Background: The pathophysiology of age-related bone loss and whether age-related bone loss can be prevented by exercise are still a matter of debate. Objective: It was the aim of this study to investigate the long-term effects of exercise and mild food restriction on bone mineral density (BMD) and bone geometry in the appendicular skeleton of aging male rats. Methods: Male Sprague-Dawley rats were studied from 5 to 23 months of age. The rats were divided into 4 groups: baseline, free access to food and running wheels (RW), fed to pair weight with the RW group (PW) and sedentary control animals with free access to food (SED). All rats were housed individually. Volumetric BMD and geometry of femurs and tibiae were assessed by peripheral quantitative computed tomography (pQCT). In addition, the tibial shafts were analyzed by cortical bone histomorphometry. Results: At the end of the experiment, RW and PW rats had similar body weight. The body weight of SED rats was 31% greater than that of RW rats. pQCT analysis of femurs and tibiae as well as histomorphometric analysis of the tibial shafts showed that dietary restriction resulted in an enlargement of the marrow cavity and cortical thinning at the femoral and tibial shafts relative to the RW and SED groups. Voluntary running exercise provided no additional protection against age-related bone loss when compared with the 31% heavier SED control rats. Neither exercise nor increased body weight in SED animals could completely prevent age-related bone loss between 19 and 23 months of age. Conclusion: We conclude that dietary restriction had clear negative effects on BMD and bone geometry and that running wheel exercise provided partial protection but could not prevent age-related bone loss.