The myokine Irisin recapitulates the effect of physical activity on bone and muscle tissues

Osteoporosis, the skeletal disease characterized by decrease of bone mass and deterioration of its microarchitecture, and Sarcopenia, the muscle disease characterized by progressive loss of muscle mass and strength, are often concurrent diseases affecting the elderly population. These associated pathologies represent one of the major threats that increase the risk of fall-related fracture during the aging process. In addition to its severity, further exacerbated by loss of independence, hospitalization and subsequent depression faced by elderly people, this issue generate high healthcare expenses, which were estimated at approximately 32 billion euros per year in the 27 EU countries 1 and 22 billion dollars per year in the United States 2. Nevertheless, in light of the increased longevity of the population, the burden of concurrent osteoporosis and sarcopenia can further increase. Despite the high healthcare burden, there is no widely accepted clinical definition of sarcopenia, even though several diagnostic criteria have been suggested. However, a significant step forward has been made at least for converging the diagnostic approaches 3. The concomitant occurrence of osteoporosis and sarcopenia is very common during the process of aging and pathological conditions characterized by the disuse of the musculoskeletal system. However, to date there are no evidence about the mechanism responsible for the coupling of these two process. During the last decade, studies on the interactions between muscle and bone have made remarkable steps forward, establishing that skeletal muscle is an endocrine organ producing and releasing myokines acting in a paracrine or endocrine fashion. Among these, the newly identified myokine Irisin, produced by skeletal muscle after physical exercise, plays a key role in the bone-muscle functional unit, with a major impact on the skeleton by increasing cortical bone mineral density, modifying its geometry and improving bone strength. Furthermore, in vitro and in vivo studies reported an autocrine effect of Irisin on skeletal muscle and highlighted the autocrine myogenic potential of this myokine. This review summarizes new insights on the topic of Irisin action on bone and skeletal muscle, which support the hypothesis that Irisin may represent a novel molecular entity with exercise-mimetic properties. Hopefully future research may expand the knowledge of its ability to improve bone integrity and muscle activity and could pave the way for the use of Irisin as a new therapy for the prevention and treatment of musculoskeletal disorders, particularly useful for those patients that are not capable of performing physical activity, such as the elderly or bedridden patients.