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1.
Osteoporos Int ; 28(4): 1215-1223, 2017 04.
Article in English | MEDLINE | ID: mdl-27928628

ABSTRACT

The rare, long-lived radiotracer, 41Ca, measured by accelerator mass spectrometry in the urine or serum following incorporation into the bone provides an ultra-sensitive tool to assess changes in bone calcium balance in response to an intervention. Changes in bone balance can be followed for years with one small dose that is both radiologically and biologically non-invasive. Sequential interventions can be compared, with greater precision than they can with biochemical markers of bone turnover and with greater power than with bone densitometry. This method is especially useful to screen interventions over a period of weeks. The development and validation of this tool and its applications are reviewed. Mini abstract: Use of 41Ca measured in the urine or blood by accelerator mass spectrometry to assess bone balance provides a tool to compare the relative efficacy of multiple interventions. This perspective provides insights in the use of this novel method and comparisons with more traditional methods for evaluating the efficacy of interventions.


Subject(s)
Bone Remodeling/physiology , Bone and Bones/metabolism , Calcium Radioisotopes , Animals , Calcium/metabolism , Calcium Radioisotopes/administration & dosage , Calcium Radioisotopes/urine , Humans , Models, Animal
2.
J Clin Endocrinol Metab ; 99(9): 3240-6, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24926952

ABSTRACT

CONTEXT: Although animal studies suggest that adenovirus 36 (Ad36) infection is linked to obesity and systemic inflammation, human data are scant and equivocal. OBJECTIVE: Associations of Ad36 infection with total body adiposity and inflammatory-related markers were determined in 291 children aged 9-13 years (50% female, 49% black). DESIGN: Fasting blood samples were measured for presence of Ad36-specific antibodies and TNF-α, IL-6, vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). Fat mass and fat-free soft tissue mass were measured by dual-energy X-ray absorptiometry. RESULTS: The overall prevalence of Ad36 seropositivity [Ad36(+)] was 42%. There was a higher percentage of Ad36(+) children in the highest tertiles of TNF-α and IL-6 compared with their respective middle and lowest tertiles (both P < .03). There was also a trend toward a higher prevalence of Ad36(+) children in the highest tertile of VEGF compared with tertiles 1 and 2 (P = .05). Multinomial logistic regression, adjusting for age, race, sex, and fat-free soft tissue mass, revealed that compared with children with the lowest TNF-α, IL-6, and VEGF levels (tertile 1), the adjusted odds ratios for Ad36(+) were 2.2 [95% confidence interval (CI) 1.2-4.0], 2.4 (95% CI 1.4-4.0), and 1.8 (95% CI 1.0-3.3), respectively, for those in the highest TNF-α, IL-6, and VEGF levels (tertile 3). No association was observed between Ad36(+) and greater levels of fat mass or MCP-1 (all P > .05). CONCLUSIONS: In children, our data suggest that Ad36(+) may be associated with biomarkers implicated in inflammation but not with greater levels of fat mass.


Subject(s)
Adenoviridae/immunology , Adenovirus Infections, Human/epidemiology , Adenovirus Infections, Human/immunology , Adiposity/immunology , Inflammation/epidemiology , Inflammation/immunology , Adolescent , Antibodies, Viral/blood , Biomarkers/blood , Chemokine CCL2/blood , Child , Female , Humans , Interleukin-6/blood , Male , Odds Ratio , Prevalence , Seroepidemiologic Studies , Tumor Necrosis Factor-alpha/blood , Vascular Endothelial Growth Factor A/blood
3.
Osteoporos Int ; 25(10): 2471-5, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24969137

ABSTRACT

SUMMARY: Urinary excretion of calcium tracers in labeled individuals decreases in response to antiresorptive therapy, providing a tool to rapidly screen potential therapies. Using teriparatide, we demonstrate in this study that anabolic therapy also decreases tracer excretion, confirming that this method can also be used to screen potential anabolic therapies. INTRODUCTION: Changes in urinary excretion of calcium tracers from a labeled skeleton may be a rapid and sensitive method to screen potential therapies for osteoporosis. This method has been used to screen antiresorptive therapies, but the effect of anabolic therapies on tracer excretion is unknown. METHODS: Eight-month-old female Sprague Dawley rats (n = 11) were given 50 µCi (45)Ca iv. After a 1-month equilibration period, baseline urinary (45)Ca excretion and total bone mineral content (BMC) were measured. Rats were then treated with 30 µg/kg teriparatide sc per day, a bone anabolic agent, for 80 days. Urine was collected throughout the study and analyzed for (45)Ca and total Ca, and BMC was measured at the beginning and end of the study. RESULTS: Teriparatide decreased urinary (45)Ca excretion by 52.1 % and increased BMC by 21.7 %. The change in bone calcium retention as determined by the ratio of (45)Ca to total Ca excretion in urine from day 6 through 15 of teriparatide treatment was significantly correlated (p = 0.036) with the change in BMC after 80 days of teriparatide treatment. CONCLUSION: Urinary excretion of calcium tracers from labeled bone is an effective method to rapidly screen potential anabolic therapies for osteoporosis.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Calcium Radioisotopes , Drug Evaluation, Preclinical/methods , Osteoporosis/drug therapy , Teriparatide/therapeutic use , Animals , Bone Density/drug effects , Bone Density Conservation Agents/pharmacology , Bone and Bones/metabolism , Calcium Radioisotopes/urine , Female , Osteoporosis/physiopathology , Radiopharmaceuticals/urine , Rats, Sprague-Dawley , Teriparatide/pharmacology
4.
Osteoporos Int ; 25(7): 1905-15, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24740476

