Fig. 1From: The bone–muscle connection in breast cancer: implications and therapeutic strategies to preserve musculoskeletal healthStates of high bone turnover release TGF-β into systemic circulation. In skeletal muscle, bone-derived TGF-β results in upregulation of NADPH oxidase 4 (Nox4), producing reactive oxygen species that destabilize RyR1-calstabin1 complex. This leads to calcium leak and muscle weakness, further unloading and weakening bone strength in a feed-forward cycle of musculoskeletal decline (figure adapted and modified from Waning and Guise et al., Nature Med, 2015)Back to article page