Targeting the Muscle-Bone Unit: Filling Two Needs with One Deed in the Treatment of Duchenne Muscular Dystrophy

Purpose of Review In Duchenne muscular dystrophy (DMD), the progressive skeletal and cardiac muscle dysfunction and degeneration is accompanied by low bone mineral density and bone fragility. Glucocorticoids, which remain the standard of care for patients with DMD, increase the risk of developing osteoporosis. The scope of this review emphasizes the mutual cohesion and common signaling pathways between bone and skeletal muscle in DMD. Recent Findings The muscle-bone interactions involve bone-derived osteokines, muscle-derived myokines, and dual-origin cytokines that trigger common signaling pathways leading to fibrosis, inflammation, or protein synthesis/degradation. In particular, the triad RANK/RANKL/OPG including receptor activator of NF-kB (RANK), its ligand (RANKL), along with osteoprotegerin (OPG), regulates bone matrix modeling and remodeling pathways and contributes to muscle pathophysiology in DMD. Summary This review discusses the importance of the muscle-bone unit in DMD and covers recent research aimed at determining the muscle-bone interactions that may eventually lead to the development of multifunctional and effective drugs for treating muscle and bone disorders regardless of the underlying genetic mutations in DMD.