Bone is a biomechanical tissue shaped by forces from muscles and gravitation. 
Simultaneous bone and muscle decay and dysfunction (osteosarcopenia or 
sarco-osteoporosis) is seen in ageing, numerous clinical situations including 
after stroke or paralysis, in neuromuscular dystrophies, glucocorticoid excess, 
or in association with vitamin D, growth hormone/insulin like growth factor or 
sex steroid deficiency, as well as in spaceflight. Physical exercise may be 
beneficial in these situations, but further work is still needed to translate 
acceptable and effective biomechanical interventions like vibration therapy from 
animal models to humans. Novel antiresorptive and anabolic therapies are 
emerging for osteoporosis as well as drugs for sarcopenia, cancer cachexia or 
muscle wasting disorders, including antibodies against myostatin or activin 
receptor type IIA and IIB (e.g. bimagrumab). Ideally, increasing muscle mass 
would increase muscle strength and restore bone loss from disuse. However, the 
classical view that muscle is unidirectionally dominant over bone via mechanical 
loading is overly simplistic. Indeed, recent studies indicate a role for 
neuronal regulation of not only muscle but also bone metabolism, bone signaling 
pathways like receptor activator of nuclear factor kappa-B ligand (RANKL) 
implicated in muscle biology, myokines affecting bone and possible 
bone-to-muscle communication. Moreover, pharmacological strategies inducing 
isolated myocyte hypertrophy may not translate into increased muscle power 
because tendons, connective tissue, neurons and energy metabolism need to adapt 
as well. We aim here to critically review key musculoskeletal molecular pathways 
involved in mechanoregulation and their effect on the bone-muscle unit as a 
whole, as well as preclinical and emerging clinical evidence regarding the 
effects of sarcopenia therapies on osteoporosis and vice versa.