INTERACTIONS BETWEEN BONE REMODELING AND MICRODAMAGE IN CANCELLOUS BONE
Matheny, Jonathan Bradford
Increases in bone remodeling impair the mechanical performance of cancellous bone and are associated with the progression of post-menopausal osteoporosis. Bone remodeling is expected to modify cancellous bone strength by changing both bone quantity and bone quality. Bone quality refers to factors that influence the mechanical performance of bone that are not well explained by bone mass. Here, I investigate how bone quality is changed by altering bone remodeling through pharmaceutical treatment and how aspects of bone quality affect the accumulation of tissue damage (microdamage) in cancellous bone. Finally, I investigate how bone remodeling responds to microdamage in a rabbit model of bone marrow lesions (BMLs). First, we examine how treatment with anti-resorptive agents influences the size of individual resorption cavities. We find that anti-resorptive treatment is associated with reductions in the size of resorption cavities in rat vertebral cancellous bone. A reduction in resorption cavity size is hypothesized to decrease stress concentrations generated by the cavity during loading and thereby reduce the likelihood that damage will form nearby. Next, we determine how treatment with sclerostin antibody modifies the trabecular morphology (shape and orientation of individual trabeculae) in a cynomolgus monkey model. We find that sclerostin antibody increases bone formation leading to a conversion of rod-like trabeculae into plate-like trabeculae and increases thickness of both rods-like and plate-like trabeculae leading to an increase in apparent stiffness, as predicted using finite element models. Although microarchitecture was modified, the improvements in apparent stiffness were well explained by changes in bone mass suggesting that treatment changes bone mass and not bone quality. We then examine how resorption cavities and tissue composition influence where microdamage forms and propagates in cancellous bone submitted to cyclic mechanical loading. We find that microdamage formed preferentially in the interior regions of cancellous bone and distant from trabecular surfaces and resorption cavities. The interior regions of trabeculae experience lower stresses but are composed of more brittle tissue. Finally, we investigate the bone remodeling response to microdamage in an in vivo loading model. We find an increase in bone resorption in response to load-induced microdamage. Cancellous bone from within the bone marrow lesion displayed microdamage and increased bone resorption. In summary, tissue composition of cancellous bone influences cancellous bone mechanics. Resorption cavities, while clearly generating stress concentrations do not influence microdamage accumulation. However, when microdamage does form within cancellous bone there is a focal increase in bone resorption.
Biomedical engineering; osteoporosis; Biomechanics; Cancellous Bone; Bone Histomorphometry; Bone Remodeling; Microdamage
Hernandez, Christopher J.
Donnelly, Eve Lorraine; Hayashi, Kei
PHD of Biomedical Engineering
Doctor of Philosophy
Attribution-NonCommercial-NoDerivatives 4.0 International
dissertation or thesis
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 International