Skeletal changes during lactation and after weaning in osteocyte-specific sclerostin overexpressed mice.

Abstract

Lactation inevitably leads to a state of rapid bone loss; however, maternal bone undergoes rapid remineralization after weaning. Sclerostin, encoded by the gene SOST, is exclusively secreted from osteocytes and plays important roles in bone remodeling. However, there are few studies about the effect of sclerostin during lactation and weaning on bone microstructures. Therefore, we conducted the study to demonstrate any possible association of sclerostin with bone metabolism and skeletal changes during lactation and after weaning. We analyzed bone mineral density (BMD) by dual-energy X-ray absorptiometry at the spine and femur, bone microstructure by micro-computed tomography (μCT) at the distal and mid-shaft of the femur and biochemical markers such as sclerostin and bone turnover markers at 1week and 3weeks of lactation and 2weeks post-weaning in osteocyte-specific sclerostin-overexpressed transgenic mice, and compared them with wild type. Lactation significantly resulted in decreased spine and femur BMD at day 7 and day 21 of breastfeeding; specifically, cortical microstructure (cross-sectional thickness and cross-sectional area) at the mid-shaft of the femur had significantly deteriorated. At day 14 after weaning, femur BMD and cortical microstructure at the mid-shaft of the femur in both the wild and DMP-SOST mice had incompletely recovered; however, spine BMD and trabecular microstructures at the distal femur recovered in wild type mice. Sclerostin, secreted by osteocytes, played a role in bone loss during lactation and also in the recovery of trabecular bone compartment by activating bone formation after weaning.