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Dietary protein alters circulating amino acid (AAs) levels and higher protein intake (HP) is one means of losing weight. We examined 34 overweight and obese women (57 ± 4 years) during 6 months of energy restriction (7.3 ± 3.8% weight loss) divided into groups consuming either normal protein (NP; 18.6 energy% protein) or HP (24.3 energy% protein). There was a reduction in fasting serum glucogenic AAs (p = 0.015) that also associated with greater weight loss (p

To evaluate total and free vitamin D metabolites and hormone-to-prohormone [1,25(OH)2D/25(OH)D] “activation ratio” in PHPT patients with low or insufficient vitamin D status. Thirty female patients with primary hyperparathyroidism (PHPT) and 30 age and body mass index (BMI) matched healthy controls were enrolled. Serum levels of calcium, intact parathyroid hormone (iPTH), vitamin D binding protein (DBP), albumin, total 25(OH)D and 1,25(OH)2D were measured. The activation ratio of vitamin D was calculated as total 1,25(OH)2D/25(OH)D. Calculated serum-free 25(OH)D and 1,25(OH)2D levels were also reported. Compared to the control subject, patients with PHPT had a lower total 25(OH)D and DBP levels (p

When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21–59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health.

BACKGROUND: Hip fractures are associated with a high rate of morbidity and mortality, and successful ambulation after surgery is an important outcome in this patient population. OBJECTIVE: This study aims to determine whether 25-hydroxyvitamin D [25(OH)D] concentration or the Geriatric Nutritional Risk Index (GNRI) is associated with mortality or rates of walking in a patient cohort after hip fracture surgery. METHODS: Patients undergoing hip fracture repair from a multisite study in North America were included. Mortality and mobility were assessed at 30 and 60 d after surgery. Serum albumin, 25(OH)D, and intact parathyroid hormone were measured. Patients were characterized according to 25(OH)D

Objective: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevated parathyroid hormone (PTH) levels with persistently normal calcium levels. The diagnosis of NPHPT assumes the absence of secondary causes of elevated PTH levels. The objective of the current study was to examine levels of free 25-hydroxyvitamin D (25[OH]D) in NPHPT subjects and healthy controls. Methods: Ten NPHPT subjects and 20 controls who were age, sex, race, and body mass index (BMI) matched were examined. The diagnosis of NPHPT was made if subjects had (1) a serum calcium level of 8.6 to 10.4 mg/dL, total 25(OH)D 30 to 40 ng/mL, and intact PTH (iPTH) ≥66 pg/mL; and (2) normal renal and liver function. Serum total 25(OH)D levels were measured by radioimmunoassay, and free 25(OH)D levels were determined using an enzyme-linked immunoassay. Results: Mean age of NPHPT subjects was 59.9 ± 5.4 years, and mean BMI was 28.4 ± 2.3 kg/m2, which was not significantly different from the mean age and BMI of the control subjects. Mean total 25(OH)D level was 31.9 ± 1.7 ng/mL in NPHPT subjects and did not differ from that of the controls (32.7 ± 3.3 ng/mL; P = .52). However, mean free 25(OH)D was 5.0 ± 0.9 pg/mL in NPHPT subjects, which was 20% lower compared to the mean of the controls (6.2 ± 1.3 pg/mL; P = .013). Serum iPTH levels were inversely correlated with levels of measured free 25(OH)D (r = -0.42; P .10). Conclusion: Measured free 25(OH)D levels are lower in NPHPT subjects than in healthy control subjects. We suggest that some NPHPT subjects may actually have secondary hyperparathyroidism based on their free 25(OH) D levels. Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CV = coefficient of variation; DBP = vitamin D-binding protein; iPTH = intact parathyroid hormone; NPHPT = normocalcemic primary hyperparathyroidism.

OBJECTIVE This study aimed to examine change in bone mineral density (BMD) and trabecular bone score among older adult weight regainers (WR) and weight maintainers (WM). METHODS Observational data come from 77 older adults (mean age: 67 [SD 5] years; 69% women; 70% white) with obesity (mean BMI: 33.6 [SD 3.7] kg/m2 ) who lost weight during an 18-month weight loss intervention. Total body mass and body composition, along with regional (total hip, femoral neck, lumbar spine) BMD and trabecular bone score, were measured at baseline, 18 months, and 30 months. WR (n = 36) and WM (n = 41) categories were defined as a ≥ 5% or

Vitamin D may affect cognitive performance, but previous studies are either short term or observational. We conducted a randomized controlled trial of vitamin D supplementation on domain-specific cognitive measures in postmenopausal women. Overweight/obese women with serum 25-hydroxyvitamin D (25OHD) levels less than 30 ng/mL were recruited. Vitamin D3 supplementation (600, 2,000, or 4,000 IU/d) was randomly assigned in a double-blinded manner for 1 year. Serum 25-hydroxyvitamin D, osteocalcin (total and undercarboxylated), amyloid beta, parathyroid hormone, and estradiol were analyzed before and after supplementation. Cognitive tests were administered after treatment. The women (58 ± 6 years; body mass index, 30.0 ± 3.5 kg/m2) had a baseline serum 25-hydroxyvitamin D level of 22.6 ± 5.8 ng/mL that increased to 30.2 ± 5.6, 36.0 ± 4.9, and 40.8 ± 7.0 ng/mL in the 600, 2,000, and 4,000 IU/d groups, respectively (p < .001). Participants taking 2,000 IU/d compared to other doses performed better in learning and memory tests (p < .05), yet the 4,000 IU/d group had a slower reaction time compared to the 600 IU/d group. Multiple regression indicated that serum undercarboxylated osteocalcin predicted tasks associated with reaction time and executive function, whereas body mass index and parathyroid hormone negatively predicted reaction time and executive function (p ≤ .01). These data suggest that vitamin D has differential effects on domain-specific cognitive measures and that a higher dose may negatively affect reaction time.

BACKGROUND: Dietary protein and micronutrients are important to the maintenance of bone health and may be an effective countermeasure to weight-loss–associated bone loss. OBJECTIVES: We aimed to determine the effect of a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan on change in bone density and quality as compared with weight stability in older adults using a randomized post-test design. We hypothesized that participants randomly assigned to this meal plan would maintain similar bone density and quality to weight-stable controls, despite significant reductions in body mass. METHODS: Ninety-six older adults (aged 70.3 ± 3.7 y, 74% women, 27% African American) with obesity [body mass index (kg/m(2)): 35.4 ± 3.3] were randomly assigned to a 6-mo hypocaloric, nutritionally complete, higher-protein meal plan targeting ≥1.0 g protein · kg body weight(–1) · d(–1) [weight-loss (WL) group; n = 47] or to a weight-stability (WS) group targeting 0.8 g protein · kg body weight(–1) · d(–1), the current Recommended Dietary Allowance (n = 49). The primary outcome was total hip bone mineral density (BMD), with femoral neck BMD, lumbar spine BMD, and lumbar spine trabecular bone score (TBS) as secondary outcomes, all assessed at baseline and 3 and 6 mo with dual-energy X-ray absorptiometry. RESULTS: Baseline total hip, femoral neck, and lumbar spine BMDs were 1.016 ± 0.160, 0.941 ± 0.142, and 1.287 ± 0.246 g/cm(2), respectively; lumbar TBS was 1.398 ± 0.109. Despite significant weight loss achieved in the WL group (6.6 ± 0.4 kg; 8.6% ± 0.4% of baseline weight), 6-mo regional BMD estimates were similar to those in the WS group (all P > 0.05). Lumbar spine TBS significantly increased at 6 mo in the WL group (mean: 1.421; 95% CI: 1.401, 1.441) compared with the WS group (1.390: 95% CI: 1.370, 1.409; P = 0.02). CONCLUSIONS: Older adults following a hypocaloric, nutritionally complete, higher-protein meal plan maintained similar bone density and quality to weight-stable controls. Our data suggest that adherence to this diet does not produce loss of hip and spine bone density in older adults and may improve bone quality. This trial was registered at clinicaltrials.gov as NCT02730988.

