Publications by authors named "Flávia F Bezerra"

16 Publications

  • Page 1 of 1

Reproducibility and Validity of Capillary Dried Blood Spot for Diagnosis of Vitamin A Deficiency and Anemia in Children <5 Years Old.

J Nutr 2021 Jul 22. Epub 2021 Jul 22.

Department of Social Nutrition, Nutrition Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil.

Background: Vitamin A deficiency (VAD) and anemia are the most prevalent nutritional deficiency in children globally. The dried blood spot (DBS) method has been used in prevalence studies of VAD and anemia in different age groups. However, it has not yet been validated for children.

Objectives: This study aimed to assess the reproducibility and validity of DBS in the diagnosis of VAD and anemia in preschoolers.

Methods: Venous and capillary blood samples were collected from a representative sample of children <5 y old who attended the public health system in Rio de Janeiro. Serum retinol and hemoglobin were measured in 235 and 182 children, respectively. Serum retinol was measured with HPLC and hemoglobin was measured with spectrophotometry in samples of venous (gold standard) and capillary blood (test method, DBS). DBS reproducibility was assessed with the intraclass correlation coefficient (ICC), κ, and prevalence-adjusted and bias-adjusted κ (PABAK). DBS validity was assessed with sensitivity, specificity, accuracy index (AI), positive predictive value (PPV), and negative predictive value (NPV).

Results: DBS showed very good reproducibility for serum retinol (ICC = 0.94, κ = 0.83, PABAK = 0.76) and very good/good reproducibility for hemoglobin (ICC = 0.86, κ = 0.69, PABAK = 0.69). Prevalence rates for VAD by the reference and test methods were 11.5% and 11.9%, respectively, whereas the anemia rates were 19.2% and 46.2%. The test method showed low sensitivity (33%) and PPV (32%) and high specificity (91%) and NPV (92%) for serum retinol. For hemoglobin, the test method showed fair sensitivity (71%), low PPV (30%), fair specificity (60%), and high NPV (90%). AI was 83% for VAD and 62% for anemia.

Conclusions: The results suggest that DBS is adequate for the diagnosis of VAD in preschool children, but not for anemia.
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http://dx.doi.org/10.1093/jn/nxab226DOI Listing
July 2021

Reduction in Bone Loss from 5 to 20 Weeks Postpartum in Adolescents Supplemented with Calcium Plus Vitamin D during Pregnancy Is Not Sustained at 1 Year Postpartum: Follow-up Study of a Randomized Controlled Trial.

J Nutr 2021 03;151(3):548-555

School of Nutrition, University of the Republic, Montevideo, Uruguay.

Background: Calcium plus vitamin D supplementation of pregnant Brazilian adolescents with habitually low calcium intake (∼600 mg/d) reduced bone loss during the first 20 wk postpartum.

Objective: We investigated maternal bone mass changes during the first year postpartum as a follow-up of the clinical trial.

Methods: Pregnant adolescents (14-19 y) received calcium (600 mg/d) plus cholecalciferol (200 IU/d) supplementation (n = 30) or placebo (n = 26) from 26 wk of gestation until parturition. Bone area and bone mineral content and bone mineral density (BMD) at total body, lumbar spine, and hip (total and femoral neck) were assessed by DXA at 3 time points postpartum (5 wk, 20 wk, and 56 wk). Intervention group, time postpartum, and group × time interaction effects were tested by repeated-measures mixed-effects models adjusting for calcium intake, return of menses, breastfeeding practices, and body weight.

Results: Time (P < 0.05) but not group affected several absolute bone measurements. There was a group × time interaction for femoral neck BMD (P = 0.045). Mean ± SE values (g/cm2) at 5 wk, 20 wk, and 56 wk were, respectively, 1.025 ± 0.026, 0.980 ± 0.026, and 1.022 ± 0.027 for the placebo group and 1.057 ± 0.025, 1.030 ± 0.024, and 1.055 ± 0.025 for the supplemented group. An interaction also was observed for percentage change in femoral neck BMD relative to 5 wk (P = 0.049), with a more pronounced decrease in the placebo group (-4.58 ± 0.42%) than in the supplemented group (-3.15% ± 0.42%) at 20 wk (P = 0.019), and no difference between groups at 56 wk (-0.44% ± 0.71% in the placebo and -0.76% ± 0.62% in the supplemented group; P = 0.65).

