Repository logo

The Development Of A Cortical Bone Turnover Model: Parathyroid Hormone Effects In The Rabbit



Journal Title

Journal ISSN

Volume Title






Degree Level



Osteoporosis (OP) is a disease of progressive bone loss that is intimately linked with bone remodeling, a lifelong process of turnover essential for the maintenance of bone microarchitecture. Remodeling involves processes of coupled bone resorption and formation, carried out by complex cellular groupings known as basic multicellular units (BMUs). Imbalances in remodeling, where bone resorption exceeds formation, leads to elevations in cortical porosity and an increased risk of OP. Understanding the spatio-temporal coordination of BMUs is the key to elucidating the mechanisms underpinning cortical bone loss associated with OP and developing therapeutic approaches aimed at improving the balance between BMU phases to minimize bone loss. Much of the research on this subject has been largely theoretical or in silico thus far due to the lack of direct empirical evidence. Combining the use of high-resolution synchrotron based micro-computed tomography (micro-CT), a powerful imaging tool capable of characterizing cortical porosity in three-dimensional (3D) space, with the appropriate animal model has the potential to directly track individual BMUs and assess their behaviours in vivo. Rabbits are suitable model systems since they are the smallest laboratory animals to exhibit cortical bone remodeling like humans, however, remodeling rates in their cortices are generally low and approaches aimed at increasing remodeling have largely focused on trabecular bone. Therefore, there exists a need to develop an operationally effective cortical bone model given the growing recognition of the role cortical bone microarchitecture plays in bone loss and fragility in OP. The primary aim of this thesis was to establish a cortical porosity model in the rabbit using parathyroid hormone (PTH), a known inducer of cortical remodeling at intermittent levels. The experiment described in this thesis is presented as one aspect of a larger study characterizing numerous rabbit-based models of cortical bone loss (ovariectomy and glucocorticoid induced), all of which are compared to a control. After one month of intermittent PTH administration, cortical bone microarchitectural changes in the distal tibiae of rabbits were assessed ex vivo using micro-CT at a resolution of 10 μm and dynamic histomorphometry. Trabecular bone microarchitecture of the proximal tibial epiphysis was assessed secondarily. Results indicated that cortical porosity was substantially elevated in PTH rabbits relative to controls, and this was associated with increases in remodeling rate and cortical pore size. Despite bone losses intracortically, bone formation was evident on endosteal and periosteal surfaces of the tibiae and the rate of new bone deposition was increased in BMUs. Furthermore, a pattern of bone gain was observed in the proximal tibial epiphysis indicated by changes in micro-CT derived trabecular microarchitectural parameters. Notably, remodeling induced by PTH appeared to be distinct from that of the other rabbit-based models of bone loss in this larger study, with regards to cortical porosity and trabecular bone structural changes, warranting further investigations into these intriguing PTH-driven effects. Overall, the PTH rabbit model provides an effective and novel platform for developing future mechanistic studies aimed at testing a number of hypotheses directly related to bone remodeling regulation, which would ultimately enhance our understanding of the complex and dynamic nature of cortical bone in health and disease.



Bone, Osteoporosis, Rabbit



Master of Science (M.Sc.)


Anatomy and Cell Biology


Anatomy and Cell Biology


Part Of