Bone adaptation is understood to be driven by mechanical strains acting on the bone as a result of some mechanical stimuli. Although the strain/adaptation relation has been extensively researched using in vivo animal loading models, it has not been studied in humans, likely due to difficulties in quantifying bone strains and adaptation in living humans. Our purpose was to examine the relationship between bone strain and changes in bone mineral parameters at the local level. Serial computed tomography (CT) scans were used to calculate 14 week changes in bone mineral parameters at the distal radius for 23 women participating in a cyclic in vivo loading protocol (leaning onto the palm of the hand), and 12 women acting as controls. Strains were calculated at the distal radius during the task using validated finite element (FE) modeling techniques. Twelve subregions of interest were selected and analyzed to test the strain/adaptation relation at the local level. A positive relationship between mean energy equivalent strain and percent change in bone mineral density (BMD) (slope = 0.96%/1000 με, p < 0.05) was observed within experimental, but not control subjects. When subregion strains were grouped by quartile, significant slopes for quartile versus bone mineral content (BMC) (0.24%/quartile) and BMD (0.28%/quartile) were observed. Increases in BMC and BMD were greatest in the highest-strain quartile (energy equivalent strain > 539 με). The data demonstrate preliminary prospective evidence of a local strain/adaptation relationship within human bone. These methods are a first step toward facilitating the development of personalized exercise prescriptions for maintaining and improving bone health.