The skeleton's ability to sustain loads without fracture requires bone mass and architecture to be appropriate for the loading involved. Load-bearing is the only functional influence which requires any particular bone architecture, and functionally-engendered strains provide the only feedback relevant to both the bone's loading and its structural suitability. The specific strain-related objectives of the mechanically-related modelling/remodelling response responsible for matching structure to load-bearing have not been adequately defined but they appear to be different for cortical and cancellous bone. Static loads have no effect on modelling/remodelling activity whereas the effects of dynamic loading can be profound. The osteogenic effect of loading appears to be greatest when the strains and strain rates are high and the strain distributions unusual. This raises the possibility of continued load-bearing which only involves restricted activity patterns being interpreted by the bones' cell population as relative disuse. The osteogenic stimulus of each loading configuration appears to saturate after a few daily loading cycles. Since loading produces a local effect on modelling/remodelling, exercise regimens whose objective is to preserve or increase bone mass must be designed in relation to load-bearing at each skeletal location. Through their independent effects on bone cells nutritional and hormonal factors can enable, enhance, limit, or frustrate full expression of the adaptive response to loading. However, such systemic factors cannot engender, or successfully imitate, the cumulative local osteo-regulatory effects which loading engenders. This explains the absence of any natural systemic substances capable of engendering a sustained, structurally appropriate increase in bone mass. Preventing the incidence of fracture by load-bearing regimens designed to increase or maintain bone mass before crush fractures occur is obviously preferable to attempting such treatment in a skeleton which is already demonstrably inadequate. Since systemic influences and the effects of local load-bearing clearly interact there is potential for intervention to maintain or increase bone mass by combined therapy. Therapeutic imitation or manipulation of the mechanically-adaptive response awaits satisfactory definition of the cellular mechanism(s) normally involved in mechanically-related control of bone architecture.