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Bariatric surgery is an important weight loss tool in individuals with severe obesity. It is currently the most effective long-term weight loss treatment that lowers obesity-related comorbidities. It also has significant physiological and nutritional consequences that can result in gastrointestinal complications and micronutrient deficiencies. After gastric bypass, clinical events that negatively affect nutritional status include malabsorption, dumping syndrome, kidney stones, altered intestinal bile acid availability, bowel obstruction, ulcers, gastroesophageal reflux, and bacterial overgrowth. Risk factors for poor nutritional status and excessive loss of lean body mass and bone include reduced dietary quality and inadequate intake, altered nutrient absorption, and poor patient compliance with nutrient supplementation. There are unique concerns in adolescents, older individuals, and individuals who become pregnant postoperatively. With careful management, health-care professionals can assist with long-term weight loss success and minimize the risk of acute and long-term nutrition complications after bariatric surgery.
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Cirurgia Bariátrica , Humanos , Cirurgia Bariátrica/efeitos adversos , Estado Nutricional , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Feminino , Obesidade Mórbida/cirurgia , Redução de Peso , Gravidez , Fatores de Risco , Obesidade/cirurgiaRESUMO
CONTEXT: Primary hyperparathyroidism (PHPT) is accompanied by a decreased 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (DBP). High parathyroid hormone (PTH) is associated with elevated interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), yet the role of parathyroidectomy (PTX) on DBP and cytokines is not clear. OBJECTIVE: To prospectively evaluate the effect of PTX on inflammatory profiles, total and free 25OHD, and DBP in patients with PHPT. METHODS: Newly diagnosed patients with PHPT were recruited in the study (n=70). Twenty-eight patients returned after PTX, 3 months later. Biochemical markers were measured before and after PTX. A group of age and BMI-matched healthy subjects were included as controls (n=70). RESULTS: Prior to PTX, patients had lower serum DBP (37.5±6.0 vs 41.5±6.1mg/dL, p<0.001) and total 25OHD (30.1±9.5 vs 33.3±7.9ng/mL, P<0.05), but similar free 25OHD when compared to controls. Serum IL-6, C-reactive protein (CRP), and MCP-1 were higher in PHPT patients (p<0.05), whereas interleukin-10 (IL-10) was similar to controls. PTX increased total and free 25OHD and DBP (p<0.001), and decreased serum IL-6 and MCP-1 (p<0.05), but not CRP and IL-10. Multiple regression analysis indicated that the preoperative PTH explained a significant portion of the variance of IL-6 and MCP-1 (p<0.05). CONCLUSIONS: These findings suggest that PTH may upregulate the production of MCP-1 and IL-6 and downregulate circulating DBP in patients with PHPT, that are normalized by PTX. The exact effect of IL-6 and MCP-1 on DBP, vitamin D metabolites and the role on clinical outcomes in patients with PHPT is an area requiring further study.
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Twelve months following discontinuation of denosumab, the percent decrease in mean bone mineral density (BMD) values at the hip and knee regions were similar between both the denosumab and placebo groups. These findings emphasize the need for additional trials to understand the effect of continued administration of denosumab after subacute spinal cord injury (SCI) to avoid this demineralization. OBJECTIVE: To determine changes in BMD 1 year after denosumab was discontinued in participants with subacute SCI who had drug treatment initiated within 90 days post SCI and continued for 1 year. METHODS: Fourteen participants who completed a randomized, double-blinded, placebo-controlled drug trial (parent study: denosumab 60 mg (Prolia, Amgen Inc., n = 8) or placebo (n = 6); administered at baseline, 6, and 12 months) were followed 12 months after the 18 months from baseline primary end point was completed. The BMD of skeletal regions below the SCI at higher risk of fracture was measured [total hip, distal femur epiphysis (DFE), distal femur metaphysis (DFM), and proximal tibia epiphysis (PTE)] by dual energy X-ray absorptiometry. RESULTS: The percent decreases in mean BMD values at all regions of the hip and knee from 18 to 30 months were similar in both the denosumab and placebo groups. However, at 30 months, the absolute values for mean BMD remained significantly higher in the drug treatment than that of the placebo group at the DFM (p = 0.03), DFE (p = 0.04), and PTE (p = 0.05). CONCLUSIONS: In persons with SCI who initiated denosumab treatment during the subacute injury phase and maintained treatment for 1 year, the discontinuation of drug resulted in percent loss of mean BMD similar to that of the placebo group, with absolute mean BMD values at the knee regions at the 12-month follow-up visit significantly higher in the drug treatment than those in the placebo group. These data underscore the need to study continued administration of denosumab after subacute SCI to avoid marked demineralization in the sublesional skeleton upon discontinuation of this agent.
