Fig 8: Graphical abstract (image was created using BioRender.com).

No differences are observed in bone from Fndc5 /irisin null female, whereas null male skeletons are larger but weaker compared to wildtype controls.

With calcium deficiency, lactating female null mice are protected from bone loss due to osteocytic osteolysis, whereas male null mice on a low calcium diet lose greater amounts of bone compared to their wildtype controls.

The osteocyte transcriptomes show wildtype males have higher expression of the steroid, lipid and fatty acid pathways which are lower in the null males, whereas the wildtype females have higher expression of genes regulating osteocytic osteolysis than null females.

With calcium deficiency, female null osteocytes have lower while male null osteocytes have higher expression of osteocytic osteolysis genes compared to wildtype controls.