During lactation, the large transfer of calcium from the mother to the milk is largely sourced from the maternal skeleton. The mechanism controlling calcium efflux from the skeleton during lactation is not fully understood, however is thought to be mediated, in part, by PTHrP. Circulating levels of calcitonin are also elevated during pregnancy and lactation, supporting the notion that calcitonin, via its inhibitory actions on osteoclasts, opposes the actions of PTHrP, thereby protecting the maternal skeleton from excessive resorption. In support of this concept, calcitonin and calcitonin gene related peptide null mice exhibit greater losses in bone mineral content compared to wild-type littermates following lactation, which is prevented by treatment with calcitonin1. To further investigate the mechanism by which calcitonin exerts its protective effects, we assessed the maternal skeleton and calcium homeostasis of our global calcitonin receptor knockout mice (global-CTRKO) and control littermates at the end of lactation (P21), and in their offspring at 6 weeks of age. The most striking observation was an increase in osteocytic, but not osteoclastic, osteolysis in global-CTRKO mice at the end of lactation, which was accompanied by a marked increase in their serum levels of calcium. This provides the first evidence for a physiological role of the CTR to protect the maternal skeleton during lactation by a direct action on osteocytes to inhibit osteolysis. The skeletal development of the offspring was unaffected by maternal CTR deletion, however, serum calcium levels were elevated in offspring of Global-CTRKO mothers compared to offspring of control mothers for the same PTH range. This may reflect a change in the set point for the ionised calcium levels for PTH secretion in the absence of maternal CTR. Collectively, these findings represent a significant advance in our understanding of the physiological role of calcitonin and the CTR during lactation when the demand for calcium is high.