Elevated Bone Remodeling
Osteoporosis is a disease characterized by low bone density, which can lead to an increased risk of bone fractures1. Osteoporosis is closely linked to bone remodeling2, an adaptive process which maintains bone tissue integrity throughout one’s lifetime3. This process is carried out by specialized groups of bone cells known as basic multicellular units (BMUs) which dictate the processes of coupled bone breakdown and bone formation.3 During osteoporosis, this bone turnover rate accelerates and bone remodeling is shifted towards greater bone resorption than formation, resulting in cortical bone loss2. Because osteoporosis arises from this imbalance in bone remodeling processes, strategies to prevent or reverse osteoporosis must aim to improve
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Skeletally mature New Zealand rabbits serve as excellent models to investigate BMU behaviour since they naturally exhibit cortical bone remodeling.4-6 Elevated bone remodeling will be induced through the administration of parathyroid hormone (PTH) injections, as PTH is known to have well documented effects in accelerating cortical bone turnover.7-9 After 4 weeks of injections, the animals will be euthanized and the right tibiae of each animal will be dissected and removed for analysis. Analysis of cortical bone microarchitecture will be carried out through 3D imaging and histomorphometry, both of which will quantitatively assess bone remodeling in each tibiae10-13. Micro- computed tomography (CT) is an effective and non-invasive means to resolve fine cortical bone porosity and therefore will be used to visualize and quantify BMUs in 3D.10-12 Activation frequency, the number of BMUs present in a given volume of bone, will be calculated from these results14. Histomorphometry will be performed to further examine BMU progression in 2D and confirm the results obtained in 3D. The bone labelling fluorochrome calcein, which binds to newly formed bone, will be administered to rabbits at two time points during the study for the assessment of bone formation over time.13 Together, these techniques provide valuable information of how PTH affects the coordination of bone remodeling events and BMU behaviour in cortical bone, keys in understanding bone remodeling homeostasis. This research is in parallel with a recently funded CIHR Catalyst Grant by our group (Cooper) investigating similar parameters in a combined ovariectomy/glucocorticoid rabbit
Skeletally mature New Zealand rabbits serve as excellent models to investigate BMU behaviour since they naturally exhibit cortical bone remodeling.4-6 Elevated bone remodeling will be induced through the administration of parathyroid hormone (PTH) injections, as PTH is known to have well documented effects in accelerating cortical bone turnover.7-9 After 4 weeks of injections, the animals will be euthanized and the right tibiae of each animal will be dissected and removed for analysis. Analysis of cortical bone microarchitecture will be carried out through 3D imaging and histomorphometry, both of which will quantitatively assess bone remodeling in each tibiae10-13. Micro- computed tomography (CT) is an effective and non-invasive means to resolve fine cortical bone porosity and therefore will be used to visualize and quantify BMUs in 3D.10-12 Activation frequency, the number of BMUs present in a given volume of bone, will be calculated from these results14. Histomorphometry will be performed to further examine BMU progression in 2D and confirm the results obtained in 3D. The bone labelling fluorochrome calcein, which binds to newly formed bone, will be administered to rabbits at two time points during the study for the assessment of bone formation over time.13 Together, these techniques provide valuable information of how PTH affects the coordination of bone remodeling events and BMU behaviour in cortical bone, keys in understanding bone remodeling homeostasis. This research is in parallel with a recently funded CIHR Catalyst Grant by our group (Cooper) investigating similar parameters in a combined ovariectomy/glucocorticoid rabbit