Bone modeling and remodeling processes occur everyday during one’s life, but change the skeleton in distinct ways. The primary function of bone modeling is to increase net bone mass and shape skeletal structure during growth, while remodeling has an essential role in renew- ing the bone by replacing damaged tissue. Bone modeling primarily occurs during skeletal development in contrast with bone remodeling which occurs throughout life. Interestingly, the principal signal for both processes is believed to be local strain of the tissue. For almost two decades, the theory that microdamage from local bone strains stimulate bone remod- eling has been experimentally investigated by inducing mechanically driven microdamage. Exercise can affect both modeling and remodeling of bone and has a significant influence on bone mineralization. However, few longitudinal studies have been performed during growth to determine if bone modeling occurs to strengthen bone and decrease fracture risk. Further, it is still unclear how mechanical stimuli during exercise result in spatially specific changes in bone. Understanding how bone adapts during growth in terms of bone modeling and remodeling is important to prevent skeletal diseases such as osteoporosis which is charac- terized by a loss of bone mass and quality, and may also be implicated in the etiology of osteoarthritis.
In this thesis, I aimed to (1) characterize changes in bone properties during growth within a single species, (2) identify how bone structural and material properties respond to exercise and postural changes, and (3) investigate how mechanical properties of bone are affected by exercise and posture experimentally.
To investigate longitudinal growth in bone with rats, in vivo microCT scans and gait experiments were performed until 93% of skeletal maturity (n=5, age 8–20 weeks). Cross- sectional properties and tissue density were measured at three different regions (diaphysis, distal and proximal regions of the tibia) and scaling exponents were calculated. Finite- element analyses at each time point was used to confirm the results from the allometric predictions. For the adaptive response of bone to mechanical loading via exercise, healthy juvenile sheep (n=30) have been exercised on a motorized flat or inclined treadmill, while control sheep are not exercised. Joint kinematics data were collected, and bone structural and material properties were evaluated by scanning the medial femoral condyle (MFC) of sheep with microCT. Finally, mechanical testing was performed to obtain the mechanical properties of the subjects (elastic modulus, yield and ultimate stress and strain, toughness, and resilience).
Results from the longitudinal rat study indicate that the structural and material properties of the rat tibial diaphysis are organized to best accommodate bending loads. In addition, the correlations between bone properties and joint angles imply that changes in posture during growth affect bone development in specific regions. From the exercise study, there was a significant effect of exercise on bone during growth, especially in flat group. Exercise increased subchondral and trabecular bone properties, and trabecular changes were depth- dependent. Finally, increases in elastic modulus, yield and ultimate stress in all exercised bone compared to controls demonstrated the effect of exercise on bone strength. Flat exercise had more effects on all mechanical properties except for strains than incline exercise, as expected given the broader increases in structure and density. Strong correlations between bone density versus elastic modulus and yield stress versus elastic modulus may lead to prediction of bone strength from different types of exercise.
Taken together, these results indicate that postural changes affect bone acclimatization to mechanical loading from the longitudinal study, and intentionally induced loading from exer- cise during growth resulted in enhanced structural and material properties, and mechanical strength of bone. The present method of analysis for three-dimensional site-specific changes in structural and material properties of bone has great potential as a clinical prediction model of the bone growth from specific mechanical loading, and can be applied to develop exercise strategies aimed to improve bone properties.