Background: Vitamin D3 is metabolized to 25-hydroxyvitamin D [25(OH)D] in liver, and only after it goes to kidney is it converted to its biologically active form, 1,25-dihydroxyvitamin D [1,25(OH)2D]. Also, the majority of both total 25(OH)D and 1,25(OH)2D are tightly bound to vitamin D bind protein (DBP) and only a small portion remains in free form. In certain patient populations, like primary hyperparathyroidism (PHPT), concentrations of free vitamin D metabolites may be affected by altered levels of binding protein. Objective: To evaluate total and free 1,25(OH)2D levels in PHPT patients and healthy controls. Methods: Thirty female patients with PHPT and 30 healthy age and body mass index (BMI) matched controls were enrolled (57.1 ± 9.8 years and BMI of 32.2 ± 7.2 kg/m2). Serum levels of calcium, intact parathyroid hormone (iPTH), DBP, total 25(OH)D and 1,25(OH)2D levels were examined. Serum free 25(OH)D and 1,25(OH)2D levels were calculated using equations adapted from Bikle et al. Results: There were no significant differences in age and BMI between groups. Compared to controls, patients with PHPT had lower total 25(OH)D (25.2 ± 7.5 vs. 19.3 ± 6.4 ng/mL; p Conclusion: Postmenopausal patients with PHPT had lower serum total 25(OH)D, but similar free 25(OH)D levels. In contrast, total 1,25(OH)2D levels did not differ between patients and controls; however, patients had higher free 1,25(OH)2D. Because total 25(OH)D and 1,25(OH)2D levels do not reflect free levels, standard clinical measures of circulating vitamin D may not be an accurate estimate of true vitamin D status in patients with PHPT. References: Bikle et al. Serum Protein Binding of 1,25-Dihydroxyvitamin D: A Reevaluation by Direct Measurement of Free Metabolite Levels. JCEM 1985;61:969-75.

Background Menopause is associated with fatty liver, glucose dysregulation, increased body fat, and impaired bone quality. Previously, it was demonstrated that single sessions of high-intensity interval exercise (HIIE) are more effective than distance- and duration-matched continuous exercise (CE) on altering hepatic triglyceride (TG) metabolism and very-low density lipoprotein-TG (VLDL-TG) secretion. Methods Six weeks training using these modalities was examined for effects on hepatic TG metabolism/secretion, glucose tolerance, body composition, and bone mineral density (BMD) in ovariectomized (OVX) and sham-operated (SHAM) mice. OVX and SHAM were assigned to distance- and duration-matched CE and HIIE, or sedentary control. Results Energy expenditure during exercise was confirmed to be identical between CE and HIIE and both similarly reduced post-exercise absolute carbohydrate oxidation and spontaneous physical activity (SPA). OVX vs. SHAM displayed impaired glucose tolerance and greater body fat despite lower hepatic TG, and these outcomes were not affected by training. Only HIIE increased hepatic AMPK in OVX and SHAM, but neither training type impacted VLDL-TG secretion. As expected, BMD was lower in OVX, and training did not affect long bones. Conclusions The results reveal intensity-dependent effects on hepatic AMPK expression and general exercise effects on subsequent SPA and substrate oxidation that is independent of estrogen status. These findings support the notion that HIIE can impact aspects of liver physiology in females while the effects of exercise on whole body substrate selection appear to be independent of training intensity. However, neither exercise approach mitigated the impairment in glucose tolerance and elevated body fat occurring in OVX mice.

BACKGROUND: Alternate day fasting (ADF) is a novel diet therapy that reduces body weight, but its effect on bone health remains unknown. OBJECTIVE: This study examined the impact of ADF versus traditional daily calorie restriction (CR) on markers of bone metabolism in a 6-month randomized controlled trial. METHODS: Overweight and obese subjects (n = 100) were randomized to 1 of 3 groups for 6 months: 1) ADF (25% energy intake fast day, alternated with 125% intake feast day; 2) CR (75% intake every day); or 3) control (usual intake every day). RESULTS: Body weight decreased similarly (P

Background The importance of vitamin D in general health as well as in human reproductive success has been an area of focus. A better understanding of vitamin D metabolism, particularly vitamin D binding protein, is important when elucidating this relationship. Methods This case control trial seeks to characterize vitamin D metabolism in infertile patients undergoing natural cycle IVF as compared to normally cycling premenopausal women with proven fertility matched for age and body mass index (BMI). A total of 68 subjects were examined; 39 were infertile premenopausal women and 29 were regularly cycling fertile controls. Their 25-hydroxy vitamin D (25OHD), vitamin D binding protein (DBP), and albumin were measured and free and bioavailable 25OHD calculated. Between group comparisons were conducted with an unpaired t-test. A stepwise regression using age, BMI, 25OHD, estradiol & albumin in the model were used to determine predictors of DBP. Results Age, BMI, and total 25OHD did not differ between the two groups. However, vitamin D binding protein, free and bioavailable vitamin D were significantly different in the infertile patients as compared to the regularly cycling fertile controls (p

Low circulating 25-hydroxyvitamin D (25OHD) is commonly found in obese individuals and is often attributed to a volume dilution effect of adipose tissue. However, low vitamin D (LD) intake may contribute to the obesity itself. In this study, we examine whether low vitamin D status contributes to increased food intake and weight gain and can be explained by altered brain serotonin metabolism in 8-month-old female C57BL/6J mice. In a first experiment, mice were fed a 45% high-fat diet (HFD) containing different amounts of vitamin D at low (100 IU/kg), normal (1,000 IU/kg) or high (10,000 IU/kg) intake. After 10 weeks, mice fed LD had greater energy intake, weight gain, total and hepatic fat than the higher vitamin D groups (P < .05). In a second experiment, mice were examined for the central serotonin regulation of food intake after a 10% normal-fat diet (NFD) or 45% HFD containing low (100 IU/kg) or normal (1000 IU/kg) vitamin D. After 10 weeks, both HFD and LD diets attenuated circulating 25OHD concentration. Additionally, LD intake lowered cortical serotonin level, regardless of dietary fat intake (P < .05). In the arcuate and raphe nuclei, gene expression of vitamin D 1α-hydroxylase was lower due to LD during HFD feeding (P < .05). Tryptophan hydroxylase-2 and serotonin reuptake transporter gene expression was not altered due to LD. Overall, these findings suggest that a LD diet alters peripheral 25OHD, reduces central serotonin, and may contribute to weight gain in an obesogenic environment.