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Conservadores da Densidade Óssea , Doenças Ósseas Metabólicas , Traumatismos da Medula Espinal , Humanos , Denosumab/efeitos adversos , Densidade Óssea , Doenças Ósseas Metabólicas/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/farmacologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/tratamento farmacológico , Extremidade InferiorAssuntos
Dieta Baseada em Plantas , Ingestão de Energia , Recomendações Nutricionais , Humanos , Longevidade , Nutrientes/administração & dosagem , Literatura de Revisão como Assunto , Aminoácidos Essenciais/administração & dosagem , Fibras na Dieta , Proteínas de Vegetais Comestíveis/administração & dosagemRESUMO
Obesity is a risk factor for chronic diseases and moderate weight loss is generally recommended. Energy restriction results in the loss of hip bone mineral density (BMD) in older adults, but there is no consistent decline at the lumbar spine (LS), possibly due to vertebral abnormalities although this may also be dependent on the amount of weight loss. In this secondary analysis of weight loss trials investigating BMD and trabecular bone score (TBS) changes over 12-18 months, 92 postmenopausal women (60.8 ± 5.8 years; body mass index 32.7 ± 4.4 kg/m2) without osteoporosis, were divided into two groups: those who lost < 5% body weight (minimal) or ≥ 5% (moderate). Hip and LS-BMD and TBS were measured at baseline, 6 and 12-18 months. Exclusion of vertebral abnormalities (VE) was used to calculate BMD at the spine (LS-BMD-VE) using standard guidelines. Women lost 2.3 ± 2.4% and 8.5 ± 4.7% weight in the minimal and moderate weight loss groups, respectively. Over one third of the women had at least one vertebral abnormality or partially degraded TBS at baseline that worsened after weight loss, increasing to over 50% in this population (p < 0.05). TBS and hip BMD decreased with weight loss (p < 0.05), but LS-BMD did not decrease significantly. However, after excluding vertebral abnormalities, the LS-BMD-VE decreased in the entire population (p < 0.01), and by 1.7 ± 4.3% in the moderate weight loss group. This study suggests that older women without osteoporosis have vertebral abnormalities that obfuscated declines in BMD with weight loss, indicating that bone at the spine is further compromised.
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Osteoporose , Fraturas por Osteoporose , Absorciometria de Fóton/métodos , Idoso , Densidade Óssea , Osso Esponjoso , Feminino , Humanos , Vértebras Lombares , Obesidade/complicações , Sobrepeso , Redução de PesoRESUMO
PURPOSE OF REVIEW: There is strong evidence that poor dietary intake of certain micro- and macro-nutrients can negatively affect bone health. It is unclear if diet is the primary culprit for poor bone health in the vegan population. RECENT FINDINGS: Plant-based diets are gaining public interest since they may improve metabolic health. Studies that examine vegetarians and vegans together show a lower bone mineral density (BMD), but not always increased fracture risk compared to omnivores. However, vegans consistently have higher risk of fracture at multiple bone sites, especially at the hip. There is higher fracture risk in vegans which may be due to calcium and vitamin D intake, as well as amount of dietary protein and quality. Other nutrients (B vitamins, Se, Zn, Fe, iodine) or physiological factors (lower body mass index, microbiome, or endocrine profile) may also play a role but have not been examined and require further study.
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Dieta Vegetariana , Veganos , Humanos , Vegetarianos , Dieta Vegana , DietaRESUMO
Fruit and vegetables (F&V) have been a cornerstone of healthy dietary recommendations; the 2015-2020 U.S. Dietary Guidelines for Americans recommend that F&V constitute one-half of the plate at each meal. F&V include a diverse collection of plant foods that vary in their energy, nutrient, and dietary bioactive contents. F&V have potential health-promoting effects beyond providing basic nutrition needs in humans, including their role in reducing inflammation and their potential preventive effects on various chronic disease states leading to decreases in years lost due to premature mortality and years lived with disability/morbidity. Current global intakes of F&V are well below recommendations. Given the importance of F&V for health, public policies that promote dietary interventions to help increase F&V intake are warranted. This externally commissioned expert comprehensive narrative, umbrella review summarizes up-to-date clinical and observational evidence on current intakes of F&V, discusses the available evidence on the potential health benefits of F&V, and offers implementation strategies to help ensure that public health messaging is reflective of current science. This review demonstrates that F&V provide benefits beyond helping to achieve basic nutrient requirements in humans. The scientific evidence for providing public health recommendations to increase F&V consumption for prevention of disease is strong. Current evidence suggests that F&V have the strongest effects in relation to prevention of CVDs, noting a nonlinear threshold effect of 800 g per day (i.e., about 5 servings a day). A growing body of clinical evidence (mostly small RCTs) demonstrates effects of specific F&V on certain chronic disease states; however, more research on the role of individual F&V for specific disease prevention strategies is still needed in many areas. Data from the systematic reviews and mostly observational studies cited in this report also support intake of certain types of F&V, particularly cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries, which have superior effects on biomarkers, surrogate endpoints, and outcomes of chronic disease.
