We have reported that the posterior pituitary hormone, oxytocin (OT), known for its effects in inducing parturition, lactation and social bonding, is also a skeletal hormone. Here, we demonstrate that OT plays a key role in enabling maternal skeletal mobilization during pregnancy by enhancing the formation of bone resorbing osteoclasts. Osteoclast formation ex vivo is thus diminished in pregnant mothers with genetic OT-deficiency. OT (/) pups at day E20 also show a defect in trabecular bone. mu CT measurements reveal normal bone volume, but increased trabecular numbers, suggesting that trabeculae in OT (/) pups are hypomineralized. We suggest that OT facilitates intergenerational transfer of calcium ions from a pregnant mother to the pups. (C) 2009 Elsevier Inc. All rights reserved.