DescriptionShort-term weight loss (WL) is accompanied by bone loss in postmenopausal women, but the longer-term impact is unclear. The goal of this study was to determine whether weight regain compared to maintenance of WL in reduced obese/overweight women has an impact on bone mineral density (BMD) and content (BMC). It was hypothesized that weight regain in reduced obese women would result in partial recovery of bone, as compared to women who maintain their lost weight. We measured hip, spine, forearm, and total body BMD and BMC by dual energy x-ray absorptiometry. Hormones, markers of bone turnover, and soft tissue were assessed. We recruited postmenopausal women (n=40, BMI of 28.2 +/- 2.9 kg/m2; 60.6 +/- 5.6 years) 1.5 years after a 6 month weight loss program who were categorized as regaining (>75%) or maintaining their weight lost. After 6 mo of WL, both groups lost -9.1 +/- 3.1% body weight with no significant difference between groups. At 23 +/- 6 mo after baseline, the weight-loss maintainers (WL-M, n=22) and weight-loss re-gainers (WL-R, n=18) lost -10.4 +/- 4.3 % and -2.6 +/- 3.6 % of their body weight. Participants averaged 1228 +/- 529 mg/d during the follow-up period, which did not differ significantly between the groups. The WL-M group showed greater BMD loss at the trochanter (p<0.05), 1/3 radius (p<0.05), and total body (p<0.02) compared with the WL-R group. WL-M also showed a trend to decrease serum osteocalcin (p<0.08) and increase cortisol (p<0.09) more than the WL-R group, as measured in a subset of women (WL-M n=10, WL-R n=8). There were positive relationships between the change in fat mass and 1/3 radius (r=0.047, p<0.01) and total body (r=0.519, p<0.001) in the entire group of women (n=40) while changes at the trochanter and 1/3 radius correlated with leg fat (r>0.422, p<0.01), but not trunk fat, suggesting that regional fat tissue may have a differential influence on bone. These data in postmenopausal women show that bone continues to decline at the trochanter and femoral neck over a 2 year period with 10% weight loss, and with weight regain there is partial recovery of bone.