OBJECTIVES: Hip fractures are associated with a high rate of morbidity and mortality, and successful ambulation after surgery is an important outcome in this patient population. This study aims to determine whether 25-hydroxyvitamin D (25(OH)D) or the Geriatric Nutritional Risk Index (GNRI) is associated with short term mortality or ability to walk after hip fracture surgery. METHODS: Patients undergoing hip fracture repair were included in this study. Mortality and walking ability were assessed at 30 and 60 days after hip fracture surgery. Pre-operative serum albumin and 25(OH)D were measured. Patients were characterized with 25(OH)D

Objective: To evaluate vitamin D binding protein and free 25-hydroxyvitamin D [25(OH)D] levels in healthy controls compared to primary hyperparathyroidism (PHPT) patients, and to examine PHPT before and after surgery.Methods: Seventy-five PHPT patients and 75 healthy age, gender, and body mass index (BMI) -matched control subjects were examined. In addition, 25 PHPT patients underwent parathyroidectomy and had a 3-month follow up visit. Levels of total and free 25(OH)D, DBP, and intact parathyroid hormone (iPTH) were determined before and 3 months after surgery.Results: There was no significant difference in age and BMI between PHPT patients and controls. Levels of 25(OH)D and DBP were lower in PHPT patients compared to controls (p < 0.01). There was no significant difference in calculated free and bioavailable 25(OH)D levels between PHPT patients and controls. Calcium and iPTH levels decreased to normal but DBP and DBP-bound-25(OH)D increased (P < 0.001) after parathyroidectomy. Levels of DBP were inversely correlated with iPTH (r = −0.406, P < 0.001) and calcium levels (r = −0.423, P < 0.001).Conclusion: Serum DBP levels were lower in patients with PHPT and parathyroidectomy restored DBP levels. We suggest that lower DBP levels is one of contributing mechanisms of low total 25(OH)D in PTHP patients and the total 25(OH)D levels might not reflect true vitamin D status in PHPT patients.

OBJECTIVES: Serum calcidiol is inversely associated with BMI in obese individuals and murine research has shown that vitamin D deficient diets (VDD) increase body weight. Alcohol intake doesn't necessarily increase body weight despite its caloric density but has been associated with VDD. The objective of this study was to determine the effect of vitamin D deficiency with or without alcohol on body weight, body composition, glucose tolerance, and energy expenditure in seven-month-old female mice. METHODS: Seven-month-old female retired breeder C57BL/6J mice (n = 40) were weight-matched and randomized to one of four diets: control (normal purified AIN-93 diet), vitamin D deficient (VDD, 0 intake of vitamin D), alcohol (Alc, 10% ethanol), or vitamin D deficient and alcohol (VDD + Alc). Mice were fed ad libitum for 8 weeks. Body weight and food intake were recorded weekly and body composition was measured at baseline and final time points using EchoMRI. Glucose tolerance and energy expenditure (EE) were assessed by an oral glucose tolerance test (OGTT) and Oxymax/CLAMS unit at week 8. RESULTS: Body weight at baseline was 27.4 ± 1.8 g and did not differ between groups. Mice drinking alcohol had a decreased food intake (p

Diet induced obesity has been shown to reduce bone mineral density (BMD) and Ca absorption. However, previous experiments have not examined the effect of high fat diet (HFD) in the absence of obesity or addressed the type of dietary fatty acids. The primary objective of this study was to determine the effects of different types of high fat feeding, without obesity, on fractional calcium absorption (FCA) and bone health. It was hypothesized that dietary fat would increase FCA and reduce BMD. Mature 8-month-old female C57BL/6J mice were fed one of three diets: a HFD (45% fat) enriched either with monounsaturated fatty acids (MUFAs) or with saturated fatty acids (SFAs), and a normal fat diet (NFD; 10% fat). Food consumption was controlled to achieve a similar body weight gain in all groups. After 8wk, total body bone mineral content and BMD as well as femur total and cortical volumetric BMD were lower in SFA compared with NFD groups (P < 0.05). In contrast, femoral trabecular bone was not affected by the SFAs, whereas MUFAs increased trabecular volume fraction and thickness. The rise over time in FCA was greater in mice fed HFD than NFD and final FCA was higher with HFD (P < 0.05). Intestinal calbindin-D9k gene and hepatic cytochrome P450 2r1 protein levels were higher with the MUFA than the NFD diet (P < 0.05). In conclusion, HFDs elevated FCA overtime; however, an adverse effect of HFD on bone was only observed in the SFA group, while MUFAs show neutral or beneficial effects.

To evaluate the measured free 25-hydroxyvitamin D [25(OH)D] levels in patients with hyperparathyroidism (PHPT) and healthy controls. Eighty patients with PHPT(n = 40) and age and BMI matched controls (n = 40) were examined. Serum levels of total or free 25(OH)D, vitamin D binding protein (DBP), intact parathyroid hormone (iPTH) and calcium were measured. There was no significant difference in age (61.2 ± 11.9 vs 60.2 ± 7.0 years) and BMI (30.0 ± 6.1 vs 30.0 ± 2.2 kg/m2) between PHPT patients and healthy subjects. Levels of total 25(OH)D were about 20 % lower in PHPT patients (26.4 ± 7.7 ng/mL) compared to controls (31.0 ± 7.8 ng/mL, P < 0.05). There were no significant differences in calculated or measured free 25(OH)D levels between PHPT patients (4.9 ± 1.8 or 4.9 ± 1.6 pg/mL, respectively) and control subjects (5.1 ± 1.2 or 5.3 ± 1.6 pg/mL, respectively). Levels of free 25(OH)D were positively associated with levels of total 25(OH)D (r = 0.28, P < 0.05) but negatively correlated with iPTH and calcium levels (r=-0.22 and -0.23 respectively, P < 0.05). Serum total 25(OH)D levels were lower but the calculated or measured free 25(OH)D levels in patients with PHPT did not differ from healthy subjects. We suggest that total 25(OH)D levels may not reflect true vitamin D nutritional status in patients with PHPT.

Obesity induced by high-fat diets (HFDs) is inversely associated with vitamin D status and bone health. However, the associations and effects of excessive fat intake on hepatic and renal vitamin D metabolism have not been addressed. The primary objective was to determine if excessive energy and fat intake, or the type of fat, affects serum 25-hydroxycholecalciferol concentration and whether this can be explained by an alteration of vitamin D-regulating enzymes in older mice. The second objective was a follow up of our recent findings that a high intake of monounsaturated fatty acids (MUFA) is not detrimental to bone in lean mice and whether this is also true under conditions of diet-induced obesity. In the study, twenty-one 8-month-old female C57BL/6 J mice were fed ad libitum for 10 weeks with a 10% normal-fat diet (NFD) or 45% HFD enriched with MUFA or saturated fatty acids (SFA). We found that the HFD, compared with NFD, resulted in greater energy intake, weight gain, total body fat, and liver fat (P < .05). Only the high SFA feeding resulted in higher mRNA but lower protein abundance of hepatic Cyp2r1 and lower renal Cyp24a1 mRNA expression than the NFD group (P < .05). Moreover, although bone mineral density did not differ among groups, the percent difference compared with NFD was significantly lower for SFA (P < .05) but not MUFA. Also, femoral trabecular bone volume fraction was lower (P < .05) only in the SFA compared with the NFD group. In conclusion, high SFA and MUFA feeding differentially affected gene and protein expressions of major vitamin D hydroxylases compared with NFD, but this was unrelated to the lower circulating 25-hydroxycholecalciferol concentration. In addition, only the SFA diet alters vitamin D metabolism and bone changes, indicating the importance of dietary fat composition.

