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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

To investigate Klotho level and its association with biochemical indices of primary hyperparathyroidism (PHPT). Fifty PHPT patients and fifty-two age- and body mass index-(BMI) matched healthy control subjects were recruited. In addition, twenty-five PHPT patients underwent parathyroidectomy (PTX) and had 4-month follow-up visits. Intact parathyroid hormone (iPTH), 25-hydroxyvitamin D [25(OH)D], calcium, albumin, corrected calcium, and Klotho levels were determined. There was no significant difference in age and BMI between PHPT subjects and controls (p > 0.05). PHPT patients had Klotho levels (15.4 ± 1.2 ng/mL) about 23% higher compared with those of the controls (11.9 ± 0.8 ng/mL), but this difference was not significant (p = 0.063). However, postmenopausal PHPT patients had 45% higher Klotho levels (17.6 ± 1.5 ng/ml) compared with postmenopausal controls (12.1 ± 0.9 ng/mL, p = 0.008). For postmenopausal subjects, Klotho levels had positive correlation with levels of iPTH (r = 0.25, p = 0.026) and corrected calcium (r = 0.34, p = 0.003), but negative correlation with 25(OH)D (r = −0.23, p = 0.042). After PTX, levels of iPTH and corrected calcium decreased and 25(OH)D levels increased to normal range (p

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.

In the mouse, the osteoblast-derived hormone Lipocalin-2 (LCN2) suppresses food intake and acts as a satiety signal. We show here that meal challenges increase serum LCN2 levels in persons with normal or overweight, but not in individuals with obesity. Postprandial LCN2 serum levels correlate inversely with hunger sensation in challenged subjects. We further show through brain PET scans of monkeys injected with radiolabeled recombinant human LCN2 (rh-LCN2) and autoradiography in baboon, macaque, and human brain sections, that LCN2 crosses the blood-brain barrier and localizes to the hypothalamus in primates. In addition, daily treatment of lean monkeys with rh-LCN2 decreases food intake by 21%, without overt side effects. These studies demonstrate the biology of LCN2 as a satiety factor and indicator and anorexigenic signal in primates. Failure to stimulate postprandial LCN2 in individuals with obesity may contribute to metabolic dysregulation, suggesting that LCN2 may be a novel target for obesity treatment., eLife digest Obesity has reached epidemic proportions worldwide and affects more than 40% of adults in the United States. People with obesity have a greater likelihood of developing type 2 diabetes, cardiovascular disease or chronic kidney disease. Changes in diet and exercise can be difficult to follow and result in minimal weight loss that is rarely sustained overtime. In fact, in people with obesity, weight loss can lower the metabolism leading to increased weight gain. New drugs may help some individuals achieve 5 to 10% weight loss but have side effects that prevent long-term use. Previous studies in mice show that a hormone called Lipocalin-2 (LCN2) suppresses appetite. It also reduces body weight and improves sugar metabolism in the animals. But whether this hormone has the same effects in humans or other primates is unclear. If it does, LCN2 might be a potential obesity treatment. Now, Petropoulou et al. show that LCN2 suppressed appetite in humans and monkeys. In human studies, LCN2 levels increased after a meal in individuals with normal weight or overweight, but not in individuals with obesity. Higher levels of LCN2 in a person’s blood were also associated with a feeling of reduced hunger. Using brain scans, Petropoulou et al. showed that LCN2 crossed the blood-brain barrier in monkeys and bound to the hypothalamus, the brain center regulating appetite and energy balance. LCN2 also bound to human and monkey hypothalamus tissue in laboratory experiments. When injected into monkeys, the hormone suppressed food intake and lowered body weight without toxic effects in short-term studies. The experiments lay the initial groundwork for testing whether LCN2 might be a useful treatment for obesity. More studies in animals will help scientists understand how LCN2 works, which patients might benefit, how it would be given to patients and for how long. Clinical trials would also be needed to verify whether it is an effective and safe treatment for obesity.