Conclusions: Calcium plus vitamin D supplementation of the adolescent mothers reduces the magnitude of bone loss at the femoral neck from 5 to 20 wk postpartum without an effect on bone changes after 1 y postpartum, indicating that there is no sustained effect of the supplement tested.
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http://dx.doi.org/10.1093/jn/nxaa418DOI Listing
March 2021

Association of Visceral and Subcutaneous Fat Mass With Bone Density and Vertebral Fractures in Women With Severe Obesity.

J Clin Densitom 2021 Jul-Sep;24(3):397-405. Epub 2020 Oct 16.

Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

Introduction: The aim of this study was to evaluate the association of visceral and subcutaneous adipose tissue with bone mineral density (BMD), geometric indices of femoral neck strength and vertebral fractures in pre- and postmenopausal women with severe obesity.

Methods: A cross-sectional study was conducted with pre- (n = 37) and postmenopausal (n = 21) women with body mass index higher than 40 kg/cm. BMD at total body, lumbar spine, hip and forearm, presence of vertebral fractures, lean mass, visceral, and subcutaneous adipose tissue were assessed by DXA. Geometric indices of femoral neck strength were calculated by DXA. Serum bone turnover markers (CTX and osteocalcin) and 25(OH)D were also measured.

Results: BMD at all studied sites was similar in pre- and postmenopausal women. In postmenopausal women, total subcutaneous adipose tissue was inversely associated with BMD at total femur (β = -0.009; 95% confidence interval [CI] -0.017; -0.002) and with strength index (β = -0.03; 95% CI -0.04; -0.01). In premenopausal women, visceral adipose tissue was inversely associated with cross-sectional moment of inertia (β = -0.95; 95%CI -1.89; -0.01). Vertebral fractures were highly prevalent in premenopausal (32%), and even more frequent among postmenopausal women (55%).

Conclusion: Taken together, our results suggest that both visceral and subcutaneous fat may be detrimental for bone health in pre- and postmenopausal women, and that severe obesity may increase the risk of vertebral fractures, even in young women.
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http://dx.doi.org/10.1016/j.jocd.2020.10.005DOI Listing
October 2020

Free and Bioavailable Fractions of Vitamin D: Association with Maternal Characteristics in Brazilian Pregnant Women.

J Nutr Metab 2020 16;2020:1408659. Epub 2020 Sep 16.

Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

Normal pregnancy is characterized by many changes in vitamin D metabolism, challenging the assessment of vitamin D status based exclusively on serum total 25-hydroxyvitamin D (25(OH)D). We hypothesized that measuring free and bioavailable fractions contributes to a better vitamin D status assessment in late pregnancy. Our aim was to evaluate a broad set of biomarkers of vitamin D status in Brazilian women in the third trimester of pregnancy. This cross-sectional study was conducted in women ( = 123, 18-44 y, 27-41 wk gestation) attended in a public maternity in Rio de Janeiro (2016-2018). Biomarkers included serum concentrations of total 25(OH)D, parathyroid hormone (PTH), vitamin D-binding protein (DBP), and free and bioavailable fractions of 25(OH)D. Vitamin D insufficiency (<50 nmol/L) was prevalent in 47.9% of the pregnant women. Serum 25(OH)D was inversely associated with the gestational week ( = -0.71, 95% confidence interval (CI): -1.31 to -0.16) and season, being lower in autumn ( = -9.90, 95% CI: -16.14 to -3.64) and winter ( = -16.74, 95%CI: -23.13 to -10.34). Concentrations of DBP, and free and bioavailable 25(OH)D were also inversely associated with winter months ( < 0.05). DBP was directly associated with prepregnancy BMI ( = 5.84, 95% CI: 0.62 to 11.06). The recognized season-effect on total 25(OH)D appeared to also occur on free and bioavailable fractions. Although advanced gestational age was associated with lower total 25(OH)D, our results suggest an adaptive mechanism responsible for maintaining free fraction during the 3 trimester. We also suggest that starting pregnancy in obese condition may have an impact on vitamin D bioavailability, which deserves further investigation.
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http://dx.doi.org/10.1155/2020/1408659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519195PMC
September 2020

Obesity, dynapenia, and their combination: Implications for bone mineral density in Brazilian adults-the Pró-Saúde study.

