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Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia.

ABSTRACT: BACKGROUND: This study investigates pharmacogenetic risk factors for bone mineral (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic leukemia DESIGN AND METHODS: We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2/GATA), collagen type I alpha 1 (SpI), estrogen receptor 1 (ESR1: PvuII/XbaI), glucocorticoid receptor (BclI)) on body composition, BM(A)D and fracture risk during dexamethasone-based pediatric acute lymphoblastic leukemia treatment. Body composition and BMD were measured repeatedly during and after treatment using dual energy X-ray absorptiometry. RESULTS: Non-carriers of VDR 5'-end (Cdx-2/GATA) haplotype 3 revealed a significant larger fat gain than carriers (Delta%fat: non-carriers: +1.76SDS, carriers: +0.77SDS, P<0.001). At diagnosis and during therapy, lumbar spine BMD was significantly higher in non-carriers of VDR 5'-end (Cdx-2/GATA) haplotype 3 than in carriers. The other SNPs did not influence BMD or fracture risk during/after treatment. The year after treatment completion, lean body mass increased in non-carriers of ESR1 (PvuII/XbaI) haplotype 3 and decreased in carriers (Delta lean body mass: non-carriers:+0.28SDS, carriers: -0.55SDS, P<0.01). CONCLUSIONS: Only VDR 5'-end (Cdx-2/GATA) haplotype 3 was identified as protective factor against excessive fat gain and as a risk factor for lower lumbar spine BMD during treatment. Carrying ESR1 (PvuII/XbaI) haplotype 3 negatively influenced recovery of lean body mass after pediatric acute lymphoblastic leukemia treatment.

SUBMITTER: te Winkel ML

PROVIDER: S-EPMC2864381 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia.

te Winkel Mariël L ML van Beek Robert D RD de Muinck Keizer-Schrama Sabine M P F SM Uitterlinden André G AG Hop Wim C J WC Pieters Rob R van den Heuvel-Eibrink Marry M MM

Haematologica 20091216 5

<h4>Background</h4>This study investigates pharmacogenetic risk factors for bone mineral (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic leukemia<h4>Design and methods</h4>We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2/GATA), collagen type I alpha 1 (SpI), estrogen receptor 1 (ESR1: PvuII/XbaI), glucocorticoid receptor (BclI)) on body composition, BM(A)D and fracture risk during dexamethasone-based pediatric acu ...[more]

PMID: 20015871

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Project description:BackgroundThe impact of the type and the severity of disability on whole-body and regional body composition (BC), and bone mineral density (BMD) must be considered for dietary advice in athletes with a physical impairment (PI). This study aimed to investigate the impact of the type and the severity of disability on BC, the pattern of distribution of fat mass at the regional level, and BMD in athletes with a PI.MethodsForty-two male athletes with spinal cord injury (SCI, n = 24; age = 40.04 ± 9.95 years, Body Mass Index [BMI] = 23.07 ± 4.01 kg/m2) or unilateral lower limb amputation (AMP, n = 18; age = 34.39 ± 9.19 years, BMI = 22.81 ± 2.63 kg/m2) underwent a Dual-Energy X-Ray Absorptiometry scan. Each athlete with a PI was matched by age with an able-bodied athlete (AB, n = 42; age = 37.81 ± 10.31 years, BMI = 23.94 ± 1.8 kg/m2).ResultsOne-Way Analysis of Variance showed significant differences between the SCI, AMP and AB groups for percentage fat mass (%FM) (P < 0.001, eta squared = 0.440). Post-hoc analysis with Bonferroni's correction showed that athletes with SCI had significantly higher %FM vs. the AMP and AB groups (25.45 ± 5.99%, 21.45 ± 4.21% and 16.69 ± 2.56%, respectively; P = 0.008 vs. AMP and P < 0.001 vs. AB). The %FM was also significantly higher in the AMP vs. the AB group (P < 0.001). Whole-body BMD was negatively affected in SCI athletes, with about half of them showing osteopenia or osteoporosis. In fact, the mean BMD and T-score values in the SCI group (1.07 ± 0.09 g/cm2 and -1.25 ± 0.85, respectively) were significantly lower in comparison with the AB group (P = 0.001 for both) as well as the AMP group (P = 0.008 for both). The type of disability affected BC and BMD in the trunk, android, gynoid and leg regions in SCI athletes and the impaired leg only in AMP athletes.ConclusionsIn conclusion, the type of disability and, partly, the severity of PI impact on BC and BMD in athletes with a PI. Nutritionists, sports medicine doctors, clinicians, coaches and physical conditioners should consider athletes with SCI or AMP separately. Athletes with a PI would benefit from specific nutrition and training programs taking into account the type of their disability.