Persons with neurologically motor‐complete spinal cord injury (SCI) have a marked loss of bone mineral density (BMD) of the long bones of the lower extremities, predisposing them to fragility fractures, especially at the knee. Denosumab, a commercially available human monoclonal IgG antibody to receptor activator of nuclear factor‐κB ligand (RANKL), may provide an immunopharmacological solution to the rapid progressive deterioration of sublesional bone after SCI. Twenty‐six SCI participants with subacute motor‐complete SCI were randomized to receive either denosumab (60 mg) or placebo at baseline (BL), 6, and 12 months. Areal bone mineral density (aBMD) by dual energy x‐ray absorptiometry (DXA) at 18 months at the distal femur was the primary outcome and aBMD of the proximal tibia and hip were the secondary outcomes analyzed in 18 of the 26 participants (denosumab, n = 10 and placebo, n = 8). The metrics of peripheral QCT (pQCT) were the exploratory outcomes analyzed in a subsample of the cohort (denosumab, n = 7 and placebo n = 7). The mean aBMD (±95% CI) for the denosumab versus the placebo groups demonstrated a significant group × time interactions for the following regions of interest at BL and 18 months: distal femoral metaphysis = mean aBMD 1.187; 95% CI, 1.074 to 1.300 and mean aBMD 1.202; 95% CI, 1.074 to 1.329 versus mean aBMD 1.162; 95% CI, 0.962 to 1.362 and mean aBMD 0.961; 95% CI, 0.763 to 1.159, respectively (p

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.

The objective of this study was to determine the ability of either aerobic or resistance training to counter weight loss associated bone loss in older adults. 187 older adults (67 years, 70% women, 64% Caucasian) with obesity (body mass index: 34.5±3.7 kg/m2) and cardiovascular disease and/or metabolic syndrome were randomized to participate in an 18 month, community-based trial, with a follow-up assessment occurring at 30 months. Intervention arms included: weight loss alone (WL; 7–10% baseline weight), WL plus aerobic training (WL+AT), and WL plus resistance training (WL+RT). Dual energy x-ray absorptiometry (DXA) acquired total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD) and trabecular bone score (TBS); and biomarkers of bone turnover (Procollagen Type 1 N-Terminal Propeptide, C-Terminal Telopeptide of Type 1 Collagen) were measured at baseline, six, 18, and 30 (aBMD and TBS, only) months. Computed tomography (CT) acquired hip and spine volumetric BMD (vBMD), cortical thickness, and bone strength was measured in a subset at baseline (n=55) and 18 months. Total hip aBMD was reduced by 2% in all groups at 18 months, with primary analysis showing no significant treatment effects for any DXA, biomarker, or CT outcome. After adjustment for weight loss and followed to 30 months, secondary analyses reveal total hip [−0.018 (−0.023 to −0.012) g/cm2 vs −0.025 (−0.031 to −0.019) g/cm2; p=0.05] and femoral neck [−0.01 (−0.009 to 0.008) g/cm2 vs −0.011 (−0.020 to −0.002) g/cm2; p=0.06] aBMD estimates were modestly attenuated in WL+RT compared to WL. Additionally, lumbar spine aBMD was increased in WL [0.015 (0.007 to 0.024) g/cm2] and WL+RT [0.009 (0.000 to 0.017) g/cm2] compared to WL+AT [−0.003 (−0.012 to 0.005) g/cm2]; both p≤0.01. Community-based exercise does not prevent bone loss during active weight loss in older adults; however, adding resistance training may help minimize long-term hip bone loss. Trial Registration: clinicaltrials.gov Identifier:{"type":"clinical-trial","attrs":{"text":"NCT01547182","term_id":"NCT01547182"}}NCT01547182.

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.

In vivo studies measuring true fractional calcium (Ca) absorption have shown that dietary fat is a significant predictor of absorption and is influenced by luminal pH levels. However, whether changes in Ca bioaccessibility (CaB) can explain the effects on absorption has not been examined. In the current study, we examined two high fat diets enriched in either monounsaturated fatty acids or saturated fatty acids (SFA), and a low-fat diet (LFD), each with 50 mg Ca, and measured CaB at different intestinal regions during normal acidic or higher (pH = 7) gastrointestinal conditions using an in vitro gastrointestinal model. During normal pH conditions in the jejunum, there was an interaction between diet and time for CaB (P < 0.02), and CaB during the SFA diet was higher than LFD (P = 0.05). CaB was reduced by 90 ± 3% during higher compared with normal pH under all dietary conditions (P < 0.001). These findings indicate that fat intake, especially SFA enriched, is associated with a greater CaB in the jejunum, and may explain the higher Ca absorption in previous studies. In addition, the marked reduction in CaB under higher pH conditions could have implications in persons taking medications to reduce gastric acid.

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.

