Kenneth J. Ellis

A combination of prebiotic short- and long-chain inulin-type fructans enhances calcium absorption and bone mineralization in young adolescents

BACKGROUND Short-term studies in adolescents have generally shown an enhancement of calcium absorption by inulin-type fructans (prebiotics). Results have been inconsistent; however, and no studies have been conducted to determine whether this effect persists with long-term use. OBJECTIVE The objective was to assess the effects on calcium absorption and bone mineral accretion after 8 wk and 1 y of supplementation with an inulin-type fructan. DESIGN Pubertal adolescents were randomly assigned to receive 8 g/d of a mixed short and long degree of polymerization inulin-type fructan product (fructan group) or maltodextrin placebo (control group). Bone mineral content and bone mineral density were measured before randomization and after 1 y. Calcium absorption was measured with the use of stable isotopes at baseline and 8 wk and 1 y after supplementation. Polymorphisms of the Fok1 vitamin D receptor gene were determined. RESULTS Calcium absorption was significantly greater in the fructan group than in the control group at 8 wk (difference: 8.5 +/- 1.6%; P < 0.001) and at 1 y (difference: 5.9 +/- 2.8%; P = 0.04). An interaction with Fok1 genotype was present such that subjects with an ff genotype had the least initial response to fructan. After 1 y, the fructan group had a greater increment in both whole-body bone mineral content (difference: 35 +/- 16 g; P = 0.03) and whole-body bone mineral density (difference: 0.015 +/- 0.004 g/cm(2); P = 0.01) than did the control group. CONCLUSION Daily consumption of a combination of prebiotic short- and long-chain inulin-type fructans significantly increases calcium absorption and enhances bone mineralization during pubertal growth. Effects of dietary factors on calcium absorption may be modulated by genetic factors, including specific vitamin D receptor gene polymorphisms.

Prevention of Involutional Bone Loss by Exercise

To ascertain whether exercise could prevent involutional bone loss, we studied 18 postmenopausal women, half of whom exercised for 1 h three times a week. Total and regional bone mass were measured before and after 1 year of exercise by the techniques of total-body neutron activation analysis (total body calcium) and photon absorptiometry (bone mineral content) of the distal radius. Total body potassium was measured by whole body counting. Bone mineral content and total body potassium did not change significantly in either group. Total body calcium increased in the exercise group from 781 +/- 95 g of 801 +/- 118 g (SD). In contrast, total body calcium decreased in each subject in the sedentary group. The daily calcium balance derived from the difference in total body calcium measurements was significantly different in the two groups of women (P less than 0.001). These data support the hypothesis that exercise can modify involutional bone loss.

Body Composition during the First 2 Years of Life: An Updated Reference

Normative body composition during the first 2 y of life was derived from a prospective study of 76 children. We present 1) fat free mass (FFM) and its components, and fat mass (FM), 2) incremental growth rates partitioned into chemical components, and 3) age-specific and gender-specific constants for converting chemical and physical components into FFM for children during the first 2 y of life. A multicomponent model based on measurements of total body water (TBW), total body potassium (TBK) and bone mineral content (BMC) was used to estimate FFM and FM at 0.5, 3, 6, 9, 12, 18, and 24 mo of age. TBW was determined by deuterium dilution, TBK by whole body counting, and BMC by dual energy x-ray absorptiometry. FFM was higher in boys than girls between 0.5–18 mo of age (p ≤ 0.05). Percent FM increased on average from 13 to 31% between 0.5 and 3–6 mo, and then gradually declined. Percent FM was significantly higher in girls than in boys at 6 and 9 mo of age (p ≤ 0.02). The components of FFM on a percentage basis changed with age (p = 0.001), but not gender. The protein content of FFM increased gradually with age, while TBW declined (p = 0.001). As a percentage of FFM, osseous mineral increased from 2.0 to 3.4% in boys and from 2.1 to 3.3% in girls between 0.5 and 24 mo (p = 0.001). Density and potassium content of FFM increased gradually with age (p = 0.001). These normative body composition data provide an updated reference upon which to assess normal growth and nutritional status of pediatric populations representative of mixed feeding groups during the first 2 y of life.