Although much is known about magnesium, its interactions with calcium and vitamin D are less well studied. Magnesium intake is low in populations who consume modern processed-food diets. Low magnesium intake is associated with chronic diseases of global concern [e.g., cardiovascular disease (CVD), type 2 diabetes, metabolic syndrome, and skeletal disorders], as is low vitamin D status. No simple, reliable biomarker for whole-body magnesium status is currently available, which makes clinical assessment and interpretation of human magnesium research difficult. Between 1977 and 2012, US calcium intakes increased at a rate 2-2.5 times that of magnesium intakes, resulting in a dietary calcium to magnesium intake ratio of >3.0. Calcium to magnesium ratios 2.8 can be detrimental, and optimal ratios may be ∼2.0. Background calcium to magnesium ratios can affect studies of either mineral alone. For example, US studies (background Ca:Mg >3.0) showed benefits of high dietary or supplemental magnesium for CVD, whereas similar Chinese studies (background Ca:Mg

Background: Data have shown that healthy children and adolescents have an inadequate intake of zinc, an essential nutrient for growth. It is unclear whether zinc supplementation can enhance bone health during this rapid period of growth and development. Objective: The primary aim of this study was to determine the effect of zinc supplementation on biochemical markers of bone turnover and growth in girls entering the early stages of puberty. The secondary aim was to test moderation by race, body mass index (BMI) classification, and plasma zinc status at baseline. Methods: One hundred forty seven girls aged 9–11 y (46% black) were randomly assigned to a daily oral zinc tablet (9 mg elemental zinc; n = 75) or an identical placebo (n = 72) for 4 wk. Fasting plasma zinc, procollagen type 1 amino-terminal propeptide (P1NP; a bone formation marker), carboxy-terminal telopeptide region of type 1 collagen (ICTP; a bone resorption marker), and insulin-like growth factor I (IGF-I) were assessed at baseline and post-test. Additional markers of bone formation (osteocalcin) and resorption (urinary pyridinoline and deoxypyridinoline) were also measured. Results: Four weeks of zinc supplementation increased plasma zinc concentrations compared with placebo [mean change, 1.8 μmol/L (95% CI: 1.0, 2.6) compared with 0.2 μmol/L (95% CI: −0.3, 0.7); P < 0.01]. Zinc supplementation also increased serum P1NP concentrations compared with placebo [mean change, 23.8 μmol/L (95% CI: −14.9, 62.5) compared with −31.0 μmol/L (95% CI: −66.4, 4.2); P = 0.04). There was no effect from zinc supplementation on osteocalcin, ICTP, pyridinoline, deoxypyridinoline, or IGF-I. There was no moderation by race, BMI classification, or plasma zinc status at baseline. Conclusions: Our data suggest that 4 wk of zinc supplementation increases bone formation in premenarcheal girls. Further studies are needed to determine whether supplemental zinc can improve childhood bone strength. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT01892098","term_id":"NCT01892098"}}NCT01892098.

Low calcium absorption is associated with low bone mass and fracture. In this study, we use gold standard methods of fractional calcium absorption (FCA) to determine whether polymorphisms of intestinal receptors, vitamin D receptor (VDR) and estrogen receptor α (ESR1), influence the response to energy restriction. Fractional calcium absorption was measured using dual stable isotopes ((42)Ca and (43)Ca) in women given adequate calcium and vitamin D and examined at baseline and after 6 weeks of energy restriction or no intervention. After genotyping, the relationship between VDR and ESR1 genotypes/haplotypes and FCA response was assessed using several genetic models. One-hundred and sixty-eight women (53 ± 11 years of age) were included in this analysis. The ESR1 polymorphisms, PvuII and XbaI and VDR polymorphisms (TaqI, ApaI) did not significantly influence FCA. The BB genotype of the VDR polymorphism, BsmI, was associated with a greater decrease in FCA than the Bb/bb genotype. Multiple linear regression showed that the BsmI polymorphism or the VDR haplotype, BAt, in addition to changes in weight and vitamin D intake explained ~16% of the variation in changes in FCA. In conclusion, the reduction in calcium absorption due to energy restriction is greatest for those with the BB genotype. Previous candidate gene studies show that VDR polymorphisms are associated with higher risk for osteoporosis, and the current study supports the notion that the BsmI polymorphism in intestinal VDR may be contributing to alterations in bone health.

To examine the relationship between endogenous serum estradiol and vitamin D-binding protein (DBP) and total, free, and bioavailable 25-hydroxyvitamin D (25OHD) concentrations in pre- and postmenopausal women.In 165 healthy women (ages, 26 to 75 years) not taking any form of exogenous estrogen, the serum concentrations of estradiol, 25OHD, DBP, parathyroid hormone, and albumin were measured. Free and bioavailable 25OHD (free + albumin-bound) levels were calculated from total 25OHD, DBP, and serum albumin levels.Premenopausal women had higher serum 25OHD (31.5 ± 7.9 ng/mL), DBP (45.3 ± 6.2 mg/dL), and estradiol (52.8 ± 35.0 pg/mL) levels than postmenopausal women (26.5 ± 4.9 ng/mL, 41.7 ± 5.7 mg/dL, and 12.9 ± 4.9 pg/mL), respectively. In addition, the calculated free and bioavailable 25OHD levels were higher in pre- than postmenopausal women (P.05). Serum estradiol correlated with DBP (r = 0.22; P.01) and total 25OHD (r = 0.27; P.01). In multivariate regression models (with or without serum 25OHD), estradiol was independently associated with DBP (P.05).Lower estradiol level is one of the factors that contribute to lower DBP levels in older women. Our data indicate that besides well-known factors such as age, gender, and race, serum estradiol concentrations are also a physiologic predictor of DBP concentration.

The effect of vitamin D supplementation and caloric restriction (CR) on glycemic indices and osteocalcin (OC) is not clear. In this randomized controlled double blind trial, we examined whether vitamin D3 supplementation at 2500 IU/d (D) or placebo has differential effects on markers of insulin sensitivity and bone turnover in overweight/obese postmenopausal women during 6 weeks of caloric restriction (weight loss; WL, n = 39) compared to weight maintenance (WM, n = 37). Seventy-six women (57 ± 6 years) completed this study and the WL groups lost 4 ± 1% of body weight. Baseline serum 25-hydroxyvitamin D (25OHD) was 24.8 ± 5.6 ng/mL at baseline; the rise was greatest in WL-D group (p < 0.05). There was an interaction between vitamin D intake and weight on serum OC, insulin, glucose and markers of insulin sensitivity (p < 0.05). The change in OC was explained by changes in serum 25OHD and insulin (model R 2 = 25.6%). Overall, vitamin D supplementation and CR influence serum osteocalcin levels and modestly favor improvements in insulin sensitivity.