Background Despite evidence of the endocrine disrupting properties of zearalenone (ZEN) and alpha-zearalanol (zeranol, α-ZAL), they have been minimally studied in human populations. In previous cross-sectional analyses, we demonstrated that 9–10 years old girls with detectable urinary ZEN were of shorter stature and less likely to have reached the onset of breast development than girls with undetectable urinary ZEN. The aim of this study was to examine baseline concentrations of ZEN, (α-ZAL), and their phase-1 metabolites in relation to subsequent growth and timing of menarche using 10 years of longitudinal data. Methods Urine samples were collected from participants in the Jersey Girl Study at age 9–10 (n = 163). Unconjugated ZEN, (α-ZAL), and their metabolites were analyzed using high performance liquid chromatography and tandem mass spectrometry. Information on height, weight, and pubertal development was collected at a baseline visit with annual follow-up by mail thereafter. Cox regression was used to evaluate time to menarche in relation to baseline ZEN, (α-ZAL), and total mycoestrogen exposure. Z-scores for height and weight were used in mixed models to assess growth. Results Mycoestrogens were detectable in urine in 78.5% of the girls (median ZEN: 1.02 ng/ml, range 0–22.3). Girls with detectable urinary concentrations of (α-ZAL) and total mycoestrogens (sum of ZEN, (α-ZAL) and their metabolites) at baseline were significantly shorter at menarche than girls with levels below detection (p = 0.04). ZEN and total mycoestrogen concentrations were inversely associated with height- and weight-z-scores at menarche (adjusted β = − 0.18, 95% CI: -0.29, − 0.08, and adjusted β = − 0.10, 95% CI: -0.21, 0.01, respectively). Conclusion This study supports and extends our previous results suggesting that exposure to ZEN, (α-ZAL), and their metabolites is associated with slower growth and pubertal development in adolescent girls.

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.

The environmental estrogen, zearalenone (ZEA), is found in the food supply from Fusarium fungal contamination in grains and sometimes used as a growth promoter for beef cattle. Long-term exposure to ZEA and its metabolites may present health risk due to higher estrogenic activity. Serum ZEA metabolites were measured to determine the exposure and the association with food intake in 48 overweight/obese women (52 ± 9 years). The free and conjugated ZEA indicated the highest detection rate of all the metabolites. Conjugated ZEA and total ZEA metabolites were lower (p = 0.02) in overweight/obese than normal weight women, and free metabolites were either the same or showed a trend to be higher. In addition, those with highest (280-480 g/d) compared those with lowest (

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.

OBJECTIVES: Accumulating evidence suggests that assessing diet quality rather than nutrients in isolation provides a more accurate representation of the interactions between foods and diseases. The Healthy Eating Index (HEI) is a validated scoring system of diet quality focused on sufficiency of nutritional intake regarding the Dietary Guidelines for Americans wherein lower scores are associated with increased risk of several chronic diseases. The objective of the dietary intervention was to increase protein intake during weight loss in overweight/obese women, and examine dietary quality, as measured by the HEI. METHODS: Women (body mass index, BMI, 25–40 kg/m(2)) were randomly assigned to either high or normal protein groups during a one-year weight loss trial. Food diaries were collected at baseline and multiple times during the intervention. In this secondary outcome, HEI scores were assessed by entering food diary information into the National Cancer Institute's (NCI) Automated Self-Administered 24-hour (ASA24) Dietary Assessment Tool that configures data into 13 food components and calculates HEI in SAS v. 9.4. RESULTS: Forty-one women (58 ± 4.6 years of age with BMI, 32 ±4.5 kg/m(2)) had a baseline energy intake of 1831 ± 642 kilocalories; 47% of the energy consumed was from carbohydrates, 17% was from protein, and 36% was from fat. Also, HEI was 58.4 ± 15.3. Using standard HEI categories, 29% were in the poor diet quality range (80). CONCLUSIONS: Approximately 14% of American adults have poor diet quality (HEI

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)

Concern about the risk of bone loss in astronauts as a result of prolonged exposure to microgravity prompted the National Aeronautics and Space Administration to convene a Bone Summit with a panel of experts at the Johnson Space Center to review the medical data and research evidence from astronauts who have had prolonged exposure to spaceflight. Data were reviewed from 35 astronauts who had served on spaceflight missions lasting between 120 and 180 days with attention focused on astronauts who (1) were repeat fliers on long-duration missions, (2) were users of an advanced resistive exercise device (ARED), (3) were scanned by quantitative computed tomography (QCT) at the hip, (4) had hip bone strength estimated by finite element modeling, or (5) had lost >10% of areal bone mineral density (aBMD) at the hip or lumbar spine as measured by dual-energy X-ray absorptiometry (DXA). Because of the limitations of DXA in describing the effects of spaceflight on bone strength, the panel recommended that the U.S. space program use QCT and finite element modeling to further study the unique effects of spaceflight (and recovery) on bone health in order to better inform clinical decisions.

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.