Nutrition 2021 01 20;81:110898. Epub 2020 Jun 20.

Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

Objectives: This study aimed to evaluate bone mineral density (BMD) in the presence or absence of dynapenia or obesity in Brazilian adults.

Methods: This is a cross-sectional study conducted in 502 adults (age: 33-81 y; 51% women) participating in the Pró-Saúde study, a cohort of civil servants at the university campuses in Rio de Janeiro, Brazil. Body composition and BMD were determined by dual energy x-ray absorptiometry. Handgrip strength was measured using a dynamometer. According to measures of handgrip strength (≤19 kg for women; ≤32 kg for men) and fat mass (>30% for men; >40% for women), participants were classified into four groups: non-obese non-dynapenic, obese non-dynapenic, non-obese dynapenic, and obese dynapenic. The association between BMD at each specific bone site and obesity, dynapenia, and their interaction was evaluated using a general linear model.

Results: The prevalence of dynapenic obesity was 14% in men and 15.2% in women. Dynapenia alone was not associated with BMD at any site in either men nor women. Obesity and dynapenia interacted to influence BMD in women (P < 0.05). Total body, lumbar spine, and femoral neck BMD were higher by 6.3%, 9.3%, and 10.4%, respectively, in dynapenic obese women compared with their non-obese counterparts (P < 0.05). In men, obesity, dynapenia, and their combination were not associated with BMD at any site.

Conclusions: Our results suggest that dynapenia, obesity, and their combination may affect BMD in a sex-dependent manner. In the presence of dynapenia, fat mass appears to exert a protective effect on BMD in women, but not in men.
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http://dx.doi.org/10.1016/j.nut.2020.110898DOI Listing
January 2021

Variants in gene encoding for vitamin D binding protein were associated with leukocyte telomere length: The Pró-Saúde Study.

Nutrition 2020 03 25;71:110618. Epub 2019 Oct 25.

Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.

Objective: The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in vitamin D metabolic pathway genes, serum 25-hydroxyvitamin D [25(OH)D] concentrations, and leukocyte telomere length (LTL) in Brazilian adults.

Methods: The study population comprised 461 participants (33-79 y of age; 51% women) from the Pró-Saúde Study, a cohort of civil servants at a university campus in Rio de Janeiro, Brazil. LTL, genotypes of vitamin D-related SNPs (rs12785878, rs10741657, rs6013897, and rs2282679), and serum 25(OH)D concentrations were determined cross-sectionally. Differences in age- and sex-adjusted LTL means by categories of genotypes and 25(OH)D serum concentrations were evaluated. LTL associations with genotypes and 25(OH)D were investigated using multiple linear regression models adjusted for sociodemographic characteristics and markers of health behavior.

Results: Participants with CC genotype (rs2282679) had shorter age- and sex-adjusted mean LTL than those with AC and AA genotypes (mean ± SE: 0.51 ± 0.03, 0.58 ± 0.01 and 0.5 ± 0.01, respectively, P < 0.05). In adjusted analyses, the CC genotype (rs2282679) was inversely associated with LTL (β = -0.061; 95% confidence interval, -0.120 to -0.001). Other vitamin D-related SNPs and serum 25(OH)D concentrations were not associated with LTL.

Conclusions: Genetic variations in the gene encoding vitamin D binding protein (GC - rs2282679) were associated with LTL, suggesting an influence of vitamin D status on telomere length that may start early in life.
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http://dx.doi.org/10.1016/j.nut.2019.110618DOI Listing
March 2020

Nutritional Status, Nutrient Intake, and Food Diversity Among Children With Sickle Cell Anemia.

