Abstract Dietary restriction (DR) increases the life span and retards the development of age-related disorders. However, the low body mass that accompanies DR is associated with risk factors for fracture that may outweigh the beneficial effects of DR on cellular aging that are mediated, in part, by limiting free radical generation and oxidative damage. We tested the effects of DR in murine models that differ in free radical generation capacity (SENCAR > C57 > DBA). Male mice of each strain were killed at 10 weeks of age (t 0; time zero) or randomized to an ad libitum-fed (AL-fed) or 30% DR feeding regimen for 6 months. The food consumption of AL-fed mice was measured daily. DR mice received 70% of the amount of food consumed by their respective AL-fed mice the previous day. The DR diet was normalized with respect to calcium (Ca), phosphorus (P), and micronutrients. Lean body mass (LBM), bone mineral density (BMD), and bone mineral content (BMC) in the humerus and mandible were determined by PIXImus densitometry. The length and midshaft width of the humerus were determined by direct measurement. There were highly strain- and diet/time-dependent effects on LBM, humerus length, mandibular and humeral BMD, and humeral BMC. The interaction between diet/time and strain was more significant in the humerus than the mandible. All 30% DR mice had lower humeral BMDs and BMCs than their respective AL-fed controls. However, 30% DR C57 and DBA (but not SENCAR) mice had higher humeral BMD and BMC than their respective t 0 controls. There was a linear relationship between LBM and humeral BMD and BMC in both AL-fed and 30% DR mice, suggesting that the lower BMD and BMC in 30% DR mice, relative to AL-fed controls, reflects a physiologic adaptation to lower biomechanical loading. Mandibular BMC in 30% DR C57 (but not DBA or SENCAR) mice was lower than that observed in their AL-fed controls. Mandibular BMD and BMC increased versus t 0 values in 30% DR mice of all strains.