Anti-RANKL Therapy Prevents Glucocorticoid-Induced Bone Loss and Promotes Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy


Bisphosphonates are recommended to prevent bone loss in glucocorticoid-treated boys with Duchenne muscular dystrophy (DMD). This study explores the potential benefits of targeting receptor activator of nuclear factor kappa-B ligand (RANKL) in DMD, due to its impact on both bone and dystrophic skeletal muscle function. In an 8-week experiment with mdx mice, anti-RANKL and deflazacort (DFZ) individually improves grip force performance and bone microstructure, with anti-RANKL also enhancing ex-vivo contractile properties of dystrophic muscles. A subsequent study reveals that intravenous zoledronate administration is necessary to sustain bone improvements in mice after discontinuation of anti-RANKL treatment, highlighting the potential of anti-RANKL therapy in restoring muscle function without steroid-related skeletal side effects in DMD.