J Pediatr Hematol Oncol 2019 04;41(3):e141-e145

Reference Center for Nutrition of Persons with Sickle Cell Disease (NUTRIFAL), Rio de Janeiro, Brazil.

Children with sickle cell anemia (SCA) often exhibit nutritional deficiencies and are at high risk of dying before the age of 5 years. Ensuring adequate nutrition is a critical part of health care for such children. This study aimed to investigate the association between nutritional status, nutrient intake, and food diversity in children with SCA. A descriptive cross-sectional study was conducted on 74 children with SCA, between 24 and 71 months of age. Anthropometric measurements, food and nutrients consumption were determined. The prevalence of low weight, stunting, and overweight/obesity were 16.2%, 35.1%, and 16.2%, respectively. Mean folic acid intake was low (49.05%±51.22%), whereas the intakes of protein (426.71%±171.93%), retinol (292.97%±403.88%), phosphorus (204.55%±151.35%), magnesium (233.02%±151.14%), iron (250.76%±165.81%), and zinc (243.21%±148.40%) were high. The dietary phosphorus/protein ratio was high for 31.1% of the children, and 44.6% of the children had low dietary diversity score. No correlation was found between food diversity, nutrient adequacy, and nutritional status. Despite the adequacy of the intake of most micronutrients, diet quality was inadequate, constituting mainly ultraprocessed foods. Knowing the food consumption pattern of these children enables a more resolute nutritional intervention.
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http://dx.doi.org/10.1097/MPH.0000000000001377DOI Listing
April 2019

Activation of Nrf2-Antioxidant Signaling by 1,25-Dihydroxycholecalciferol Prevents Leptin-Induced Oxidative Stress and Inflammation in Human Endothelial Cells.

J Nutr 2017 04 1;147(4):506-513. Epub 2017 Mar 1.

Departments of Basic and Experimental Nutrition and

Obesity is associated with hyperleptinemia and endothelial dysfunction. Hyperleptinemia has been reported to induce both oxidative stress and inflammation by increasing reactive oxygen species production. The objective of this study was to determine the effects of 1,25-dihydroxycholecalciferol [1,25(OH)D] against leptin-induced oxidative stress and inflammation in human endothelial cells. Small interfering RNA (siRNA) were used to knock down the expression of vitamin D receptor (VDR) in human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated for 4 h with physiologic (10 M) or supraphysiologic (10 M) concentrations of 1,25(OH)D and exposed to leptin (10 ng/mL). Superoxide anion production and translocation of nuclear factor (erythroid-derived 2)-like 2 (NRF2) and nuclear transcription factor κB (NF-κB) subunit p65 to the nucleus and the activation of their target genes were quantified. Pretreatment of HUVECs with 1,25(OH)D prevented the leptin-induced increase in superoxide anion production ( < 0.05). Pretreatment with 1,25(OH)D further increased NRF2 translocation to the nucleus (by 3-fold; < 0.05) and increased mRNA expression of superoxide dismutase 2 (; by 2-fold), glutathione peroxidase (; by 3-fold), NAD(P)H dehydrogenase (quinone) 1 (; by 4-fold), and heme oxygenase 1 (; by 2-fold) ( < 0.05). Leptin doubled the translocation of NF-κB ( < 0.05) to the nucleus and increased ( < 0.05) the upregulation of vascular inflammatory mediators such as monocyte chemoattractant protein 1 (; by 1-fold), transforming growth factor β ( β by 1-fold), and vascular cell adhesion molecule 1 (; by 4-fold) ( < 0.05), which were prevented ( < 0.05) by pretreatment with 1,25(OH)D Protective effects of 1,25(OH)D were confirmed to be VDR dependent by using VDR siRNA. Pretreatment with 1,25(OH)D in the presence of a high concentration of leptin has a beneficial effect on HUVECs through the regulation of mediators of antioxidant activity and inflammation.
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http://dx.doi.org/10.3945/jn.116.239475DOI Listing
April 2017

Association between fat mass and bone mineral density among Brazilian women differs by menopausal status: The Pró-Saúde Study.

Nutrition 2017 Jan 24;33:14-19. Epub 2016 Aug 24.

Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

Objective: The aim of this study was to investigate the association between bone mineral density (BMD) and fat mass (FM) in a multiethnic population of Brazilian women and to evaluate the influence of total body mass and lean mass on this association.

Methods: This was a cross-sectional study nested within the Pro-Saúde Study, a prospective cohort of university civil servants in Rio de Janeiro. Participants were pre- (n = 100) and postmenopausal (n = 166) women. Total fat, lean mass, and BMD of total body, lumbar spine, and femoral neck were measured using dual energy x-ray absorptiometry. The association of BMD with FM was investigated after adjustment for total body mass (model 1) and lean mass (model 2) and potential confounding variables using multivariate linear regression models.

Results: In model 1, FM was inversely associated with BMD for total body (B = -0.010; P < 0.01) and for femoral neck (B = -0.009 P < 0.05) in premenopausal women. No association between FM and BMD was observed in postmenopausal women. Model 2 yielded direct associations between FM and BMD (total and specific sites; B = 0.003-0.008; P < 0.01) in postmenopausal women only.

Conclusions: Independently of the adjustment used, the results of the present study suggest the absence of an inverse association between FM and BMD in postmenopausal women. Additionally, when adjusted for lean mass, a direct association between FM and bone mass can be observed, suggesting that for postmenopausal women being slightly obese does not confer excessive risk for bone loss and may even result in a bone density advantage.
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http://dx.doi.org/10.1016/j.nut.2016.08.001DOI Listing
January 2017

Calcium plus vitamin D supplementation during pregnancy interacts with polymorphisms in the promoter region of the VDR gene to affect postpartum bone mass of Brazilian adolescent mothers: A randomized controlled trial.

Nutrition 2016 Oct 16;32(10):1068-74. Epub 2016 Mar 16.

Instituto de Nutrição, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address:

Objective: We investigated whether calcium plus vitamin D supplementation interacts with polymorphisms in the VDR gene promoter region to affect changes on maternal bone mass from 5 to 20 wk postpartum in Brazilian adolescent mothers.

Methods: Pregnant adolescents (14-19 y) randomly received calcium plus cholecalciferol (600 mg/d + 200 IU/d, n = 30) or placebo (n = 26) from 26 wk of pregnancy until parturition. Bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at total body, lumbar spine, total hip, and femoral neck were evaluated at 5 and 20 wk postpartum. Serum 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone concentrations were measured. Real-time polymerase chain reaction was used for genotyping rs7139166 (1521 pb G > C) and rs4516035 (1012 pb A > G). Interactions between supplementation and polymorphisms were adjusted for significant covariates.

Results: Changes in serum 25(OH)D from pregnancy to postpartum differed between supplemented and placebo groups for mothers carrying 1521 GG/1012 AA genotypes (P = 0.004). Only in the placebo group, mothers carrying 1521 GG/1012 AA had greater reduction in total BMD z score, femoral neck BMC, and BMD from 5 to 20 wk postpartum compared with those with 1521 GC/1012 AG (P < 0.05). In the placebo group, total hip BA decreased from 5 to 20 wk postpartum in adolescents with 1521 GG/1012 AA, but increased in those with 1521 GC/1012 AG (P < 0.05), in contrast to the supplemented group.

Conclusion: Calcium plus vitamin D supplementation during pregnancy interacted with polymorphisms in the VDR gene promoter region affecting postpartum bone loss. The increased supply of calcium and vitamin D appeared to minimize postpartum bone loss particularly in adolescents with 1521 GG/1012 AA.
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http://dx.doi.org/10.1016/j.nut.2016.03.002DOI Listing
October 2016

Calcium Plus Vitamin D Supplementation During the Third Trimester of Pregnancy in Adolescents Accustomed to Low Calcium Diets Does Not Affect Infant Bone Mass at Early Lactation in a Randomized Controlled Trial.

J Nutr 2015 Jul 27;145(7):1515-23. Epub 2015 May 27.

Food and Nutritional Biochemistry Laboratory, Chemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; School of Nutrition, University of the Republic, Montevideo, Uruguay

Background: Pregnancy and lactation in adolescents with low calcium intake may impair fetal growth and infant bone mass.

