PROJECT SUMMARY Individuals with neurodevelopmental disabilities (NDDs) have unmet healthcare needs and heightened susceptibility for skeletal fragility and non-trauma fracture (NTFx) throughout their lifespan, resulting in greater risk for early development of chronic diseases and early mortality. There is a fundamental gap in the understanding of skeletal pathology, burden of NTFx, and clinical care needed to prevent and manage skeletal fragility for these vulnerable adult populations. Continued existence of this gap represents a major public health issue because the adult population with NDDs is growing, and poorly managed healthcare could lead to a disproportionate rise in the disease burden attributable to adults with NDDs. The long-term goal is to identify and address unmet healthcare needs to improve healthful aging for individuals with NDDs. The objective of this multi-level study is to address fundamental knowledge gaps in order to improve clinical care for skeletal fragility and to optimize clinical trial design to reduce the NTFx burden for adults with NDDs. Aim 1 will identify risk factors for NTFx and determine the post-NTFx burden of diseases and mortality among a large, heterogeneous sample of adults with and without NDDs by leveraging nationwide private and public administrative claims data from 2012-2019. This information will be used to inform intervention strategies and determine important health- related outcome measures to be used as benchmarks of success for future clinical trials. Aim 2 will determine causes of NTFx among a clinical sample of adults with NDDs by leveraging electronic medical records. This information will be used to inform intervention strategies for future clinical trials. In Aim 3, mixed methods will be used to develop and then administer a survey to gauge patient awareness on the importance of NTFx prevention on their overall health and function, willingness to participate in NTFx prevention programs (e.g., clinical trial), and barriers and facilitators that may impact clinical trial participation. This information will be used to identify obstacles, opportunities, and solutions to design successful clinical trials to reduce the burden of NTFx specific to the needs of these complex patient groups. The research is clinically innovative because it will challenge the current paradigm regarding NTFx assessment and evaluation, which is typically focused on older adults and postmenopausal women. The research is also innovative because of the use of a complementary, multi-level research design for information gathering across national, clinic, and patient levels to optimize clinical care and clinical trial design. The research is significant because it is expected to improve clinical care, increase public health awareness about the burden of skeletal fragility, and optimize clinical trial design to reduce the NTFx burden for these underserved populations. The purpose of this research is aligned with the purpose...