Diet-induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta-analysis (using a random-effects model) to quantify the effect of diet-induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight-loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual-energy X-ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet-induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm2 in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], –0.014 to –0.005, –0.021 to –0.008, and –0.024 to –0.000 g/cm2, at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet-induced weight loss on lumbar spine or whole-body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (–0.011 g/cm2; 95% CI, –0.018 to –0.003 g/cm2) after 6 months. Although no statistically significant changes occurred in serum concentrations of N-terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L; 95% CI, 0.13 to 0.39 nmol/L), C-terminal telopeptide of type I collagen (CTX) (4.72 nmol/L; 95% CI, 2.12 to 7.30 nmol/L) or N-terminal telopeptide of type I collagen (NTX) (3.70 nmol/L; 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet-induced weight loss to promote bone breakdown. These data show that in overweight and obese individuals, a single diet-induced weight-loss intervention induces a small decrease in total hip BMD, but not lumbar spine BMD. This decrease is small in comparison to known metabolic benefits of losing excess weight. © 2015 American Society for Bone and Mineral Research

Background: Weight loss (WL) negatively affects bone mineral density (BMD) in older populations and has specifically been shown in women. Objective: In this prospective controlled trial, we examined variables of bone quality and endocrine changes after intentional WL in men. Design: Thirty-eight overweight and obese [mean ± SD body mass index (in kg/m2): 31.9 ± 4.4; age: 58 ± 6 y] men were recruited to either WL through caloric restriction or weight maintenance (WM) for 6 mo. Results: There was a −7.9 ± 4.4% and +0.2 ± 1.6% change in body weight in the WL and WM groups, respectively. There was a greater increase in femoral neck and total body BMD and bone mineral content (BMC) in the WM group than in the WL group (P-interaction effect < 0.05). In contrast, there was a trend for the tibia cortical thickness and area to decrease more in the WM group than in the WL group (P ≤ 0.08). There was a decrease in the periosteal circumference in both groups over time (P < 0.01) and no statistically significant changes in trabecular bone. Circulating total, free, and bioavailable estradiol decreased in the WL group compared with the WM group, and changes were different between groups (P < 0.05). Serum total and bioavailable testosterone increased in both groups (P < 0.01). Serum 25-hydroxyvitamin D increased to a similar extent in both groups (P < 0.05). Conclusions: Moderate WL in overweight and obese men did not decrease BMD at any anatomical site or alter cortical and trabecular bone and geometry. Also, despite increased BMD at some sites when maintaining excess body weight, cortical bone showed a trend in the opposite direction. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00472745","term_id":"NCT00472745"}}NCT00472745.

Animal studies indicate Salacia reduces body weight, possibly due to its α-glucosidase inhibitor (α-GI) properties, but this has not been examined previously. In this study, a randomized, placebo-controlled, three-way cross-over design was used to evaluate whether Salacia Chinensis (SC) reduces appetite in healthy overweight/obese individuals (body mass index 28.8 ±3.6 kg/m2; 32 ± 12 years). Forty-eight participants were fasted overnight and consumed a dose of SC (300 or 500 mg) or placebo with a fixed breakfast meal at each visit. Appetite sensations, glycemic indices and gastrointestinal peptides were measured. Results indicated that SC had no effect on postprandial appetite. However, in women, hunger was reduced by SC compared to placebo at multiple time points (300 mg; p < 0.05), but not in men. Area under the curve (AUC) for serum glucose, insulin and amylin was attenuated with SC compared to placebo (p < 0.05). Glucagon like peptide-1 had two peaks after the meal, but the AUC did not differ between groups. The AUC of peak areas for peptide YY and ghrelin were greater for SC than placebo (p < 0.05). These findings indicate that Salacia decreases glycemic indices supporting its role as an α-GI, and affects certain gastrointestinal peptides suggesting it may be an appetite modulator.

Objective: To determine whether low levels of vitamin D-binding protein (DBP) are related to 25-hydroxyvitamin D (25[OH]D) deficiency in female patients with primary hyperparathyroidism (PHPT). Methods: Twenty-five female patients with PHPT (serum calcium level >10.2 mg/dL and intact parathyroid hormone (iPTH) level >66 pg/mL) and 25 healthy age- and body mass index-matched female control subjects were enrolled. Serum calcium and iPTH levels were determined by commercial laboratories. Levels of 25(OH)D and 1,25-dihydroxyvitamin D (1,25[OH] 2 D) were determined by radioimmunoassay, and DBP level was determined by enzyme-linked immunosorbent assay. Results: Serum iPTH and calcium levels were higher in PHPT patients than control subjects (P

Objective To review the current literature investigating the association of plasma parathyroid hormone (PTH) with the prevalence of metabolic syndrome and the risk for cardiovascular disease (CVD). Methods We conducted a search of PubMed and Medline database using the terms hyperparathyroidism, metabolic syndrome, hypertension, hyperlipidemia, hyper-glycemia, and CVD. We reviewed relevant studies from 2004 to 2012. Results The current literature assessing the association of plasma PTH levels with metabolic syndrome and CVD is inconsistent; however, positive associations among hyperparathyroidism, metabolic syndrome, and CVD were found in a majority of the studies. The differences in the study populations may partly explain the mixed results. Conclusion In the general population, a high serum PTH level predisposes patients to CVD mortality. Further research is needed to determine the role of PTH in the etiology of metabolic syndrome and CVD. (Endocr Pract. 2013;19:712-717)

Obesity is associated with lower serum concentrations of 25-hydroxyvitamin D (25OHD) and higher intact PTH. The threshold of 25OHD needed to maximally suppress intact PTH has been suggested as a marker of optimal vitamin D status.In this study, we hypothesized that whereas the obese have a higher serum PTH and lower 25OHD, suppression of serum PTH by 25OHD would be independent of body weight.We performed a retrospective analysis on 383 women (ages 24-75 y) with a wide range of body weights (43-185 kg) who were stabilized to 1-1.2 g calcium/d for 1 month before blood draw. Body composition, serum PTH, 25OHD, calcium, and creatinine were measured. Locally weighted regression and smoothing scatterplots were used to depict the association between serum PTH and 25OHD. A nonlinear exponential model determined the point for near maximal suppression of PTH by 25OHD.The point for near maximal suppression of PTH by 25OHD for all women (body mass index, 31.4 ± 7.7 kg/m²) occurred at a 25OHD concentration of 21.7 ng/mL (95% confidence interval, 28-48 ng/mL). No point of maximal suppression was found for nonobese women, yet in the obese women (n = 207; body mass index,30 kg/m²) suppression of PTH occurred at a 25OHD concentration of 11.1 ng/mL (95% confidence interval, 4.7-17.5 ng/mL).These results suggest that if PTH is suppressed at a lower serum 25OHD in the obese compared to the entire population, the lower average 25OHD concentrations in the obese may not have the same physiological significance as in the general population.

