3D In Vivo Bone Dynamic Imaging of PTH’s Anabolic Action

Aging shifts bone remodeling toward a negative balance between bone formation and resorption, causing bone loss and increased fracture risk. Anti-resorptive agents are commonly used to inhibit bone resorption and stabilize bone mass. While they are effective to prevent further bone loss, there is also a great need for anabolic agents which can reverse bone deterioration and regain lost skeletal integrity. Intermittent parathyroid hormone (PTH) treatment is the only FDA-approved anabolic treatment for osteoporosis, which greatly stimulates bone formation. Combined therapy of anti-resorptive drugs, such as alendronate (ALN), and PTH have been proposed and are expected to further stimulate bone formation. However, studies show conflicting results regarding the effectiveness of combined treatments: some have reported the addition of ALN to impair PTH function [1, 2], while others suggest an improvement over PTH monotherapy [3, 4]. The first objective of this study is to document the immediate changes of individual trabecular structures due to PTH and combined therapy within 12 days using in vivo micro computed tomography (μCT). As PTH is typically prescribed for 1 to 3 years to osteoporotic patients, a treatment of 12 days for rats (approximately equivalent to one year of human life) may be more clinically relevant than long-term treatment studies on rats. The secondary purpose of this study was to gain insight into the mechanism of combined versus PTH treatments through a bone dynamic imaging strategy to track events over an individual remodeling site. We hypothesized that PTH and combined treatments would immediately enhance bone formation on the trabecular surface.