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Review
. 2022 Nov 21;11(22):6863.
doi: 10.3390/jcm11226863.

Irisin and Bone in Sickness and in Health: A Narrative Review of the Literature

Elena Tsourdi  1   2 , Athanasios D Anastasilakis  3 , Lorenz C Hofbauer  1   2 , Martina Rauner  1   2 , Franziska Lademann  1   2
Affiliations
Review

Irisin and Bone in Sickness and in Health: A Narrative Review of the Literature

Elena Tsourdi et al. J Clin Med. .

Abstract

Irisin is a hormone-like myokine produced by the skeletal muscle in response to exercise. Upon its release into the circulation, it is involved in the browning process and thermogenesis, but recent evidence indicates that this myokine could also regulate the functions of osteoblasts, osteoclasts, and osteocytes. Most human studies have reported that serum irisin levels decrease with age and in conditions involving bone diseases, including both primary and secondary osteoporosis. However, it should be emphasized that recent findings have called into question the importance of circulating irisin, as well as the validity and reproducibility of current methods of irisin measurement. In this review, we summarize data pertaining to the role of irisin in the bone homeostasis of healthy children and adults, as well as in the context of primary and secondary osteoporosis. Additional research is required to address methodological issues, and functional studies are required to clarify whether muscle and bone damage per se affect circulating levels of irisin or whether the modulation of this myokine is caused by the inherent mechanisms of underlying diseases, such as genetic or inflammatory causes. These investigations would shed further light on the effects of irisin on bone homeostasis and bone disease.

Keywords: FNDC5; bone mineral density; fractures; irisin; osteoporosis; sarcopenia.

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Conflict of interest statement

E. Tsourdi received honoraria for lectures and advisory boards from Amgen, UCB, Takeda, Kyowa Kirin, and educational grants from Takeda and UCB. A.D. Anastasilakis reports lecture fees from Amgen, Bianex, Eli-Lilly, ITF, and UCB. M. Rauner received honoraria for lectures from Amgen, UCB, Diasorin and research materials from Novartis, Acceleron, and Regeneron. L.C. Hofbauer reports honoraria for advisory boards from Alexion, Amgen, Merck, Radius, Roche, Shire, and UCB to his institution and himself. F. Lademann has nothing to disclose.

Figures

Figure 1
Figure 1
Irisin and bone in humans. Exercise increases the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), a transcriptional regulator of fibronectin type III domain-containing protein 5 (FNDC5), in muscle tissue, as well as circulating levels of the myokine irisin. An upregulation of FNDC5 has not yet been confirmed in the muscle tissue of humans, but only in rodent models, and the exact cleavage mechanisms of FNDC5 into irisin, as well as the local concentrations or secretion of irisin in bone tissues, need further exploration. High serum irisin levels positively correlate with bone mass, bone mineral density, and bone turnover in healthy children and adults, while they are negatively associated with osteoporotic fracture risk. Created with Biorender.com (accessed on 2 March 2022).
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