Background: Weight loss (WL) is associated with a decrease in calcium absorption and may be one mechanism that induces bone loss with weight reduction. Objective: Because vitamin D supplementation has been shown to increase true fractional calcium absorption (TFCA), the goal of this study was to examine the effect of vitamin D during WL or weight maintenance (WM). Design: A randomized, placebo-controlled, double-blind 6-wk study was conducted in 82 postmenopausal women [BMI (in kg/m2; ±SD): 30.2 ± 3.7] with 25-hydroxyvitamin D [25(OH)D] concentrations

To evaluate free and bioavailable 25-hydroxyvitamin D (25[OH]D) levels in primary hyperparathyroidism (PHPT) patients.Fifty PHPT patients and 50 healthy age-, gender-, and body mass index (BMI)-matched control subjects were enrolled. Levels of 25(OH)D were determined by a radioimmunoassay and vitamin D-binding protein (DBP) were determined by an enzyme-linked immunosorbent assay. Free and bioavailable 25(OH)D were calculated utilizing equations that use average binding coefficients for DBP and albumin.There was no significant difference in age and BMI between PHPT patients and controls (P.05). Levels of 25(OH)D, DBP, and DBP-bound 25(OH)D were lower in PHPT patients compared to controls (P.01). There was no significant difference in free and bioavailable 25(OH)D levels between PHPT patients and controls (P.05). Levels of intact parathyroid hormone were inversely correlated with free (r = -0.217; P.05) and bioavailable 25(OH)D levels (r = -0.296; P.01).Serum total 25(OH)D levels were lower, while free and bioavailable 25(OH)D remained similar in patients with PHPT compared to controls. We suggest that low 25(OH)D levels might not reflect true vitamin D nutrition status in PHPT patients.25(OH)D = 25-hydroxyvitamin D BMI = body mass index DBP = vitamin D-binding protein iPTH = intact parathyroid hormone PHPT = primary hyperparathyroidism.

Accumulating evidence supports a complex relationship between adiposity and osteoporosis in overweight/obese individuals, with local interactions and endocrine regulation by adipose tissue on bone metabolism and fracture risk in elderly populations. This review was conducted to summarize existing evidence to test the hypothesis that obesity is a risk factor for bone health in aging individuals. Mechanisms by which obesity adversely affects bone health are believed to be multiple, such as an alteration of bone-regulating hormones, inflammation, oxidative stress, the endocannabinoid system, that affect bone cell metabolism are discussed. In addition, evidence on the effect of fat mass and distribution on bone mass and quality is reviewed together with findings relating energy and fat intake with bone health. In summary, studies indicate that the positive effects of body weight on bone mineral density cannot counteract the detrimental effects of obesity on bone quality. However, the exact mechanism underlying bone deterioration in the obese is not clear yet and further research is required to elucidate the effect of adipose depots on bone and fracture risk in the obese population.

Background: Considerable attention has recently focused on dietary protein's role in the mature skeleton, prompted partly by an interest in nonpharmacologic approaches to maintain skeletal health in adult life.Objective: The aim was to conduct a systematic review and meta-analysis evaluating the effects of dietary protein intake alone and with calcium with or without vitamin D (Ca±D) on bone health measures in adults.Design: Searches across 5 databases were conducted through October 2016 including randomized controlled trials (RCTs) and prospective cohort studies examining 1) the effects of "high versus low" protein intake or 2) dietary protein's synergistic effect with Ca±D intake on bone health outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments. Strength of evidence was rated by group consensus. Random-effects meta-analyses for outcomes with ≥4 RCTs were performed.Results: Sixteen RCTs and 20 prospective cohort studies were included in the systematic review. Overall ROB was medium. Moderate evidence suggested that higher protein intake may have a protective effect on lumbar spine (LS) bone mineral density (BMD) compared with lower protein intake (net percentage change: 0.52%; 95% CI: 0.06%, 0.97%, I2: 0%; n = 5) but no effect on total hip (TH), femoral neck (FN), or total body BMD or bone biomarkers. Limited evidence did not support an effect of protein with Ca±D on LS BMD, TH BMD, or forearm fractures; there was insufficient evidence for FN BMD and overall fractures.Conclusions: Current evidence shows no adverse effects of higher protein intakes. Although there were positive trends on BMD at most bone sites, only the LS showed moderate evidence to support benefits of higher protein intake. Studies were heterogeneous, and confounding could not be excluded. High-quality, long-term studies are needed to clarify dietary protein's role in bone health. This trial was registered at www.crd.york.ac.uk as CRD42015017751.

To examine the effect of exercise modality during weight loss on hip and spine bone mineral density (BMD) in overweight and obese, older adults.This analysis compared data from two 5-month, randomized controlled trials of caloric restriction (CR; inducing 5-10% weight loss) with either resistance training (RT) or aerobic training (AT) in overweight and obese, older adults. Participants in the RT + CR study underwent 3 days/week of 8 upper/lower body exercises (3 sets, 10 repetitions at 70% 1 RM) and participants in the AT+CR study underwent 4 days/week of treadmill walking (30 min at 65-70% heart rate reserve). BMD at the total hip, femoral neck, and lumbar spine was assessed via dual-energy X-ray absorptiometry at baseline and 5 months.A total of 123 adults (69.4 ± 3.5 years, 67% female, 81% Caucasian) participated in the RT+CR (n = 60) and AT+CR (n = 63) interventions. Average weight loss was 5.7% (95% CI: 4.6-6.7%) and 8.2% (95% CI: 7.2-9.3%) in RT+CR and AT+CR groups, respectively. After adjustment for age, gender, race, baseline BMI and BMD, and weight change, differential treatment effects were observed for total hip and femoral neck (both p.05), but not lumbar spine. Total hip (1.83 [-3.90, 7.55] mg/cm2) and femoral neck (9.14 [-0.70, 18.98] mg/cm2) BMD was unchanged in RT+CR participants, and modestly decreased in AT+CR participants (total hip: -7.01 [-12.73, -1.29] mg/cm2; femoral neck: -5.36 [-14.92, 4.20] mg/cm2).Results suggest performing resistance, rather than aerobic, training during CR may attenuate loss of hip and femoral neck BMD in overweight and obese older adults. Findings warrant replication from a long-term, adequately powered, RCT.

The effects of higher than recommended vitamin D doses on bone mineral density (BMD) and quality are not known. In this study, higher intakes, in postmenopausal women undergoing weight control over 1 year, had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry. Studies examining how bone responds to a standard dose of vitamin D supplementation have been inconsistent. In addition, the effects of higher doses on BMD and quality are not known. Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance. This 1-year-long, randomized, double-blind controlled study addresses whether vitamin D supplementation, in healthy overweight/obese older women, affects BMD and bone structural parameters. In addition, bone turnover and serum total, free, and bioavailable 25-hydroxyvitamin D (25OHD) responses to one of three daily levels of vitamin D3 (600, 2000, 4000 IU) with 1.2 Ca g/day during weight control were examined. Fifty-eight women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m2, serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p

Removal of the parametrial fat pads (partial lipectomy) from female SKH-1 mice fed a high-fat diet inhibited UVB-induced carcinogenesis, but this was not observed in mice fed a low-fat chow diet. Partial lipectomy in high-fat–fed mice decreased the number of keratoacanthomas and squamous cell carcinomas per mouse by 76 and 79%, respectively, compared with sham-operated control mice irradiated with UVB for 33 wk. Immunohistochemical analysis indicated that partial lipectomy increased caspase 3 (active form) positive cells by 48% in precancerous epidermis away from tumors, by 68% in keratoacanthomas, and by 224% in squamous cell carcinomas compared with sham-operated control mice. In addition, partial lipectomy decreased cell proliferation away from tumors and in tumors. RT-PCR analysis for adipokines revealed that mRNAs for TIMP1, MCP1, and SerpinE1 (proinflammatory/antiapoptotic cytokines) in the parametrial fat pads of sham-operated control mice were 54- to 83-fold higher than levels in compensatory fat that returned after surgery in partially lipectomized mice at the end of the tumor study. Feeding mice high-fat diets for 2 wk increased levels of TIMP1 and other adipokines in serum and epidermis, and these increases were inhibited by removal of the parametrial fat pads. Our results are a unique demonstration that surgical removal of a specific tissue fat results in inhibition of carcinogenesis in obese mice. This inhibition was associated with an increase in apoptosis and a decrease in proliferation in tumors and in precancerous areas away from tumors.

