Dissertation Date: June 5, 2026
Osteogenesis imperfecta (OI) is a rare genetic disease primarily affecting the production of collagen in the body, resulting in bone fragility, skeletal deformity, muscular weakness, and short stature, among other traits related to connective tissue weakness. Type I is the mildest and most common form, making up about 90% of cases. Bone abnormalities and muscle weakness in OI impair mobility and gait, reflected in slower walking speed, longer double support time, and reduced ankle plantarflexion moment and power generation during stance. Although limited research has examined physical training in OI, regular exercise has been shown to improve aerobic capacity, muscle force, and quality of life. However, because OI bone has impaired mechanical and material properties, it remains unclear how strength related increases in muscle forces may influence bone mechanical stress in OI. The objective of this dissertation was to quantify changes in strength and resulting injury risk during gait using musculoskeletal simulation and finite element (FE) analysis.
Aim 1 simulated changes in plantarflexor strength through adjustment of maximum isometric force (MIF) during the stance phase of healthy and OI gait using a musculoskeletal model. Simulations quantified lower extremity muscle forces, joint reaction forces, and joint reaction moments at five different strength levels. Results demonstrated significant increases in the gastrocnemius and tibialis anterior peak muscle force and significant decreases in the soleus peak muscle force between each strength level in OI and age-matched control children. Changes in MIF also affected anterior-posterior hip and knee joint reaction forces, and vertical knee joint reactions forces in the OI population. Simulation outputs help further characterize movement in children with OI, providing guidance in rehabilitative efforts targeting specific muscle groups.
Aim 2 utilized musculoskeletal simulation outputs from Aim 1 to evaluate how changes in muscle force and joint loading affect mechanical stress in the femur during the midstance phase of gait. Subject-specific femur models for control children and children with OI were developed. OI models incorporated mild lateral bowing and deficient material properties associated with OI type I bone. Results highlighted areas of high stress at the gluteus medius insertion, femoral neck, and lateral diaphysis in both groups.
Aim 3 used musculoskeletal simulation outputs from Aim 1 to evaluate how changes in muscle force and joint loading influence tibial mechanical stress during midstance of gait. Similar to Aim 2, subject-specific control and OI tibia models were created and assessed using current bone properties from literature and physiological boundary conditions, improving on previous OI tibia models. High‑stress regions were identified primarily along the anterior tibial diaphysis.
In both FE models, there were minimal changes in stress between strength levels for each subject. In the femur models, linear regression analysis showed that, in controls, stress at the femoral neck and gluteus medius insertion were strongly correlated with height, weight, walking speed, and age, whereas diaphyseal stress correlated only with age. In the OI group, height and weight were correlated with diaphyseal and neck stress, and age correlated with stress at all three femoral sites. In the tibia, diaphyseal stress correlated only with age in the OI group.
Results from Aim 2 and Aim 3 help to characterize the impact of plantarflexor strength on stress in the femur and tibia using FE analysis, underscoring the importance of patient-specific models in determining fracture risk. The combination of musculoskeletal modeling and FE analysis provides a realistic framework for understanding how changes in muscle and joint loads influence bone stress. Together, these findings can help guide future clinical strategies aimed at reducing fracture risk, improving strength, and prescription of activities in the OI population.
