Of the U.S. population, 65% is either overweight or obese, and weight loss is recommended to reduce co-morbid conditions. However, bone mobilization and loss may also occur with weight loss. The risk for bone loss depends on initial body weight, age, gender, physical activity, and conditions of dieting such as the extent of energy restriction and specific levels of nutrient intake. Older populations are more prone to bone loss with weight loss; in women, this is due at least in part to a reduced dietary Ca intake and/or efficiency of absorption. Potential hormonal mechanisms regulating bone loss during weight loss are discussed, including decreases in estrogen, leptin, glucagon-like peptide-2, growth hormone, and insulin-like growth factor-1, or an increase in cortisol. In contrast, the rise in adiponectin and ghrelin with weight reduction should not be detrimental to bone. Combining energy restriction with exercise does not necessarily prevent bone loss, but may attenuate loss as was shown with additional Ca intake or osteoporosis medications. Future controlled weight loss trials should be designed to further address mechanisms influencing the density and quality of bone sites vulnerable to fracture, in the prevention of osteoporosis.

High bone turnover conditions result in Pb mobilization from bone into circulation. In Pb-exposed rodents, weight loss has been shown to increase blood Pb levels. It remains unknown whether weight loss in humans increases blood Pb levels due to mobilization of inert Pb stores. We measured whole blood Pb levels (206Pb, 207Pb, 208Pb) by inductively-coupled plasma mass spectrometry in 74 women (age 24–75 years; BMI 23–74) before and 6 months after moderate (n=39) or severe (n=17) weight loss (WL), or weight maintenance (WM, n=18). Before wt loss, baseline blood Pb ranged from 0.02–6.0 μg/dL, (optimum levels < 10 ug/dL), and showed a positive association with age (r = 0.50 for 206–208Pb, p < 0.0001). Since all three Pb isotopes responded to treatment in a similar manner, 206Pb is reported for the rest of the results. After severe WL (−35.9 ± 15.2 kg), blood Pb levels increased (p < 0.05, Figure) to 3.8 ± 3.1 ug/dL (1.3–12.5 μg/dL). Moderate WL (−5.6 ± 2.7 kg) and WM (0.4 ± 1.3 kg) did not result in an increase in Pb levels (Figure). Blood Pb levels increased more with greater weight loss (r = 0.23, p < 0.05), but there was no significantcorrelation between blood Pb and a rise in bone turnover markers. Overall, we show that severe, but not moderate weight loss increases levels of blood Pb, and suggest that this could cause Pb toxicity in people with previous excessive lead exposure, especially in an older population (NIH-NIEHS). Figure 1Open in figure viewerPowerPoint

Overweight postmenopausal women may be more susceptible to bone loss with weight reduction than previously studied obese women. The influence of energy restriction and Ca intake on BMD was assessed in 66 individuals. Weight reduction resulted in bone loss at several sites in women consuming 1 g Ca/day and was mitigated with higher calcium intake at 1.7 g/day.Introduction: Bone loss is associated with weight loss in obese postmenopausal women and can be prevented with calcium (Ca) supplementation. However, because bone loss caused by weight loss may be greater in overweight than obese women, it is not clear whether Ca supplementation is also beneficial in overweight women.Materials and Methods: We assessed the influence of caloric restriction at two levels of Ca intake on BMD and BMC in 66 overweight postmenopausal women (age, 61 +/- 6 years; body mass index, 27.0 +/- 1.8 kg/m(2)). Subjects completed either a 6-month energy-restricted diet (WL, n = 47) and lost 9.3 +/- 3.9 % weight or maintained weight (WM; 1 g Ca/day, n = 19). Participants in the WL group were randomly assigned to either normal (1 g/day; WL NL-Ca) or high (1.7 g/day; WL HI-Ca) Ca intake. Regional BMD and BMC were measured at baseline and after 6 months.Results: During normal Ca intake, trochanter BMD and BMC and total spine BMD were decreased more in WL than WM women (p < 0.05). The WL NL-Ca group lost more trochanter BMD (-4.2 +/- 4.1 %) and BMC (-4.8 +/- 7.1 %) than the WL Hi-Ca group (-1.4 +/- 5.6% and -1.1 +/- 8.1%, respectively; p < 0.05). There were no significant changes in BMD or BMC at the femoral neck in any group. Weight loss correlated with trochanter BMD loss (r = 0.687, p < 0.001) in the WL NL-Ca group.Conclusion: Despite an intake of I g Ca/day, bone loss occurred at some sites because of weight loss. Calcium intake of 1.7 g/day will minimize bone loss during weight loss in postmenopausal overweight women.

