The effects of age and IGF-1 availability on the recovery of bone mineral density after lactation

Lactation causes depletion of the maternal skeleton due to calcium resorption. Once lactation ceases, repair is achieved through bone remodeling, which involves communication between bone cell populations including bone-resorbing osteoclasts and bone-forming osteoblasts. Communication is mediated by factors such as insulin-like growth factor 1 (IGF-1), whose bioavailability is controlled by pregnancy-associated plasma protein A2 (PAPP-A2), which frees IGF-1 by cleaving of insulin-like growth factor binding protein 5 (IGFBP-5). The objectives of this study are to determine whether PAPP-A2 is involved in the recovery of bone after lactation and to test whether recovery is affected by age, using mouse models. PAPP-A2 knockout and control mice were bred at the ages of two, five and seven months and culled at wean or three weeks after to determine what bone traits were affected by breeding. Femurs were measured by microCT and blood was collected for measurement of IGF-1 and IGFBP-5. There was a significant decrease of trabecular BV/TV and trabecular thickness in bred mice compared to nulliparous controls. Trabecular spacing was not affected by breeding. Cortical bone area fraction and thickness was lower in lactating mice. Three weeks after the end of lactation, there was a partial recovery of cortical bone area fraction and cortical thickness, while trabecular bone did not recover. Deletion of Pappa2 did not affect bone recovery. Age affected the recovery of cortical thickness, which was impaired in mice at the age of five months compared with two or seven months. These results highlight the importance of age at reproduction for evaluation of bone recovery after lactation.