Composition of gestational weight gain impacts maternal fat retention and infant birth weight

OBJECTIVE The purpose of this study was to evaluate how changes in gestational weight and body composition affect infant birth weight and maternal fat retention after delivery in underweight, normal-weight and overweight women. STUDY DESIGN We assessed the body composition of 63 women (low body mass index, 17 women; normal body mass index, 34 women; and high body mass index, 12 women) on the basis of measurements of total body nitrogen by prompt-gamma activation analysis, total body potassium by whole body counting, and a multicomponent model based on total body water by deuterium dilution, body volume by densitometry, and bone mineral content by dual energy x-ray absorptiometry (DXA) before pregnancy, at 9, 22, and 36 weeks of gestation, and at 2, 6, and 27 weeks after delivery. Infant weight and length were recorded at birth; infant anthropometry and body composition by DXA were assessed at 2 and 27 weeks of age. RESULTS Gestational weight gain was correlated significantly with gains in total body water, total body potassium, protein, fat-free mass, and fat mass (P=.001-.003). Gains in total body water, total body potassium, protein and fat-free mass did not differ among body mass index groups; however, fat mass gain was higher in the high body mass index group (P=.03). Birth weight was correlated positively with gain in total body water, total body potassium, and fat-free mass (P<.01), but not fat mass. Postpartum weight and fat retention were correlated positively with gestational weight gain (P=.001) and fat mass gain (P=.001) but not with total body water, total body potassium, or fat-free mass gain. CONCLUSION Appropriate, but not excessive, gestational weight gain is needed to optimize infant birth weight and minimize maternal postpartum fat retention.

Vitamin D Receptor Gene Fok1 Polymorphism Predicts Calcium Absorption and Bone Mineral Density in Children

The vitamin D receptor (VDR) gene has been implicated as one of the major genetic components of osteoporosis. We evaluated the relationship between markers of mineral status and restriction fragment length polymorphisms of the VDR gene in 72 healthy children age 7–12 years. Using stable isotope techniques and dual‐energy X‐ray absorptiometry, we measured dietary calcium absorption, bone calcium deposition rates, and total body bone mineral density (BMD). The Fok1 polymorphism at the VDR translation initiation site was significantly associated with BMD (p = 0.02) and calcium absorption (p = 0.04). Children who were FF homozygotes had a mean calcium absorption that was 41.5% greater than those who were ff homozygotes and 17% greater absorption than Ff heterozygotes. BMD was 8.2% greater in the FF genotype than the ff genotype and 4.8% higher than the Ff genotype. These results suggest a substantial relationship between the VDR gene and bone metabolism at one or more levels, including dietary absorption of calcium and BMD in growing children.

Bone mineral changes in young women with hypothalamic amenorrhea treated with oral contraceptives, medroxyprogesterone, or placebo over 12 months

OBJECTIVES The objectives of this study were to assess (1) whether treatment with oral contraceptives, in comparison with medroxyprogesterone and placebo, improved bone mineral in women with hypothalamic amenorrhea and (2) whether treatment with medroxyprogesterone, in comparison with placebo, improved bone mineral in women with hypothalamic oligomenorrhea. STUDY DESIGN The study was a randomized, controlled clinical trial. Twenty-four white women, aged 14 to 28 years, with hypothalamic amenorrhea or oligomenorrhea were prospectively enrolled for a 12-month intervention period. Amenorrheic subjects were randomized to receive oral contraceptives, medroxyprogesterone, or placebo. Oligomenorrheic subjects were randomized to receive medroxyprogesterone or placebo. Bone mineral was measured by dual-energy x-ray absorptiometry at baseline and at 6 and 12 months. RESULTS In amenorrheic subjects spine and total body bone mineral measurements at 12 months were greater in the oral contraceptive group than in the medroxyprogesterone and placebo groups when baseline bone mineral measurements, body weight, and age were controlled for (p < or = 0.05). There were no differences in hip bone mineral calcium and bone mineral density measurements at 12 months among the three groups. In oligomenorrheic subjects there was no detectable improvement in bone mineral associated with medroxyprogesterone use. CONCLUSIONS This study supports the hypothesis that oral contraceptive use in women with hypothalamic amenorrhea will improve lumbar spine and total body bone mineral.

