Bone tissue is a dynamic organ which undergoes constant remodeling through a coupled series of events in order to maintain proper skeletal structure and calcium-phosphate homeostasis. In addition to its mechanical properties, extensive research has revealed bone to modulate multiple metabolic processes as well, and it is wide-ly accepted that bone tissue engages in active crosstalk with different tissue types. 

Activins are pleiotropic growth factors belonging to the transforming growth factor β-superfamily and have recently been associated with numerous pathologic states affecting the musculoskeletal system. As activins are highly expressed in bone, the clarification of the true roles of activins in the pathogenesis of skeletal disorders could lead to the development of novel therapeutics targeting these growth factors. To address this, we investigated the effect of soluble activin type IIB receptor (ActRIIB-Fc), an activin-signaling inhibitor, on bone formation and body composi-tion in different animal models. 

In this series of translational studies we show that treatment with ActRIIB-Fc im-proves bone mass and strength as well as induces an increase in muscle mass in a mouse model of Duchenne muscular dystrophy. We also demonstrate that ActRIIB-Fc enhances fracture healing in a closed, diaphyseal fracture mouse mod-el. Finally, we showed that treatment with ActRIIB-Fc rescues bone loss and fat gain induced by estrogen deficiency in an ovariectomy-mouse model. Our novel results propose that ActRIIB-Fc affects multiple tissue types in clinically relevant models and could be a potential therapeutic approach in different musculoskeletal and metabolic disorders, in which bone, fat and muscle are affected.