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Bone is a dynamic organ that from the early stages of development defines an organism's form and function and responds to the external environment, a process that continues as the organism grows and persists even once maturity is reached. The formation, growth, and integrity of bone are co-ordinated and maintained throughout life via the finely tuned actions of osteoblasts and osteoclasts, with disruption in this balance leading to skeletal abnormalities and bone disease. The precise complement of mechanisms balancing these actions is not fully known, although several regulatory systems are known to be involved and current treatments for bone disease target these systems. The actions of purinergic signaling in bone have come to light over the past 20 years or so, but previously the emphasis was largely placed upon G-protein coupled P2Y receptors. This article details the current status of P2X receptors in bone, mainly focussing on the P2X7 receptor for which the most compelling evidence exists for its regulatory role in bone. The contribution of other P2X receptors to bone biology and future directions are also discussed.WIREs Membr Transp Signal 2012, 1:221–227. doi: 10.1002/wmts.26For further resources related to this article, please visit the WIREs website.