Z Score Prediction Model for Assessment of Bone Mineral Content in Pediatric Diseases

The objective of this study was to develop an anthropometry‐based prediction model for the assessment of bone mineral content (BMC) in children. Dual‐energy X‐ray absorptiometry (DXA) was used to measure whole‐body BMC in a heterogeneous cohort of 982 healthy children, aged 5–18 years, from three ethnic groups (407 European‐ American [EA], 285 black, and 290 Mexican‐American [MA]). The best model was based on log transformations of BMC and height, adjusted for age, gender, and ethnicity. The mean ± SD for the measured/predicted ln ratio was 1.000 ± 0.017 for the calibration population. The model was verified in a second independent group of 588 healthy children (measured/predicted ln ratio = 1.000 ± 0.018). For clinical use, the ratio values were converted to a standardized Z score scale. The whole‐body BMC status of 106 children with various diseases (42 cystic fibrosis [CF], 29 juvenile dermatomyositis [JDM], 15 liver disease [LD], 6 Rett syndrome [RS], and 14 human immunodeficiency virus [HIV]) was evaluated. Thirty‐nine patients had Z scores less than −1.5, which suggest low bone mineral mass. Furthermore, 22 of these patients had severe abnormalities as indicated by Z scores less than −2.5. These preliminary findings indicate that the prediction model should prove useful in determining potential bone mineral deficits in individual pediatric patients.

Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty.

Few studies of the VDR polymorphisms have looked at calcium metabolism or long‐term effects. We measured bone mineralization and calcium metabolic parameters longitudinally in a group of 99 adolescents. We found a significant relationship between calcium absorption and skeletal calcium accretion and the Fok1, but not other VDR or related, genetic polymorphisms. It seems that the Fok1 polymorphism directly affects bone mineralization during pubertal growth through an effect on calcium absorption.

Bone mineral and body composition measurements: cross-calibration of pencil-beam and fan-beam dual-energy X-ray absorptiometers.

Pencil‐beam dual‐energy X‐ray absorptiometers (DXA) are being replaced with instruments that rely solely on fan‐beam technology. However, information has been lacking regarding the translation of bone mineral and body composition data between the two devices. We have compared total body scans using pencil‐beam (Hologic QDR‐2000W) and fan‐beam (Hologic QDR‐4500A) instruments for 33 children (ages 3–18 years) and 14 adults. Bone mineral content (BMC), bone mineral density (BMD), fat, lean, and body fatness (%fat) values were highly correlated (r2 = 0.984–0.998) between the two DXA instruments. The mean differences between the paired measurements were: ΔBMC = 7.5 ± 73.6 g, ΔBMD = 0.0074 ± 0.0252 g/cm2, Δlean = 1.05 ± 1.8 kg, Δfat = −0.77 ± 1.7 kg, and Δ%fat = −0.94% ± 2.5%. The BMC and BMD values were not statistically different, whereas the differences for the body composition values were significant (p < 0.02–0.005). Regression equations are provided for conversion of bone and body composition data between pencil‐beam and fan‐beam values for the whole body. To test the performance of these equations for a second group (23 subjects), predicted values were compared with the measured data obtained using the fan‐beam instrument. The mean differences were −1.0% to 1.4%, except for body fat mass, where the difference was 6.4%. For cross‐sectional studies, the two DXA technologies can be considered equivalent after using the translational equations provided. For longitudinal studies in which small changes in body composition for the individual are to be detected, we recommend that the same DXA instrument be used whenever possible. For example, transition from a pencil‐beam to a fan‐beam instrument could, in extreme cases, result in differences as large as 19% for the estimate of body fat mass.

Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial

BACKGROUND Isoflavones are naturally occurring plant estrogens that are abundant in soy. Although purported to protect against bone loss, the efficacy of soy isoflavone supplementation in the prevention of osteoporosis in postmenopausal women remains controversial. OBJECTIVE Our aim was to test the effect of soy isoflavone supplementation on bone health. DESIGN A multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg of soy hypocotyl aglycone isoflavones plus calcium and vitamin D on bone changes in 403 postmenopausal women. Study subjects were tested annually and changes in whole-body and regional bone mineral density (BMD), bone mineral content (BMC), and T scores were assessed. Changes in serum biochemical markers of bone metabolism were also assessed. RESULTS After study site, soy intake, and pretreatment values were controlled for, subjects receiving a daily supplement with 120 mg soy isoflavones had a statistically significant smaller reduction in whole-body BMD than did the placebo group both at 1 y (P < 0.03) and at 2 y (P < 0.05) of treatment. Smaller decreases in whole-body BMD T score were observed among this group of women at 1 y (P < 0.03) but not at 2 y of treatment. When compared with the placebo, soy isoflavone supplementation had no effect on changes in regional BMD, BMC, T scores, or biochemical markers of bone metabolism. CONCLUSION Daily supplementation with 120 mg soy hypocotyl isoflavones reduces whole-body bone loss but does not slow bone loss at common fracture sites in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.