Sex specific effects of irisin on the skeleton

Irisin, the circulating protein derived from cleavage of fibronectin type III domain containing protein 5 (FNDC5) has attracted considerable attention regarding its positive effects on a number of organs/tissues such as fat, brain, and heart. However, effects on bone can appear to be either positive or negative depending on context and sex. Sex differences have also been described in Alzheimer’s disease also emphasizing sex differences in response to irisin. Here in this review, we outline and focus on the effects of irisin on osteoblasts, osteoclasts, and osteocytes, murine models, and human studies. The consideration of sex effects is necessary especially in the context of irisin serving as a therapeutic.