Project description:BackgroundLow bone mineral density (BMD) and subsequent skeletal fragility have emerged as a long-term complication of phenylketonuria (PKU).ObjectiveTo determine if there are differences in BMD and body composition between male and female participants with PKU.MethodsFrom our randomized, crossover trial [1] of participants with early-treated PKU who consumed a low-phenylalanine (Phe) diet combined with amino acid medical foods (AA-MF) or glycomacropeptide medical foods (GMP-MF), a subset of 15 participants (6 males, 9 females, aged 15-50 y, 8 classical and 7 variant PKU) completed one dual energy X-ray absorptiometry (DXA) scan and 3-day food records after each dietary treatment. Participants reported lifelong compliance with AA-MF. In a crossover design, 8 participants (4 males, 4 females, aged 16-35 y) provided a 24-h urine collection after consuming AA-MF or GMP-MF for 1-3 weeks each.ResultsMale participants had significantly lower mean total body BMD Z-scores (means ± SE, males = - 0.9 ± 0.4; females, 0.2 ± 0.3; p = 0.01) and tended to have lower mean L1-4 spine and total femur BMD Z-scores compared to female participants. Only 50% percent of male participants had total body BMD Z-scores above - 1.0 compared to 100% of females (p = 0.06). Total femur Z-scores were negatively correlated with intake of AA-MF (r = - 0.58; p = 0.048). Males tended to consume more grams of protein equivalents per day from AA-MF (means ± SE, males: 67 ± 6 g, females: 52 ± 4 g; p = 0.057). Males and females demonstrated similar urinary excretion of renal net acid, magnesium and sulfate; males showed a trend for higher urinary calcium excretion compared to females (means ± SE, males: 339 ± 75 mg/d, females: 228 ± 69 mg/d; p = 0.13). Females had a greater percentage of total fat mass compared to males (means ± SE, males: 24.5 ± 4.8%, females: 36.5 ± 2.5%; p = 0.047). Mean appendicular lean mass index was similar between males and females. Male participants had low-normal lean mass based on the appendicular lean mass index.ConclusionsMales with PKU have lower BMD compared with females with PKU that may be related to higher intake of AA-MF and greater calcium excretion. The trial was registered at www.clinicaltrials.gov as NCT01428258.

Project description:BackgroundThe aim of the study were to analyze the lumbar volumetric bone mineral density (BMD), fat distribution and changes of skeletal muscle with quantitative computed tomography (QCT) in postmenopausal women with type 2 diabetes mellitus (T2DM), and to evaluate the relationship between body composition and BMD.MethodsOne hundred seventy-seven postmenopausal women with T2DM and 136 postmenopausal women without diabetes were included in the study and were divided into two groups according to age, 50-65 years age group and over 65 years of age group. The lumbar BMD (L1-L3), visceral fat mass (VFM), visceral fat area (VFA), subcutaneous fat mass (SFM), subcutaneous fat area (SFA), psoas major mass (PMM) and psoas major area (PMA) of each group were compared. Univariable and multivariable linear regression analysis were used to analyze the contribution of each variable to BMD in postmenopausal women with T2DM.ResultsIn women aged 50-65, the patients in the T2DM group had higher body mass index (BMI), VFM, VFA, and SFM (p < 0.05), compared with non-T2DM group. Over 65 years old, the BMI, BMD, VFM, VFA, and SFM was found to be much higher in participants with T2DM than in non-T2DM group (p < 0.05). Compared with women aged in 50-65 years old, those over 65 years old had higher VFA and VFM and lower BMD (p < 0.05), whether in the T2DM group or the non-T2DM group. Age, VFA and VFM were negatively correlated with BMD (r = -0.590, p ≤ 0.001; r = -0.179, p = 0.017; r = -0.155, p = 0.040, respectively). After adjusting for age, VFM and VFA were no longer correlated with BMD. No correlations between fat distribution or psoas major muscle and BMD in postmenopausal women with T2DM were observed.ConclusionsT2DM can affect abdominal fat deposition in postmenopausal women. Postmenopausal elderly women with diabetes have higher BMD than normal elderly women. There was no correlation between fat distribution or psoas major and BMD in postmenopausal women with diabetes mellitus.

Project description:Objective: The objective of this study was to evaluate whether evolution of bone mineral density (BMD) is associated with the thyroid hormone profile in a cohort of euthyroid women with no other known diseases within 1 year. Methods: This was a prospective cohort study conducted at the University of Campinas, Brazil. We used a database with 52 women aged 20-39 who were followed for 1 year in a family planning outpatient clinic. The inclusion criteria were body mass index (BMI) <30 kg/m2, no known diseases/medication use, fasting glucose <100 mg/dl, and 2 h glucose after a 75 g oral glucose load <140 mg/dl. The women were divided into groups of normal weight (n = 30) and overweight (n = 22). The main outcomes were BMD measured by dual-energy x-ray absorptiometry (DXA) and thyroid hormone profile (thyrotropin TSH, free triiodothyronine FT3, free thyroxine FT4, and T3/T4 ratio); other variables were body composition (DXA), calcium metabolism markers, and life habits. We used a repeated measures analysis of variance (ANOVA) and multiple regression analyses to evaluate associations. Results: At the baseline data collection, overweight women showed a higher T3/T4 ratio, leptin, calcium, BMD in the lumbar spine and total femur, total mass, mass, and percentage of fat mass than normal weight women. At 12 months, both groups had increased FT4, calcium, ALP, femoral neck BMD, and total mass by time effect. The normal weight group presented a decrease of vitamin D when compared to the baseline. Increased BMD of the femoral neck was associated with moderate coffee intake, and as such, there were no associations found between this increase and the thyroid hormone profile. Leptin and ALP were associated with total mass variation, while leptin and PTH were associated with fat mass variation. The normal BMI was inversely associated with the variation of total mass, mass, and percentage of fat mass, and engaging in regular physical activity was inversely associated with fat mass variation. Conclusions: In this sample of euthyroid healthy women who were both normal weight and overweight, the thyroid hormone profile was not associated with variations in bone mineral density and body composition after a 1 year follow-up.

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Dataset Information

Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia.

Publications

Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia.

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