We recently showed that excessive fructose consumption, already associated with numerous metabolic abnormalities, reduces rates of intestinal Ca(2+) transport. Using a rat lactation model with increased Ca(2+) requirements, we tested the hypothesis that mechanisms underlying these inhibitory effects of fructose involve reductions in renal synthesis of 1,25-(OH)(2)D(3). Pregnant and virgin (control) rats were fed isocaloric fructose or, as controls, glucose, and starch diets from d 2 of gestation to the end of lactation. Compared to virgins, lactating dams fed glucose or starch had higher rates of intestinal transcellular Ca(2+) transport, elevated intestinal and renal expression of Ca(2+) channels, Ca(2+)-binding proteins, and CaATPases, as well as increased levels of 25-(OH)D(3) and 1,25-(OH)(2)D(3). Fructose consumption prevented almost all of these lactation-induced increases, and reduced vitamin D receptor binding to promoter regions of Ca(2+) channels and binding proteins. Changes in 1,25-(OH)(2)D(3) level were tightly correlated with alterations in expression of 1α-hydroxylase but not with levels of parathyroid hormone and of 24-hydroxylase. Bone mineral density, content, and mechanical strength each decreased with lactation, but then fructose exacerbated these effects. When Ca(2+) requirements increase during lactation or similar physiologically challenging conditions, excessive fructose consumption may perturb Ca(2+) homeostasis because of fructose-induced reductions in synthesis of 1,25-(OH)(2)D(3).

Menopause and increasing age are associated with a decrease in calcium absorption that can contribute to the pathogenesis of osteoporosis. We hypothesized that alendronate plus vitamin D3 (ALN + D) would increase fractional calcium absorption (FCA). In this randomized, double-blind, placebo-controlled multicenter clinical trial, 56 postmenopausal women with 25-hydroxyvitamin D [25(OH)D] concentrations of 25 ng/mL or less and low bone mineral density (BMD) received 5 weekly doses of placebo or alendronate 70 mg plus vitamin D3 2800 IU (ALN + D). Calcium intake was stabilized to approximately 1200 mg/d prior to randomization. FCA was determined using a dual-tracer stable-calcium isotope method. FCA and 25(OH)D were similar between treatment groups at baseline (0.31 ± 0.12 ng/mL and 19.8 ± 4.7 ng/mL, respectively). After 1 month of treatment, subjects randomized to ALN + D experienced a significant least squares (LS) mean [95% confidence interval (CI)] increase in FCA [0.070 (0.042, 0.098)], whereas FCA did not change significantly in the placebo group [−0.016 (−0.044, 0.012)]. After ALN + D treatment, patients had higher 25(OH)D levels (LS mean difference 7.3 ng/mL, p

Brassinosteroids are plant-derived polyhydroxylated derivatives of 5a-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids, with no known function in mammals. 28-Homobrassinolide (HB), a steroidal lactone with potent plant growth-promoting property, stimulated protein synthesis and inhibited protein degradation in L6 rat skeletal muscle cells (EC50 4 μM) mediated in part by PI3K/Akt signaling pathway. Oral administration of HB (20 or 60 mg/kg/d for 24 d) to healthy rats fed normal diet (protein content 23.9%) increased food intake, body weight gain, lean body mass, and gastrocnemius muscle mass as compared with vehicle-treated controls. The effect of HB administration increased slightly in animals fed a high-protein diet (protein content 39.4%). Both oral (up to 60 mg/kg) and subcutaneous (up to 4 mg/kg) administration of HB showed low androgenic activity when tested in the Hershberger assay. Moreover, HB showed no direct binding to the androgen receptor in vitro. HB treatment was also associated with an improved physical fitness of untrained healthy rats, as evident from a 6.7% increase in lower extremity strength, measured by grip test. In the gastrocnemius muscle of castrated animals, HB treatment significantly increased the number of type IIa and IIb fibers and the cross-sectional area of type I and type IIa fibers. These findings suggest that oral application of HB triggers selective anabolic response with minimal or no androgenic side-effects and begin to elucidate the putative cellular targets for plant brassinosteroids in mammals.—Esposito, D., Komarnytsky, S., Shapses, S., Raskin, I. Anabolic effect of plant brassinosteroid.

Our previous studies reported that caffeine or voluntary exercise decreased skin tumor multiplicity, in part, by decreasing fat levels in the dermis. These data suggest that tissue fat may play an important role in regulating ultraviolet light (UV) B-induced skin tumor development. In the present study, we explored the effects of high-fat diets rich in either omega-3 or omega-6 fatty acids on UVB-induced skin carcinogenesis. SKH-1 mice were irradiated with 30 mJ/cm(2) of UVB once a day, two times per week for 39 weeks. During UVB treatment, one group of mice was given a high-fat fish oil (HFFO) diet rich in omega-3 fatty acids and the other group of mice was given a high-fat mixed-lipids (HFMLs) diet rich in omega-6 fatty acids. The results showed that, compared with HFML diet, HFFO treatment (i) increased latency for the development of UVB-induced skin tumors; (ii) decreased the formation of papilloma, keratoacanthoma and carcinoma by 64, 52 and 46%, respectively and (iii) decreased the size of papilloma, keratoacanthoma and carcinoma by 98, 80 and 83%, respectively. Mechanistic studies with antibody array revealed that compared with HFML diet, administration of HFFO to the mice significantly decreased the UVB-induced increases in the levels of TIMP-1, LIX and sTNF R1 as well as other several proinflammatory cytokines and stimulated the UVB-induced apoptosis in the epidermis. Our results indicate that omega-3 fatty acids in HFFO diet have beneficial effects against UVB-induced skin carcinogenesis, and these effects may be associated with an inhibition on UVB-induced inflammatory response.