Data suggest that a diet deficient in calcium is associated with higher body weight and that augmenting calcium intake may reduce weight and fat gain or enhance loss. Our aim was to determine whether calcium supplementation during a weight loss intervention affects body fat or weight loss. Data were combined from three separate 25-wk randomized, double blind, placebo-controlled trials of 1000 mg/d calcium supplementation in 100 premenopausal and postmenopausal women. The primary outcome measures were change in body weight and fat mass adjusted for baseline values. There were no significant differences in body weight or fat mass change between the placebo and the calcium-supplemented groups in the pooled analysis (adjusted mean +/- SE; body weight, placebo -6.2 +/- 0.7 vs. Ca -7.0 +/- 0.7 kg; fat mass, placebo -4.5 +/- 0.6 vs. Ca -5.5 +/- 0.6 kg), and no significant interactions of calcium supplementation with menopausal/diet status. Analysis as separate trials also found no significant differences between the placebo and the calcium groups. Calcium supplementation did not significantly affect amount of weight or fat lost by women counseled to follow a moderately restricted diet for 25 wk. Nevertheless, the magnitude and direction of the differences for group means are consistent with a hypothesized small effect.

Weight reduction is a risk factor for bone loss. We previously showed that energy restriction is associated with a decrease in calcium (Ca) absorption and decreased estrogenic activity (EA). We hypothesized that this hypoestrogenic status may be the cause of the decrease in Ca absorption and that estrogen replacement during energy restriction would prevent it. Six-month-old rats were ovariectomized and implanted subcutaneously with 17beta-estradiol (E(2)) pellets to maintain levels within the physiological range. After 3 wk, rats ate ad libitum [control (CTL) group, n = 12] or were 40% energy restricted (EnR group, n = 12) for 10 wk. At the end of this study, rats were divided into 2 groups according to their uterine weight: those with higher EA and those with lower EA. Whereas CTL rats gained approximately 46% weight from baseline, EnR rats maintained their weight throughout the study. Energy restriction was associated with lower Ca absorption (5-d measurement, (45)Ca radioisotope) and Ca balance in lower EA but not higher EA rats. Similarly, Ca absorption was correlated with both serum E(2) (r = 0.68, P < 0.05) and body weight (r = 0.72, P < 0.05) in rats with lower EA but not in those with higher EA. Finally, 24-h corticosterone excretion was higher in EnR than in CTL rats, a response that was blunted in the higher EA rats. Our findings suggest that decreases in estrogen and hyperadrenocorticism with energy restriction play an important role in the regulation of Ca absorption and balance.

BACKGROUNDWeight loss (WL) reduces bone mass and increases fracture risk. Mechanisms regulating calcium metabolism during WL are unclear.OBJECTIVEThe objective was to assess the effect of 6 wk of WL at 2 different amounts of calcium intake [normal (NlCa): 1 g/d; high (HiCa): 1.8 g/d] on true fractional calcium absorption (TFCA), bone turnover, and bone-regulating hormones in overweight postmenopausal women.DESIGNSeventy-three women (body mass index, 26.9 +/- 1.9 kg/m(2)) were recruited either to consume a moderately energy-restricted diet (WL group) or to maintain their body weight [weight-maintenance (WM) group] and were randomly assigned to either the HiCa or the NlCa group in a double-blind manner. Subjects underwent weekly diet counseling, and measurements were taken at baseline and after 6 wk.RESULTSFifty-seven women completed the study and had a baseline TFCA of 24.9 +/- 7.4%. Energy restriction significantly decreased the total calcium absorbed (P < 0.05) in the WL group (n = 32) compared with the WM group (n = 25; analysis of covariance). Regression analysis showed that a greater rate of weight loss suppressed TFCA and the total calcium absorbed (P < 0.05) in the HiCa group. The women in the NlCa WL group absorbed inadequate amounts of calcium (195 +/- 49 mg/d), whereas the women in the HiCa WL group absorbed adequate amounts (348 +/- 118 mg/d). Parathyroid hormone explained 22% of the variance in calcium absorbed in the NlCa group only.CONCLUSIONSWe suggest that WL is associated with elevated calcium requirements that, if not met, could activate the calcium-parathyroid hormone axis to absorb more calcium. Normal intakes of calcium during energy restriction result in inadequate total calcium absorption and could ultimately compromise calcium balance and bone mass.

Objective: To examine bone mass and metabolism in women who had previously undergone Roux-en-Y gastric bypass (RYGB) and determine the effect of supplementation with calcium (Ca) and vitamin D.Research Methods and Procedures: Bone mineral density and bone mineral content (BMQ were examined in 44 RYGB women ( greater than or equal to3 years post-surgery; 31% weight loss; BMI, 34 kg/m(2)) and compared with age- and weight-matched control (CNT) women (n = 65). In a separate analysis, RYGB women who presented with low bone mass (n = 13) were supplemented to a total 1.2 g Ca/d and 8 mug vitamin D/d over 6 months and compared with an unsupplemented CNT group (n = 13). Bone mass and turnover and serum parathyroid hormone (PTH) and 25-hydroxyvitamin D were measured.Results: Bone mass did not differ between premenopausal RYGB and CNT women (42 +/- 5 years), whereas postmenopausal RYGB women (55 +/- 7 years) had higher bone mineral density and BMC at the lumbar spine and lower BMC at the femoral neck. Before and after dietary supplementation, bone mass was similar, and serum PTH and markers of bone resorption were higher (p < 0.001) in RYGB compared with CNT women and did not change significantly after supplementation.Discussion: Postmenopausal RYGB women show evidence of secondary hyperparathyroidism, elevated bone resorption, and patterns of bone loss (reduced femoral neck and higher lumbar spine) similar to other subjects with hyper-parathyroidism. Although a modest increase in Ca or vitamin D does not suppress PTH or bone resorption, it is possible that greater dietary supplementation may be beneficial.