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Dieta Saudável , Frutas , Política Nutricional , Verduras , Ingestão de Alimentos , Humanos , Estudos Observacionais como Assunto , Revisões Sistemáticas como Assunto , Estados UnidosRESUMO
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<.05) but did not correlate with levels of total 25(OH)D (r = -0.14; 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.
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Hiperparatireoidismo Primário , Idoso , Calcifediol , Cálcio , Humanos , Pessoa de Meia-Idade , Hormônio Paratireóideo , Vitamina D/análogos & derivados , Deficiência de Vitamina DRESUMO
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 ß = - 0.18, 95% CI: -0.29, - 0.08, and adjusted ß = - 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.
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Disruptores Endócrinos/urina , Estrogênios/urina , Desenvolvimento Sexual , Zearalenona/urina , Zeranol/urina , Estatura , Peso Corporal , Criança , Monitoramento Ambiental , Feminino , Humanos , New JerseyRESUMO
OBJECTIVE: To evaluate free and bioavailable 25-hydroxyvitamin D (25[OH]D) levels in primary hyperparathyroidism (PHPT) patients. METHODS: 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. RESULTS: 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). CONCLUSION: 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. ABBREVIATIONS: 25(OH)D = 25-hydroxyvitamin D BMI = body mass index DBP = vitamin D-binding protein iPTH = intact parathyroid hormone PHPT = primary hyperparathyroidism.
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Hiperparatireoidismo Primário/sangue , Proteína de Ligação a Vitamina D/sangue , Vitamina D/análogos & derivados , Idoso , Disponibilidade Biológica , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radioimunoensaio , Vitamina D/sangue , Deficiência de Vitamina D/sangueRESUMO
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 NCT01892098.
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Desenvolvimento Ósseo/efeitos dos fármacos , Suplementos Nutricionais , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Puberdade/fisiologia , Zinco/administração & dosagem , Aminoácidos/urina , Biomarcadores/sangue , Peso Corporal , Desenvolvimento Ósseo/fisiologia , Remodelação Óssea/efeitos dos fármacos , Remodelação Óssea/fisiologia , Criança , Colágeno Tipo I/sangue , Feminino , Humanos , Fator de Crescimento Insulin-Like I/análise , Osteocalcina/sangue , Peptídeos/sangue , Placebos , Zinco/sangueRESUMO
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
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Estradiol/sangue , Pós-Menopausa/sangue , Pré-Menopausa/sangue , Proteína de Ligação a Vitamina D/sangue , Vitamina D/análogos & derivados , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Vitamina D/sangueRESUMO
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.
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Tecido Adiposo/cirurgia , Apoptose/fisiologia , Carcinoma de Células Escamosas/prevenção & controle , Ceratoacantoma/prevenção & controle , Lipectomia/métodos , Neoplasias Induzidas por Radiação/prevenção & controle , Raios Ultravioleta , Absorciometria de Fóton , Animais , Bromodesoxiuridina , Carcinoma de Células Escamosas/cirurgia , Caspase 3 , Dieta Hiperlipídica , Feminino , Imuno-Histoquímica , Ceratoacantoma/cirurgia , Camundongos , Neoplasias Induzidas por Radiação/cirurgia , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Endogenous estrogen has beneficial effects on mature bone and negatively affects the developing skeleton, whereas the effect of environmental estrogens is not known. Methoxychlor (MXC) is a synthetic estrogen known as a persistent organochlorine and used as a pesticide. Methoxychlor and its metabolites display estrogenic, anti-estrogenic and anti-androgenic activity and may therefore influence bone. Fifty-eight male fetal and neonatal rats were exposed to either: a negative control (DMSO), 0.020, 100 mg/kg MXC, or 1 mg/kg ß-estradiol-3-benzoate (EB; positive control). Rats were treated daily for 11 days, from embryonic day 19 to postnatal day (PND) 7 or for 4 days during the postnatal period (PND 0-7). All rats were analyzed at PND-84. Total body, femur, spine, and tibia areal bone mineral density (BMD) and content (BMC), lean body mass (LBM) and fat were measured by dual energy X-ray absorptiometry. Bone geometry and volumetric (v) BMD were measured using micro-computed tomography and biomechanical properties using three-point bending were assessed. Rats exposed to EB or MXC (at either the high and/or low dose), independent of exposure interval showed lower body weight, LBM, tibia and femur BMD and length, and total body BMD and BMC than DMSO control group (p ≤ 0.05). Methoxychlor and EB exposure increased cortical porosity compared to DMSO controls. Trabecular vBMD, number and separation, and cortical polar moment of inertia and cross-sectional area were lower due to EB exposure compared to control (p < 0.05). Early MXC exposure compromises cortical porosity and bone size at maturity, and could ultimately increase the risk of fracture with aging.