The Institute of Medicine Committee to Review Dietary Reference Intakes for Calcium and Vitamin D comprehensively reviewed the evidence for both skeletal and nonskeletal health outcomes and concluded that a causal role of calcium and vitamin D in skeletal health provided the necessary basis for the 2011 Estimated Average Requirement (EAR) and Recommended Dietary Allowance (RDA) for ages older than 1 year. For nonskeletal outcomes, including cancer, cardiovascular disease, diabetes, infections, and autoimmune disorders, randomized clinical trials were sparse, and evidence was inconsistent, inconclusive as to causality, and insufficient for Dietary Reference Intake (DRI) development. The EAR and RDA for calcium range from 500 to 1,100 and 700 to 1,300 mg daily, respectively, for ages 1 year and older. For vitamin D (assuming minimal sun exposure), the EAR is 400 IU/day for ages older than 1 year and the RDA is 600 IU/day for ages 1 to 70 years and 800 IU/day for 71 years and older, corresponding to serum 25-hydroxyvitamin D (25OHD) levels of 16 ng/mL (40 nmol/L) for EARs and 20 ng/mL (50 nmol/L) or more for RDAs. Prevalence of vitamin D inadequacy in North America has been overestimated based on serum 25OHD levels corresponding to the EAR and RDA. Higher serum 25OHD levels were not consistently associated with greater benefit, and for some outcomes U-shaped associations with risks at both low and high levels were observed. The Tolerable Upper Intake Level for calcium ranges from 1,000 to 3,000 mg daily, based on calcium excretion or kidney stone formation, and from 1,000 to 4,000 IU daily for vitamin D, based on hypercalcemia adjusted for uncertainty resulting from emerging risk relationships. Urgently needed are evidence-based guidelines to interpret serum 25OHD levels relative to vitamin D status and intervention.

This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine (IOM). An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes. The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health, consistent with a cause-and-effect relationship and providing a sound basis for determination of intake requirements. For extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements. Randomized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative. Based on bone health, Recommended Dietary Allowances (RDAs; covering requirements of ≥97.5% of the population) for calcium range from 700 to 1300 mg/d for life-stage groups at least 1 yr of age. For vitamin D, RDAs of 600 IU/d for ages 1–70 yr and 800 IU/d for ages 71 yr and older, corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/ml (50 nmol/liter), meet the requirements of at least 97.5% of the population. RDAs for vitamin D were derived based on conditions of minimal sun exposure due to wide variability in vitamin D synthesis from ultraviolet light and the risks of skin cancer. Higher values were not consistently associated with greater benefit, and for some outcomes U-shaped associations were observed, with risks at both low and high levels. The Committee concluded that the prevalence of vitamin D inadequacy in North America has been overestimated. Urgent research and clinical priorities were identified, including reassessment of laboratory ranges for 25-hydroxyvitamin D, to avoid problems of both undertreatment and overtreatment., There is an urgent clinical and public health need for consensus cut-points for serum 25OHD inadequacy to avoid problems of both under- and overtreatment.

Background Protein may have both beneficial and detrimental effects on bone health depending on a variety of factors, including protein source. Objective The aim was to conduct a systematic review and meta-analysis evaluating the effects of animal versus plant protein intake on bone mineral density (BMD), bone mineral content (BMC) and select bone biomarkers in healthy adults. Methods Searches across five databases were conducted through 10/31/16 for randomized controlled trials (RCTs) and prospective cohort studies in healthy adults that examined the effects of animal versus plant protein intake on 1) total body (TB), total hip (TH), lumbar spine (LS) or femoral neck (FN) BMD or TB BMC for at least one year, or 2) select bone formation and resorption biomarkers for at least six months. Strength of evidence (SOE) was assessed and random effect meta-analyses were performed. Results Seven RCTs examining animal vs. isoflavone-rich soy (Soy+) protein intake in 633 healthy peri-menopausal (n = 1) and post-menopausal (n = 6) women were included. Overall risk of bias was medium. Limited SOE suggests no significant difference between Soy+ vs. animal protein on LS, TH, FN and TB BMD, TB BMC, and bone turnover markers BSAP and NTX. Meta-analysis results showed on average, the differences between Soy+ and animal protein groups were close to zero and not significant for BMD outcomes (LS: n = 4, pooled net % change: 0.24%, 95% CI: -0.80%, 1.28%; TB: n = 3, -0.24%, 95% CI: -0.81%, 0.33%; FN: n = 3, 0.13%, 95% CI: -0.94%, 1.21%). All meta-analyses had no statistical heterogeneity. Conclusions These results do not support soy protein consumption as more advantageous than animal protein, or vice versa. Future studies are needed examining the effects of different protein sources in different populations on BMD, BMC, and fracture.

Vitamin D maintains calcium and phosphate homeostasis, is essential for bone development and maintenance, and also has non-skeletal effects [1]. Severe vitamin D deficiency causes rickets in children and osteomalacia in adults, while less severe vitamin D deficiency is associated with secondary hyperparathyroidism and increased bone turnover causing bone loss and fracture, especially in older populations [2]. Vitamin D deficiency has also been related to numerous diseases including diabetes and metabolic syndrome [3]. The obesity epidemic represents a public health concern worldwide and is associated with multiple comorbidities [4–7]. Vitamin D deficiency is also prevalent in many populations, including the obese [8–11]. Accumulating evidence shows that adiposity negatively influences vitamin D metabolism, storage, and action, and may influence the health risks associated with obesity. This chapter focuses on how obesity and body weight affect vitamin D metabolism and levels.

BACKGROUND Weight loss is associated with bone loss, but this has not been examined in overweight premenopausal women. OBJECTIVE The aim of this study was to assess whether overweight premenopausal women lose bone with moderate weight loss at recommended or higher than recommended calcium intakes. DESIGN Overweight premenopausal women [n = 44; x (+/-SD) age: 38 +/- 6.4 y; body mass index (BMI): 27.7 +/- 2.1 kg/m(2)] were randomly assigned to either a normal (1 g/d) or high (1.8 g/d) calcium intake during 6 mo of energy restriction [weight loss (WL) groups] or were recruited for weight maintenance at 1 g Ca/d intake. Regional bone mineral density and content were measured by dual-energy X-ray absorptiometry, and markers of bone turnover were measured before and after weight loss. True fractional calcium absorption (TFCA) was measured at baseline and during caloric restriction by using a dual-stable calcium isotope method. RESULTS The WL groups lost 7.2 +/- 3.3% of initial body weight. No significant decrease in BMD or rise in bone turnover was observed with weight loss at normal or high calcium intake. The group that consumed high calcium showed a strong relation (r = 0.71) between increased femoral neck bone mineral density and increased serum 25-hydroxyvitamin D. No significant effect of weight loss on TFCA was observed, and the total calcium absorbed was adequate at 238 +/- 81 and 310 +/- 91 mg/d for the normal- and high-calcium WL groups, respectively. CONCLUSION Overweight premenopausal women do not lose bone during weight loss at the recommended calcium intake, which may be explained by sufficient amounts of absorbed calcium.

A higher body weight has been shown to be protective against osteoporosis, while a low body weight is known to be associated with increased risk for fractures. The effects of obesity on bone quality are not clear, since there are reports suggesting that fracture risk in more obese individuals may be greater than expected. A review of how obesity may influence bone density and quality and fracture risk is discussed. Preliminary data is presented from our laboratory examining both obesity and menopause as independent factors on trabecular and cortical true volumetric bone mineral density (vBMD) using peripheral computerized tomography. We analyzed vBMD of the tibia in healthy women with a wide range of body weight (65–227 kg). We found that higher body mass index (BMI) may protect against trabecular bone loss after menopause, while cortical vBMD may be more sensitive to aging. We suggest that the tibia (a weight-bearing site) is sensitive to changes in body weight, and that aging and menopausal status have differential effects on vBMD. These results underscore the need to examine hormonal or nutritional regulators of bone quality as a goal for future studies, and could have important clinical implications for obese individuals who lose weight.