Lactation places large metabolic demands on a mother’s skeleton. To mobilize the minerals needed for milk production, osteocytes—the cells responsible for maintaining bone quality—facilitate the release of calcium and other minerals from the bone. In this study, researchers investigated how this process occurs throughout the bone during lactation and how osteocytes balance the rapid release of calcium while maintaining bone integrity.
“We know that lactation leads to significant changes in bone, but understanding how these changes occur at both the osteocyte cellular and bone structural levels was crucial,” said Claire Acevedo, an assistant professor at the University of California San Diego. Researchers from UC San Diego and UC San Francisco compared virgin and lactating mice, with and without the osteocyte-specific deletion of an enzyme (MMP13) responsible for the resorption of bone matrix surrounding the osteocytes. To visualize and quantify local changes in mouse tibias, they employed microcomputed tomography at Advanced Light Source (ALS) Beamline 8.3.2.
The team discovered that lactation-induced bone remodeling is highly spatially controlled. Osteocytes located near the bone’s vascular structures experienced significant local bone matrix resorption and calcium release, leading to a substantial increase in the volume of lacunae (i.e., cavities where osteocytes reside). In contrast, osteocytes near the bone’s outer surface showed little activity. The findings suggest that osteocytes located near vasculature, facilitating calcium transport, play a more active role in calcium mobilization during lactation.
Additionally, the researchers discovered that lactation led to the formation of hypomineralized regions 14–20 µm away from the osteocyte lacunae, particularly in larger lacunae undergoing active resorption. These hypomineralized regions, indicative of calcium removal, demonstrate that osteocytes can resorb minerals not only around the lacunae via MMP13 but also further away, at the tips of their branches (called “dendritic processes”), independent of peri-lacunar resorption and MMP13.
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Image: Representative 3D renderings of the lacunae and vasculature in mouse bones, generated using synchrotron microcomputed tomography. Vasculature is colored white, and lacunae are colored according to volume.