In keeping with their important roles in bone, P2rx7-/- and P2ry2-/- mice have been shown to exhibit severe bone phenotypes, with P2rx7-/- mice demonstrating significant deficiency in bone mineral density and truncated response to mechano-adaptive loading [27,28], and P2ry2-/- mice similarly experiencing osteopenia and altered mechanotransducive responses [29]. Here, P2RY2 is linked to Osteopenia.