OBJECTIVE Excessive pressure due to wearing mal-adapting dentures is well known to cause residual bone resorption beneath the denture. X-rays have been commonly utilized to evaluate the changes in the bone beneath the denture. However, X-ray images merely detect bone density and relatively large changes in the bone shape and structure, whereas nuclear medicine imaging can detect functional changes, which occur prior to structural changes. This article aimed to describe the time course of the bone metabolism at the residual ridge beneath the denture following denture use by (18)F-fluoride positron emission computerized-tomography (PET)/computed tomography (CT) scanning. METHODS Three subjects, who had a free-end edentulous mandible, were treated with a denture replacing the edentulous region of the dental arch. The metabolic changes in the residual bone beneath the denture were assessed by (18)F-fluoride PET/CT imaging. (18)F-fluoride PET/CT scanning was performed at baseline, and 4-6 and 13 weeks after denture use. A volume of interest (VOI) was placed on their mandibles at the edentulous region beneath the denture on the PET/CT image. CT value and mean standardized uptake value (SUV) of the VOI were calculated. The difference in the time variation between the CT value and SUV was analyzed. RESULTS The adaptation of the denture base to the residual ridge was successful, and there was no trouble such as pain at the residual ridge beneath the denture. The SUVs of each VOI significantly increased at 4-6 weeks after denture use and then decreased at 13 weeks in all three subjects (P < 0.05; two-way ANOVA, Dunnett test). On the other hand, the CT images showed no obvious changes in the bone shape or structure beneath the dentures, and the CT values of each VOI remained static after denture use in all three subjects. CONCLUSIONS This study indicates that in the present first-time removable partial denture (RPD) users, wearing of a well-adapted RPD initially increased bone metabolism beneath the denture and then decreased it at around 13 weeks after RPD use without any bone structural changes detectable by clinical X-rays. These metabolic changes are a mechanobiological reaction to the pressure induced by RPD use.