, leaving patients vulnerable even after initial injuries. Despite extensive clinical, epidemiological, and genetic studies, our limited understanding of the disease's complex mechanisms has hindered better care. Fractures due to fragile bones can lead to a substantial decrease in quality of life, causing chronic pain, loss of mobility, and a reduced ability to perform everyday activities. These fractures are also associated with increased mortality, especially in older adults, where a broken hip or spine can lead to severe health complications and a higher risk of death. Moreover, the economic burden of bone fragility is large, with healthcare costs increasing due to hospitalizations, surgeries, and long-term care requirements. This financial strain extends beyond the healthcare system to families and caregivers who often bear the costs of rehabilitation and support. While environmental components like lifestyle (e.g. physical activity and nutrition) play an important role, bone fragility is also importantly determined by the genetic make-up of individuals. Despite this awareness, extensive genetic research revealing genetic variants that influence bone strength, is not yet being applied in clinical settings to improve patient care. Understanding and addressing bone fragility is therefore essential to improve individual well-being, reduce mortality rates, and alleviate the economic pressures on both families and healthcare systems.
This project aims to improve care for indiviuals at risk of bone fragility, by using a comprehensive approach to understand what causes bone fragility. This involves combining via machine learning approaches, genetic discoveries, with 3D x-ray imaging and “touching” the bone via microidentation, and translate findings into practical clinical strategies to assess risk, understand pathophysisology and redefine how we classify bone diseases.
This project aims to improve care for indiviuals at risk of bone fragility, by using a comprehensive approach to understand what causes bone fragility. This involves combining via machine learning approaches, genetic discoveries, with 3D x-ray imaging and “touching” the bone via microidentation, and translate findings into practical clinical strategies to assess risk, understand pathophysisology and redefine how we classify bone diseases.
LEGENDARE has incorporated in its program an EOS Edge medical imaging device used for the first time exclusively for musculoskeletal research in population-based and clinical studies. This EOS Edge system was successfully installed, and data collection has begun, with 150 individuals of the Rotterdam Study having been already scanned. Research technicians and staff received extensive training for image acquisition and processing. Starting in September 2024, 3D parameters will be extracted from post-processing images to evaluate known and novel determinants of skeletal health, comprehensively. This data will enhance our understanding of factors like balance, fall risk, and anatomical structures. Additionally, individuals underwent DXA, pQCT, mechanography, and dynamometer assessments. Our core team trained in machine learning techniques has begun analysing existing radiographs from the Rotterdam Study, paving the road for future analyses using EOS Edge images. Progress has been made in designing a clinical study to assess skeletal fragility and implement genomic tools. We refined the study setting to focus on patients with genetic susceptibility at developing bone fragility across various outpatient clinics in collaboration with diverse medical specialties. Contacts with clinicians were established, and ethics applications are under review. The study will recruit 5,250 patients, with genetic information used to invite 1500 selected individuals to undergo detailed bone fragility measurements.
Within LEGENDARE we are pioneering a new method to assess the entire skeleton while standing, providing a more natural and complete functional picture of the skeleton. Unlike traditional imaging, which is done lying down, this approach helps us understand how the skeleton supports the body during everyday activities in the form of a unified organ. We will combine this visualization of the skeleton with an assessment of material quality by “touching” the bones. Making use of advancements in genetics, we will also consider the contribution of the “make-up” of individuals to their susceptibility for skeletal fragility. In addition, we will employ artificial intelligence methods to be able to integrate these multifaceted data and sort out the complex mechanisms leading to skeletal fragility in health and diseases states. LEGENDARE will expand the knowledge on assessing, preventing and treating skeletal fragility through establishing new research collaborations. LEGENDARE will generate new insights into the biomechanics and structural integrity of bones under normal conditions. Within clinical settings, LEGENDARE will also offer proof-of-concept validation for implementing studies using genetic information in their study design as done with the SINTER study in Erasmus MC. The SINTER study is the largest of its kind, enhancing our ability to understand genetic influences on skeletal fragility, but also enabling other clinical researchers to use this cost-effective and statistically powerful method in their studies on other diseases