Objective: We investigated the effects of calcium plus vitamin D supplementation during pregnancy in Brazilian adolescent mothers consuming low calcium diets (∼600 mg/d) on fetal biometry and infant bone mass, and the relation between infant and maternal bone mass during early lactation.

Methods: Infants of mothers who received calcium (600 mg/d) plus cholecalciferol (200 IU/d) supplementation (n = 30) or placebo (n = 26) from 26 wk of gestation until parturition were studied. Fetal biometric measurements at 23 and 36 wk of gestation were obtained from medical records. Infant anthropometric and total body bone measurements [bone mineral content (BMC), bone area (BA), and bone mineral density (BMD)] at 5 wk postpartum were assessed by dual-energy X-ray absorptiometry. Maternal BMD z scores for total body, lumbar spine, total hip, and femoral neck at 5 wk postpartum were obtained. Group comparisons were adjusted for significant covariates.

Results: Maternal mean serum 25-hydroxyvitamin D was 59 nmol/L at baseline in both groups. No differences in fetal measurements at 36 wk of gestation were observed between the groups, except for body weight and its increment from 23 to 36 wk, which were higher in the supplemented group (6.8%, P = 0.014 and 10.5%, P = 0.07, respectively). Infant BMC (61.1 ± 21.7 g), BA (167 ± 79 cm(2)), and BMD (0.385 ± 0.069 g/cm(2)) did not significantly differ between the groups. In the placebo group, infant BMC and BA were negatively correlated with maternal BMD z scores for total body (r = -0.40 and r = -0.47; P < 0.05) and hip (r = -0.41 and r = -0.46; P < 0.05). In contrast, no correlations were observed in the supplemented group.

Conclusions: Calcium and vitamin D supplementation of the adolescents studied resulted in higher fetal body weight at 36 wk of gestation and had no effect on infant bone mass at 5 wk postpartum. Because correlations between maternal and infant bone mass were evident only in the placebo group, infant bone mass appeared to be more dependent on maternal skeletal mass when calcium intake was low. This trial was registered at clinicaltrials.gov as NCT01732328.
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http://dx.doi.org/10.3945/jn.114.208140DOI Listing
July 2015

Physical exercise is associated with better fat mass distribution and lower insulin resistance in spinal cord injured individuals.

J Spinal Cord Med 2014 Jan 26;37(1):79-84. Epub 2013 Nov 26.

Objectives: The aim of the study was to compare total and regional body composition and their relationship with glucose homeostasis in physically active and non-active individuals with cervical spinal cord injury (c-SCI).

Methods: Individuals with lesion level between C5-C7 were divided into two groups: physically active (PA; n = 14; who practiced physical exercise for at least 3 months, three times per week or more, minimum of 150 minutes/week): and non-physically active (N-PA n = 8). Total fat mass (t-FM) and regional fat mass (r-FM) were assessed by dual energy X-ray absorptiometry. Fasting plasma insulin (FPI) was determined by enzyme-linked immunosorbent assay.

Results: PA group present lower (P < 0.01) total fat mass (t-FM), % and kg, regional fat mass (r-FM), % and kg, FPI levels and HOMA index, while they had higher (P < 0.001) total free fat mass (t-FFM), %, and regional free fat mass (r-FFM), %, compared to the N-PA group. In the N-PA group, FPI and HOMA index were negatively (P < 0.05) correlated with FFM% (r = -0.71, -0.69, respectively) and positively correlated to trunk-FM (r = 0.71, 0.69, respectively) and trunk-FM:t-FM (kg) ratio (r = 0.83, 0.79, respectively).

Conclusion: Physical exercise is associated with lower t-FM, r-FM, and insulin resistance, which could contribute to the decrease of the risk of cardiovascular and metabolic conditions in individuals with c-SCI.
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http://dx.doi.org/10.1179/2045772313Y.0000000147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066554PMC
January 2014

Effect of calcium plus vitamin D supplementation during pregnancy in Brazilian adolescent mothers: a randomized, placebo-controlled trial.

Am J Clin Nutr 2013 Jul 29;98(1):82-91. Epub 2013 May 29.

