Quantifying Sex-Specific Musculoskeletal Adaptations to Wheelchair Use in Childhood and Adolescence - Project Summary Up to 70% of manual wheelchair users experience shoulder pain, and as many as 90% develop pathologies like rotator cuff tendinopathies and glenohumeral instability. This can have profound negative effects on quality of life through reduced participation in everyday activities and can increase the lifetime risk of secondary medical conditions like cardiovascular disease through reductions in physical activity. Yet, clinical guidelines for the preservation of upper limb function in manual wheelchair users are only applicable to users with adult-onset disabilities, and do not account for sex. As a result of this gap in knowledge, pain begins in adolescence and increases significantly during the transition to adulthood in users with pediatric-onset disabilities. In addition, the increase in pain during this period is far greater for females than males, even when accounting for years of wheelchair use. Our central hypothesis is that this sex-related divergence in pain is precipitated by sex-specific musculoskeletal adaptions to wheelchair use in childhood and adolescence. During this period of life, females experience far lower upper extremity muscle and bone growth velocities and a shorter window in which to adapt to wheelchair use. Moreover, musculoskeletal adaptations are driven by the mechanical demands one experiences. We have evidence that wheelchair use is far more demanding of upper extremity musculature for females than males, even when accounting for individual size. We will test our central hypothesis by establishing the relationships between sex-specific adaptations to (Aim 1) glenohumeral muscle morphology, (Aim 2) scapula shape, and (Aim 3) scapular kinematics and pain, while accounting for years of wheelchair use and arm dominance. Our approach will leverage bilateral magnetic resonance imaging to determine the influence of sex and wheelchair use in childhood and adolescence on the balance of glenohumeral musculature and the shape of the glenoid and acromion, advanced biomechanical modeling to determine adaptations to scapular kinematics at rest and during humerothoracic elevation and wheelchair propulsion, and patient-reported outcomes to quantify shoulder pain and pain interference. We expect to reveal sex-specific musculoskeletal adaptations to wheelchair use in childhood and adolescence associated with pain that can be immediately addressed with established rehabilitation paradigms including strengthening exercise and motor training. Moreover, the results of the proposed research will provide foundational knowledge for the development of sex-specific wheelchair use guidelines for pain prevention. Finally, we expect to uncover potential mechanisms underlying the development of glenohumeral instability and rotator cuff pathologies. By determining the etiology of shoulder pain with consideration for sex, we hope to increase equity in the prevention and rehabilitation of secondary musculoskeletal conditions associated with manual wheelchair use.