Osteoporosis is a disease that affects nearly 75 million people worldwide. It occurs due to skewed activity of osteoblasts, which form new bone, and osteoclasts, which breakdown old bone. The disease is characterized by decreased bone mineral density (BMD), degradation of the trabecular architecture and increased fracture risk.

Prevention of bone loss by inhibition of osteoclast-mediated bone resorption appears to be the major mechanism for fracture risk reduction and increased BMD, seen with bisphosphonates (BPs) in osteoporosis. However, recent studies have shown that BPs may negatively affect bone quality. The goal of this dissertation was to determine the effect of bisphosphonate-treatment on the quality of existing and newly formed tissue. Understanding how bone quality might be altered will help to understand the long term affects of bisphosphonate-treatment.

Chemical composition of bone and mineralizing osteoblasts was determined using Fourier transform infrared imaging and matrix morphology was examined using nano-transmission x-ray tomography. We found that, while microdamage was not accumulated in areas of increased mineralization, formation of microcracks led to changes in the mineral stoichiometry and collagen cross-links. Microdamage accumulation and changes in bone composition due to microcrack formation may lead to changes in post-yield mechanical properties and increased fragility.

Further, we found that the rate of collagen deposition and mineralization were temporarily slowed by risedronate-treatment. The morphology of the mineral formed by the risedronate-treated cells was not altered. This paired lag in activity appears to be due to decreased function of osteoblasts cells, caused by BP-treatment.

While these results are difficult to directly extrapolate to the clinical setting, the concept that chemical composition and structure can be directly linked to mechanical properties of bone remains important. Therefore, further studies, specifically determining if BPs have long-term effects on osteoporotic patients needs to be undertaken.