Osteoporosis decreases bone strength owing to loss of bone mass and deterioration in bone microstructure. The maintenance of bone mass and microstructure depends, at least in part, on the signaling and function of osteoblasts. For example, Gi-coupled signaling by G-protein coupled receptors endogenous to osteoblasts has been shown to restrict cortical and trabecular bone formation in female mice [1,2]. This suggests that inhibiting Gi-coupled signaling in osteoblasts may be an effective strategy for the development of anabolic osteoporosis therapies. However, it remains unclear whether inhibiting Gi-coupled signaling improves bone biomechanical behavior. Thus, the objectives of this study were to: 1) quantify the effect of Gi-coupled signaling on bone strength and bone stiffness; and 2) determine the effects of this signaling mechanism on cortical and trabecular microstructure and on the relationship between mechanical behavior and microstructure.

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