Regulation of Bone Metabolism During Pregnancy, Lactation, and Post-Weaning

Pregnancy and lactation place significant demands upon mammals to supply calcium to the fetus and neonate, respectively. Despite a similar magnitude of calcium demand incurred by pregnancy and lactation, the adjustments made in each of these reproductive periods differ significantly. Upregulation of intestinal calcium absorption dominates during pregnancy, whereas the skeleton rapidly resorbs during lactation in order to provide calcium to milk. The magnitude of loss is 5-10% of skeletal mineral content during 6 months of lactation in humans, and a 25-55% loss during 3 weeks of lactation in rodents. In all mammals, the skeletal mineral content is fully restored after weaning. Novel mechanisms appear to be invoked to upregulate intestinal calcium absorption independent of calcitriol during pregnancy. An elegant interaction between breast, brain and bone programs the skeletal resorption that occurs during lactation. The post-weaning recovery of the skeleton is also regulated by novel mechanisms that do not require the known calciotropic hormones, but do involve upregulation of Wnt signaling. Identifying the mechanisms that stimulate the skeleton to restore itself after lactation may lead to new approaches to treat women, men, and children with osteoporosis or skeletal fragility.