Changes in the Ultrastructural Features of Estrogen Deficient Ovine Bone

Osteoporosis is “a skeletal disorder characterised by compromised bone strength predis- posing to an increased risk of fracture” (NIH, 2001). Every second woman and every fifth man will suffer an osteoporotic fracture (Kanis et al., 2000). Of all people that suffer an age-related fracture, the current gold standard of osteoporosis diagnosis, DEXA scanning, misclassifies 80% of them to be non-osteoporotic (Sanders et al., 2006). Bone quantity is easily measured, however, bone strength is an interplay of bone quantity and quality — and the latter is hard to determine. More reliable clinical methods to diagnose osteoporosis are needed as well as widening of our understanding of the underlying mechanisms and of treatment options. Exploring these were the goals of this thesis.

This work used cortical bones from an ovariectomized (OVX) sheep model to study the effects of estrogen depletion and zoledronic acid (ZOL) on bone quality. The usability of Magnet Resonance Imaging (MRI) with novel contrast agents and submillimeter Reference Point Indentation (RPI) to determine parameters of bone quality were explored.

Observation of microcrack propagation showed decreased strength and resistance to frac- ture of OVX bone. The mechanical properties of individual OVX osteons in respect to their age were not different from CON tissue. Novel MRI contrast agents labelled outer and inner surfaces of bone — but microcracks were not detected with the limited reso- lution. OVX periosteal bone showed increased brittleness and easier crack propagation with RPI, while ZOL reversed properties towards control. Improvements were addressed to increase the clinical applicability.

In conclusion, this work illustrates the importance of microstructure in the strength of cor- tical bone as well as the use of clinically applicable submillimeter techniques.