Laboratório de Bioquímica Nutricional e de Alimentos, Instituto de Química and the Maternidade Escola, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Background: Pregnancy and lactation in adolescents with habitually low calcium intake may adversely affect maternal bone mass.

Objective: We investigated the effect of calcium plus vitamin D supplementation during pregnancy on bone mass during lactation in Brazilian adolescent mothers with low-calcium diets (∼600 mg/d).

Design: Pregnant adolescents (14-19 y) randomly received daily calcium (600 mg) plus vitamin D3 (200 IU) (n = 30) or a placebo (n = 26) from 26 wk of pregnancy (baseline) until parturition. The bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at the total body, lumbar spine, and hip (total and femoral neck) were evaluated by using dual-energy X-ray absorptiometry at 5 and 20 wk postpartum. Serum hormones and 25-hydroxyvitamin D [25(OH)D] were measured. Group comparisons were adjusted for significant covariates.

Results: The mean serum 25(OH)D concentration was 59 nmol/L at baseline. In comparison with the placebo, 25(OH)D tended to be 14-15 nmol/L higher postpartum in the supplemented group (P = 0.08). Total body and hip BMC and BMD decreased over time (P ≤ 0.005) in both groups with a group × time interaction at the femoral neck (P < 0.04). Supplemented mothers had higher lumbar spine BA (6.7%; P = 0.002) and lumbar spine BMC (7.9%, P = 0.08) than did mothers who consumed the placebo at 5 wk postpartum. At 20 wk postpartum, differences between groups were more evident, with higher lumbar spine BMC (13.9%), lumbar spine BA (6.2%), and lumbar spine BMD (10.6%) in the supplemented group (P ≤ 0.008).

Conclusions: Calcium plus vitamin D supplementation during pregnancy of adolescents with low calcium intake results in higher lumbar spine bone mass and a reduced rate of femoral neck bone loss during lactation. Additional studies are required to determine whether bone effects are temporary or long-lasting. This trial was registered at clinicaltrials.gov as NCT01732328.
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http://dx.doi.org/10.3945/ajcn.112.056275DOI Listing
July 2013

Bone mass and breast milk calcium concentration are associated with vitamin D receptor gene polymorphisms in adolescent mothers.

J Nutr 2008 Feb;138(2):277-81

Laboratório de Bioquímica Nutricional e de Alimentos, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 21941-909.

Lactation-associated bone loss has been reported in adolescent mothers. Polymorphisms in the vitamin D receptor (VDR) gene may contribute to differences in the physiologic skeletal response to lactation in these mothers. We evaluated the influence of VDR gene polymorphisms ApaI, BsmI, and TaqI on bone mass, bone and calcium-related hormones, and breast milk calcium of lactating adolescents with habitually low calcium intake. Total body bone mineral content (TBMC), total body bone mineral density (TBMD), lumbar spine BMD (LSBMD), serum hormones [intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, insulin-like growth factor-I (IGF1), prolactin, and estradiol), and breast milk calcium were measured in 40 lactating Brazilian adolescents (15-18 y), and compared by VDR genotype subgroups after adjustment for calcium intake and postmenarcheal and lactational periods. TBMD and LSBMD Z scores were -0.55 +/- 1.01 and -1.15 +/- 1.48, respectively. LSBMD was higher (21%; P < 0.05) in adolescents with the aa genotype (n = 5) compared with those with the AA genotype (n = 7). TBMC and IGF1 were higher (23 and 50%, respectively; P < 0.05) in adolescents with tt (n = 4) than those with TT (n = 29) and Tt (n = 7) genotypes. Breast milk calcium and serum iPTH were higher (24 and 80%, respectively; P < 0.05) in adolescents with bb (n = 8) compared with those with BB (n = 21) genotype. These results indicate that bone mass and breast milk calcium are significantly associated with VDR genotypes in lactating Brazilian adolescents. Those with aa and tt genotypes had a better bone status and those with bb genotype had greater breast milk calcium.
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http://dx.doi.org/10.1093/jn/138.2.277DOI Listing
February 2008

Bone mass is recovered from lactation to postweaning in adolescent mothers with low calcium intakes.

