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Background: Bone loss often accompanies weight loss induced by caloric restriction (CR), but whether bone loss accompanies similar weight loss induced by exer-cise (EX) is unknown. We tested the hypothesis that EX-induced weight loss is associated with less bone loss com-pared with CR-induced weight loss. Methods: Forty-eight adults (30 women; 18 men; mean±SD age, 57±3 years; and mean±SD body mass in-dex, 27±2 kg/m2) were randomized to 1 of 3 groups for 1 year: CR group (n=19), regular EX group (n=19), or a healthy lifestyle (HL) control group (n=10). Primary outcome measure was change in hip and spine bone min-eral density (BMD). Secondary outcomes were bone mark-ers and hormones. Results: Body weight decreased similarly in the CR and EX groups (10.7%±6.3 % [−8.2±4.8 kg] vs 8.4%±6.3% [−6.7±5.6 kg]; P=.21), whereas weight did not change in the HL group (−1.2%±2.5 % [−0.9±2.0 kg]). Com-pared with the HL group, the CR group had decreases in BMD at the total hip (−2.2%±3.1 % vs 1.2%±2.1%; P=.02) and intertrochanter (−2.1%±3.4 % vs 1.7±2.8%; P=.03). The CR group had a decrease in spine BMD (−2.2%±3.3%;P=.009). Despite weight loss, the EX group did not demonstrate a decrease in BMD at any site. Body weight changes correlated with BMD changes in the CR (R=0.61; P=.007) but not in the EX group. Bone turn-over increased in both CR and EX groups. Conclusions: CR-induced weight loss, but not EX-induced weight loss, is associated with reductions in BMD at clinically important sites of fracture. These data sug-gest that EX should be an important component of a weight loss program to offset adverse effects of CR on bone