Background:The contribution of endogenous norepinephrine (NE) to skeletal homeostasis is unclear. Results: Bone forming cells, not only neurons, express the norepinephrine transporter (NET), and blockade of extracellular NE clearance causes alterations in bone homeostasis. Conclusion: NE clearance by NET is a component of the homeostatic machinery by which sympathetic nerves and osteoblasts control bone remodeling. Significance: NET blockers may increase fracture risk.