Poster Presentation: Lindsey Young

ABSTRACT

Effects of Anti-Resorptive Therapy, PIEZO Agonist, and Loading on Aged Tibial Bone

¹Lindsey A. Young, ¹Vineel Kondiboyina, and ¹Sandra J. Shefelbine

¹Northeastern University

Osteoporosis is a major health challenge that primarily impacts aging populations. Current treatments focus on utilizing bisphosphonates, such as Alendronate, due to their ability to reduce bone resorption. However, its ability to stimulate new bone formation is limited and does not address the cause of bone mass loss. Piezo1 agonists, such as Yoda2, have been shown to activate mechanosensing pathways in bone and increase cortical bone properties in aged bone. However, the combination of a bisphosphonate, a Piezo1 agonist, and mechanical loading has not yet been investigated.18 month old female C57BL/6 mice were divided into four groups: Control (Vehicle), Yoda2 only, Alendronate only, and a combination of Yoda2 and Alendronate. Each group were given a series of intraperitoneal injections 5 days a week for 4 weeks. Mice also had their right hindlimbs mechanically loaded 3 days a week for the last two weeks. Tibias were scanned with a microCT and cortical bone properties were quantified using BoneJ. We examined the effects of drug dosing and loading by comparing the cross-sectional area, cortical thickness, and moments of area along the length of the diaphysis. Mice injected with Yoda2 had a significant increase in cross-sectional area in the loaded limb, compared to the contralateral control limb at approximately 30% of bone length. Loaded tibia of mice administered with a combination of Alendronate and Yoda2 had significantly greater CSA than unloaded limbs of Yoda2 mice and vehicle mice at approximately 30% of bone length. The combined effects of Yoda2 and Alendronate may increase the impact of loading on osteocyte mechanosensing. Future work investigating the effects of combining a bisphosphonates, Piezo1 agonist, and loading will measure the effects on bone strength and differentially expressed genes in the femurs of these mice.