Am J Clin Nutr 2004 Nov;80(5):1322-6

Laboratório de Bioquímica Nutricional e de Alimentos, Instituto de Química, Universidade Federal do Rio de Janeiro, Brazil.

Background: Adolescent mothers may be at increased risk of irreversible bone loss during pregnancy and lactation, particularly when calcium intake is low.

Objective: Longitudinal changes in bone mass from lactation to postweaning were evaluated in 10 adolescent mothers aged 15-18 y who habitually consumed <500 mg Ca/d.

Design: Total-body bone mineral content (TBBMC), total-body bone mineral density (TBBMD), and lumbar spine bone mineral density (LSBMD) were measured at lactation (6-24 wk postpartum) and after weaning (12-30 mo postpartum). Serum hormones (intact parathyroid hormone, estradiol, and prolactin), serum calcium, and markers of bone turnover [urinary N-telopeptide cross-linking region of type I collagen (NTx) and plasma activity of bone alkaline phosphatase] were measured at lactation.

Results: TBBMC, total calcium content, TBBMD, and LSBMD increased from lactation to postweaning (P < 0.01). TBBMD and LSBMD were, respectively, 3.6% and 9.7% lower than predicted at lactation and 0.3% and 4.8% lower than predicted in the postweaning period. The increase in age-matched TBBMD adequacy was correlated with the time after resumption of menses (r = 0.86, P < 0.01). Calcium accretion from lactation to postweaning correlated negatively with estradiol (r = -0.86) and prolactin (r = -0.69) and positively with intact parathyroid hormone (r = 0.72) and NTx (r = 0.84) measured at lactation (P < 0.05).

Conclusions: It appears that adolescent mothers with habitually low calcium intakes recover from lactation-associated bone loss after weaning. The rate of bone accretion, however, may not be sufficient to attain peak bone mass at maturity. Hormones regulating bone turnover during lactation may influence bone recovery in adolescent mothers.
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http://dx.doi.org/10.1093/ajcn/80.5.1322DOI Listing
November 2004

Pregnancy and lactation affect markers of calcium and bone metabolism differently in adolescent and adult women with low calcium intakes.

J Nutr 2002 Aug;132(8):2183-7

Laboratório de Bioquímica Nutricional e de Alimentos, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Brazil.

Physiologic adaptation to the high calcium demand during pregnancy and lactation may be different in adolescents than in adults, particularly at low calcium intake. The aim of this cross-sectional study was to compare biochemical markers of calcium and bone metabolism between adolescent (14-19 y) and adult (21-35 y) women with calcium intake approximately 500 mg/d, in three different physiologic states, i.e., control (nonpregnant, nonlactating; NPNL), pregnant and lactating. Markers of calcium metabolism [serum Ca, P and intact parathyroid hormone (iPTH); urinary Ca and P] and of bone turnover [urinary deoxypyridinoline (D-Pyr) and plasma bone alkaline phosphatase (BAP)] were measured in NPNL (adolescents, n = 12 and adults, n = 25), pregnant (adolescents, n = 30 and adults, n = 36) and lactating (adolescents, n = 19 and adults, n = 26) women. In the NPNL women, iPTH, D-Pyr and BAP were higher (P < 0.001) and urinary Ca was lower (P < 0.001) in adolescents than in adults. Serum iPTH was higher (P < 0.001) and urinary Ca was lower (P < 0.01) in adolescents than in adults also in pregnancy and lactation. Compared with NPNL women, serum Ca decreased (P < 0.001) with pregnancy in adolescents but not in adults. The increase in D-Pyr with pregnancy and lactation was very pronounced in adults ( approximately 130%, P < 0.001) but less in adolescents (<25%, P < 0.01). BAP increased (P < 0.001) with pregnancy and lactation in adults ( approximately 60%) but decreased (P < 0.001) with pregnancy in adolescents ( approximately 13%). Pregnancy and lactation appear to affect bone turnover in adolescent and adult women with low calcium intake differently.
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http://dx.doi.org/10.1093/jn/132.8.2183DOI Listing
August 2002
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