By micro-Ct analysis, we demonstrated that irisin improves MM-induced trabecular bone damage by partially preventing the reduction of femur Trabecular Bone Volume/Total Volume (<i>P</i> = .0028), Trabecular Number (<i>P</i> = .0076), Trabecular Fractal Dimension (<i>P</i> = .0044), and increasing Trabecular Separation (<i>P</i> = .0003) in MM mice. Here, FNDC5 is linked to Miyoshi myopathy.