Mechanical factors in initial long bone ossification and later functional adaptation [electronic resource]

Our bones constantly adapt to their mechanical environment through a biological response from the womb to the tomb. Mechanobiology, the biological response to mechanical loading, is important for determining various properties of bone such as size and shape. During embryonic development, rapid growth generates significant tension in the periosteum, and tension has previously been shown to lead to bone apposition. In adults, intracortical stresses dominate and increased loading leads to elevated rates in bone apposition. Periosteal tension and intracortical stresses, then, are both experienced by bones, but their influences on bone apposition rates vary over time. This dissertation analyzes how embryonic bone growth rates and adult bone adaptation rates in long bones are related to their respective mechanical environments. The hypothesis that bones grow and adapt at rates corresponding to changes in the mechanical environment is investigated. In the first study, I investigated the mechanical environment of the periosteum during embryonic growth and its relationship to bone growth rates. The specific growth rate, or percent growth per day, was calculated using microCT images taken over embryonic days 11-20. Bones grew faster in length than in circumference during this time. Finite element techniques were then used to analyze the opening dimensions of incisions through the periosteum. Longitudinal and circumferential residual strains decreased from 46.2% to 29.3%, and 10.6% to 3.9%, respectively, during embryonic days 14-20. Residual strains were positively correlated to specific growth rates (p< 0.05). Many studies have investigated bone adaptation in adult mice and rats by applying loads to the long bones, and measuring changes in periosteal cortical bone apposition rates. However, results are difficult to compare because the loading schemes are generally different. The second study presents a theoretical framework for evaluating the mechanical stimulus based on the bone daily strain stimulus, which is a function of loading cycles and bone strains. The daily strain stimulus may act as a single unifying parameter for directly comparing data from existing in vivo experiments. Two approaches were used to determine the periosteal daily strain stimulus necessary for bone maintenance (xi_peri_0) and the strain-cycle weighting exponent (m), which are required to calculate the daily strain stimulus. In the first approach, data from bone maintenance studies were used to calculate xi_peri_0 to be 2793 microstrain/day, and m to be 4.5. In the second approach, strain gage recordings were used to calculate xi_peri_0 to be 1496 microstrain/day, and human bone compressive fatigue properties were used to assign m to be 11.88. Bone apposition rates generally increased with increasing daily strain stimulus, which was consistent with previous theoretical models. The third study provides examples of how the daily strain stimulus may be used to examine the effects of specific loading parameters on bone apposition rates. The effects of inserting periods of rest and frequency were examined. Inserting periods of rest during loading appeared to increase bone apposition rates by approximately 64% compared to continuously loaded bones. Frequency has been previously suggested to be most osteogenic at 5-10 Hz. Using this analysis, an increase in bone apposition rate was also observed at 10 Hz. The results of these studies provide insight into the effects of periosteal tension during embryonic development and intracortical strains during adulthood on bone apposition rates. These findings illustrate how important the mechanical loads experienced by bones and their surrounding tissues are in determining the sizes and shapes of bones.

Keywords: Bioengineering.
Advisor: Carter Dennis R. (Dennis Robert) primary advisor. Thesis advisor
Beaupré Gary Scott advisor. Thesis advisor
Levenston Marc Elliot advisor. Thesis advisor