Weight reduction induces bone loss by several factors, and the effect of higher protein (HP) intake during caloric restriction on bone mineral density (BMD) is not known. Previous study designs examining the longer-term effects of HP diets have not controlled for total calcium intake between groups and have not examined the relationship between bone and endocrine changes. In this randomized, controlled study, we examined how BMD (areal and volumetric), turnover markers, and hormones [insulin-like growth factor 1 (IGF-1), IGF-binding protein 3 (IGFBP-3), 25-hydroxyvitamin D, parathyroid hormone (PTH), and estradiol] respond to caloric restriction during a 1-year trial using two levels of protein intake. Forty-seven postmenopausal women (58.0 AE 4.4 years; body mass index of 32.1 AE 4.6 kg/ m 2 ) completed the 1-year weight-loss trial and were on a higher (HP, 24%, n ¼ 26) or normal protein (NP, 18%, n ¼ 21) and fat intake (28%) with controlled calcium intake of 1.2 g/d. After 1 year, subjects lost 7.0% AE 4.5% of body weight, and protein intake was 86 and 60 g/d in the HP and NP groups, respectively. HP compared with NP diet attenuated loss of BMD at the ultradistal radius, lumbar spine, and total hip and trabecular volumetric BMD and bone mineral content of the tibia. This is consistent with the higher final values of IGF-1 and IGFBP-3 and lower bone-resorption marker (deoxypyridinoline) in the HP group than in the NP group ( p < .05). These data show that a higher dietary protein during weight reduction increases serum IGF-1 and attenuates total and trabecular bone loss at certain sites in postmenopausal women. ß

High protein intake is a popular method to achieve weight (wt) reduction; however its effect on bone remains controversial. Understanding whether dietary protein intake influences bone mass during caloric restriction was the goal in this study while controlling for dietary calcium. We examined 40 postmenopausal women (58 ¡À 5 years; BMI of 32.4 ¡À 5.7 kg/m2), who were assigned to caloric restriction and 1.2 g Ca/day with either a normal (NP, 18%, n =20) or higher (HP, 30%, n =20) protein intake and a low fat intake (28%). Bone measurements using dual energy x‐ray absorptiometry were performed at baseline, and 6 and 12 months after wt loss. Here we report the data after 6 months of wt loss (‐7.3 ¡À 4%) that did not differ significantly between groups. Total body bone mineral density and lumbar spine bone mineral content decreased (p<0.05) more in the NP (‐2.0% and ‐1.6% respectively) compared to HP group (‐0.1 % and 1.2% respectively). In a subset of women (n=22), bone turnover markers were measured and showed no changes, but there was a trend (p¡Ü0.08) for a greater increase in serum 25‐hydroxyvitamin D and parathyroid hormone in the NP than HP group, that requires confirmation in the entire group. These data suggest that higher dietary protein attenuates bone loss during wt reduction in postmenopausal women. Further analysis of the mechanisms mediating these changes is being addressed.SUPPORT: NIḦCAG12161, Busch Biomedical GrantGrant Funding SourceNIA‐NIH