Weight loss is associated with bone loss and the risk may be greater in lean than heavier individuals, but the mechanisms involved remain unclear. We hypothesized that energy restriction (EnR) would decrease true fractional Ca absorption (TFCA) and be mediated by Ca-regulating hormones, but differently in obese and lean rats. Rats were fed a high fat (47% energy) or low fat (16% energy) diet for 4 mo. At 6 mo of age, the resulting lean [284 +/- 28g (mean +/- SD, n = 18)] and obese (319 +/- 34g, n = 20) groups (P < 0.005) were divided into controls (CTL, ad libitum) and energy-restricted (40% restriction) groups. At baseline, bone resorption (urinary crosslinks) was higher and bone formation (serum osteocalcin) was lower in obese than in lean rats, whereas Ca balance components and Ca-regulating hormones did not differ. EnR for 10 wk reduced body weight by 25 +/- 7% compared with a 6 +/- 6% gain in CTL rats (P < 0.001). For both lean and obese rats, TFCA (5-d measurement, (45)Ca radioisotope) decreased from 30 +/- 9% to 24 +/- 9% with EnR, compared with 25 +/- 10% to 29 +/- 11% in controls (P < 0.05). Weight loss was directly correlated with the decrease in TFCA (r = 0.34, P < 0.05). Uterine weights indicated a reduced estrogenic activity in energy-restricted rats (P < 0.0001). In lean, but not obese rats, serum estradiol (E(2)) correlated with weight loss (r = 0.52, P < 0.05), and tended to correlate with the decrease in TFCA (r = 0.48, P = 0.06). At the end of the study, serum 25-hydroxyvitamin-D was lower and urinary Ca was higher in lean than obese energy-restricted rats. Distinct endocrine profiles during weight loss in obese and lean rats suggest that the susceptibility of bone and Ca metabolism to EnR could differ depending on initial body weight.

Energy restriction (ER) extends the life span and slows aging and age-related diseases in short-lived mammalian species. Although a wide variety of physiological systems have been studied using this paradigm, little is known regarding the effects of ER on skeletal health and reproductive aging. Studies in rhesus monkeys have reported that ER delays sexual and skeletal maturation in young male monkeys and reduces bone mass in adult males. No studies have examined the chronic effects on bone health and reproductive aging in female rhesus monkeys. The present cross-sectional study examined the effects of chronic (6 y) ER on skeletal and reproductive indices in 40 premenopausal and perimenopausal (7-27 y old) female rhesus macaques (Macaca mulatta). Although ER monkeys weighed less and had lower fat mass, ER did not alter bone mineral density, bone mineral content, osteocalcin, 25-hydroxyvitamin D, 1,25-hydroxyvitamin D or parathyroid hormone concentrations, menstrual cycling or reproductive hormone concentrations. Body weight and lean mass were significantly related to bone mineral density and bone mineral content at all skeletal sites (total body, lumbar spine, mid and distal radius; P: < or = 0.04). The number of total menstrual cycles over 2 y, as well as the percentage of normal-length cycles (24-31 d), was lower in older than in younger monkeys (P: < or = 0.05). Older monkeys also had lower estradiol (P: = 0.02) and higher follicle-stimulating hormone (P: = 0.02) concentrations than did younger monkeys. We conclude that ER does not negatively affect these indices of skeletal or reproductive health and does not alter age-associated changes in the same variables.

Bone turnover is increased during weight loss in postmenopausal women and can be suppressed with calcium supplementation. In this study, we assessed the influence of energy restriction with and without calcium supplementation (1 g/day) in premenopausal women. Thirty‐eight obese premenopausal women (body mass index [BMI] of 35.0 ± 3.9 kg/m2) completed a 6‐month study of either moderate weight loss or weight maintenance. During weight loss, women were randomly assigned to either a calcium supplementation (n = 14) or placebo group (n = 14) and lost 7.5 ± 2.5% of their body weight. The control group of women (n = 10) maintained their body weight. Total body and lumbar bone mineral density (LBMD) and content were measured by dual‐energy X‐ray absorptiometry (DXA) at baseline and after weight loss. Throughout the study, blood and urine samples were collected to measure bone turnover markers and hormones. During moderate energy restriction, dietary calcium intake decreased (p < 0.05) and the bone resorption marker deoxypyridinoline (DPD) increased slightly (p ≤ 0.05) without evidence of bone loss. Calcium supplementation during weight loss tended to increase lumbar BMD by 1.7% (p = 0.05) compared with the placebo or weight maintenance groups. In contrast to our previous findings in postmenopausal women, premenopausal obese women who consume a low calcium diet do not lose bone over a 6‐month period, whether their weight is stable or decreasing moderately.