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Skeletal loading in vertebrates controls modeling drifts, modulated remodeling rates, and affects growth trajectories. It is unclear whether the majority of the mechanical stimulus detected by bone cells originates from muscle contraction forces or from gravitational forces associated with substrate impact. Several clinical and basic science reports indicate that muscle forces play a dominant role in generating the mechanical stimulus in exercise-induced bone gain. Although it is, in most cases, difficult to separate the effects of gravitational forces acting on body mass from muscle contractions, several well-conceived experiments offer considerable insight into the propensity of muscle-derived forces per se to drive the adaptive response in bone. Load-induced osteogenesis requires that mechanical signals come packaged with particular characteristics, all of which can be generated from either gravitational or muscle forces. Neither of these two sources have been demonstrated empirically to be the source of bone's adaptive response, but a convincing body of data suggests that muscle contractions are present, significant, and capable of accounting for most of the adaptive responses.