Mechanical adaptation of trabecular bone formation in vivo.

Abstract

The global objective of this dissertation was to quantify the adaptive response of newly-formed trabecular bone to a controlled in vivo mechanical stimulus. The hydraulic bone chamber (HBC) implant was introduced as a simple, yet versatile experimental model of trabecular bone formation and adaptation. The HBC was designed to be implanted into metaphyseal trabecular bone, allow repeated biopsies through a minimally invasive surgical procedure, and provide a substantial volume of extracted tissue for subsequent analysis. The unique feature of this model was its ability to pressurize an internal piston and thereby apply a controlled compressive force to a developing core of trabecular bone within the chamber. This feature was utilized to test the hypothesis that the cellular activity, trabecular microstructure, and mechanical properties of newly-formed trabecular bone would be altered by a daily intermittent compressive mechanical load. As a whole, this dissertation demonstrated that trabecular bone formation is highly sensitive to in vivo mechanical loading. The adaptive mechanisms included thickening and connecting of the trabecular microstructure which was associated with a 600% increase in the compressive apparent modulus of HBC biopsies. Within the 12 week loading period, a concurrent increase in trabecular-level modulus, calculated using digital image-based microstructural finite element modeling, was not detected. Regardless of loading conditions, the average HBC tissue trabecular-level modulus remained less than 1.0 GPa, significantly lower than that measured for mature population trabecular bone from the same region (3.0 GPa). Cellular activity within HBC tissue was also influenced by the introduction of an in vivo mechanical stimulus. The percentage of trabecular surfaces covered by osteoblast cells expressing the matrix precursor type I procollagen was significantly increased after only a few days of mechanical loading. In conclusion, a new in vivo experimental model was developed and applied to evaluate cellular and microstructural mechanisms of trabecular bone formation and adaptation. An improved understanding of the relationship between trabecular bone structure and its functional mechanical environment has relevance to the treatment of a variety of clinical conditions including skeletal development disorders, bone grafting, fracture healing, total joint replacement, and osteoarthritis.