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Densidade Óssea/efeitos dos fármacos , Osso e Ossos/efeitos dos fármacos , Inseticidas/toxicidade , Metoxicloro/toxicidade , Efeitos Tardios da Exposição Pré-Natal/patologia , Absorciometria de Fóton , Animais , Animais Recém-Nascidos , Composição Corporal/efeitos dos fármacos , Feminino , Feto , Masculino , Gravidez , Ratos , Ratos Endogâmicos F344RESUMO
OBJECTIVE: To investigate the effects of parathyroidectomy on serum monocyte chemokine protein-1 (MCP-1) levels in patients with primary hyperparathyroidism (PHPT). METHODS: Forty-three PHPT patients, age 56 ± 12 years, underwent minimally invasive parathyroidectomy. Serum samples were collected at 0 and 15 to 20 minutes after parathyroid adenoma removal. Serum samples were stored at -70°C until time of assay. RESULTS: In 40 PHPT patients with a single adenoma, MCP-1 levels decreased from 342 ± 103 to 250 ± 77 pg/mL (P<.001) 15 to 20 minutes after parathyroid adenoma removal. MCP-1 levels were positively correlated with intact parathyroid hormone (PTH) levels (R = 0.47; P<.01). In 3 PHPT patients with double parathyroid adenoma, MCP-1 levels did not decrease after removal of the first adenoma but decreased 15 to 20 minutes after second adenoma removal. CONCLUSION: Our results provide evidence that the decrease in serum intact PTH due to minimally invasive parathyroidectomy results in an immediate decrease in serum MCP-1 levels.
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Fibroblast Growth Factor-23 (FGF23) is a bone secreted protein widely recognized as a critical regulator of skeletal and mineral metabolism. However, little is known about non-skeletal production of FGF23 and its role in tissues other than bone. Growing evidence indicates that circulating FGF23 levels rise with high fat diet (HFD) and they are positively correlated with body mass index (BMI) in humans. In the present study, we show for the first time that increased circulating FGF23 levels in obese humans correlate with increased expression of adipose Fgf23 and both positively correlate with BMI. To understand the role of adipose-derived Fgf23, we generated adipocyte-specific Fgf23 knockout mice (AdipoqFgf23Δfl/Δfl) using the Adiponectin (Adipoq)-Cre driver, which targets mature white, beige, and brown adipocytes. Our data show that targeted ablation of Fgf23 in adipocytes prevents HFD-fed female mice from gaining body weight and fat mass while preserving lean mass, but has no effect on male mice, indicating the presence of sexual dimorphism. These effects are observed in the absence of changes in food and energy intake. Adipose Fgf23 inactivation also prevents dyslipidemia, hyperglycemia, and hepatic steatosis in female mice. Moreover, these changes are associated with decreased respiratory exchange ratio (RER) and increased brown fat Ucp1 expression in KO mice compared to HFD-fed control mice (Fgf23fl/fl). In conclusion, this is the first study highlighting that targeted inactivation of Fgf23 is a promising therapeutic strategy for weight loss and lean mass preservation in humans.
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Excess body weight due to obesity has traditionally been considered to have a positive effect on bone; however, more recent findings suggest that bone quality is compromised. Both obesity and caloric restriction increase fracture risk and are regulated by endocrine factors and cytokines that have direct and indirect effects on bone and calcium absorption. Weight reduction will decrease bone mass and mineral density, but this varies by the individual's age, gender, and adiposity. Dietary modifications, exercise, and medications have been shown to attenuate the bone loss associated with weight reduction. Future obesity and weight loss trials would benefit from assessment of key hormones, adipokine and gut peptides that regulate calcium absorption, and bone mineral density and quality by using sensitive techniques in high-risk populations.