ABSTRACT

UNLABELLED: The interaction of habitual Ca and vitamin D intake from preovariectomy to 4 months postovariectomy on bone and Ca metabolism was assessed. Higher Ca intake suppressed net bone turnover, and both nutrients independently benefitted trabecular structure. Habitual intake of adequate Ca and ~50 nmol/L vitamin D status is most beneficial. INTRODUCTION: Dietary strategies to benefit bone are typically tested prior to or after menopause but not through menopause transition. We investigated the interaction of Ca and vitamin D status on Ca absorption, bone remodeling, Ca kinetics, and bone strength as rats transitioned through estrogen deficiency. METHODS: Sprague Dawley rats were randomized at 8 weeks to 0.2 or 1.0 % Ca and 50, 100, or 1,000 IU (1.25, 2.5, or 25 µg) vitamin D/kg diet (2 × 3 factorial design) and ovariectomized at 12 weeks. Urinary (45)Ca excretion from deep-labeled bone was used to assess net bone turnover weekly. Ca kinetics was performed between 25 and 28 weeks. Rats were killed at 29 weeks. Femoral and tibiae structure (by µCT), dynamic histomorphometry, and bone Ca content were assessed. RESULTS: Mean 25(OH)D for rats on the 50, 100, 1,000 IU vitamin D/kg diet were 32, 54, and 175 nmol/L, respectively. Higher Ca intake ameliorated net bone turnover, reduced fractional Ca absorption and bone resorption, and increased net Ca absorption. Tibial and femoral trabecular structures were enhanced independently by higher Ca and vitamin D intake. Tibial bone width and fracture resistance were enhanced by higher vitamin D intake. Dynamic histomorphometry in the tibia was not affected by either nutrient. A Ca × vitamin D interaction existed in femur length, tibial Ca content, and mass of the soft tissue/extracellular fluid compartment. CONCLUSIONS: Adequate Ca intake and serum 25(OH)D level of 50 nmol/L provided the most benefit for bone health, mostly through independent effects of Ca and vitamin D.


Subject(s)
Bone Remodeling/physiology , Calcium, Dietary/administration & dosage , Menopause/physiology , Vitamin D/administration & dosage , Animals , Biomechanical Phenomena , Bone Density/drug effects , Bone Density/physiology , Bone Remodeling/drug effects , Bone Resorption/physiopathology , Bone Resorption/prevention & control , Calcium Radioisotopes , Calcium, Dietary/pharmacokinetics , Calcium, Dietary/pharmacology , Feces/chemistry , Female , Intestinal Absorption/physiology , Menopause/metabolism , Ovariectomy , Rats, Sprague-Dawley , Tibia/physiology , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D/pharmacology
5.
J Clin Endocrinol Metab ; 98(12): 4816-25, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24092833

ABSTRACT

CONTEXT: Changes in serum vitamin D metabolites and calcium absorption with varying doses of oral vitamin D3 in healthy children are unknown. OBJECTIVE: Our objective was to examine the dose-response effects of supplemental vitamin D3 on serum vitamin D metabolites and calcium absorption in children living at two U.S. latitudes. DESIGN: Black and white children (n = 323) participated in a multisite (U.S. latitudes 34° N and 40° N), triple-masked trial. Children were randomized to receive oral vitamin D3 (0, 400, 1000, 2000, and 4000 IU/d) and were sampled over 12 weeks in winter. Serum 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured using RIA and intact PTH (iPTH) by immunoradiometric assay. Fractional calcium absorption was determined from an oral stable isotope 44Ca (5 mg) in a 150-mg calcium meal. Nonlinear and linear regression models were fit for vitamin D metabolites, iPTH, and calcium absorption. RESULTS: The mean baseline 25(OH)D value for the entire sample was 70.0 nmol/L. Increases in 25(OH)D depended on dose with 12-week changes ranging from -10 nmol/L for placebo to 76 nmol/L for 4000 IU. Larger 25(OH)D gains were observed for whites vs blacks at the highest dose (P < .01). Gains for 1,25(OH)2D were not significant (P = .07), and decreases in iPTH were not dose-dependent. There was no dose effect of vitamin D on fractional calcium absorption when adjusted for pill compliance, race, sex, or baseline 25(OH)D. CONCLUSION: Large increases in serum 25(OH)D with vitamin D3 supplementation did not increase calcium absorption in healthy children living at 2 different latitudes. Supplementation with 400 IU/d was sufficient to maintain wintertime 25(OH)D concentrations in healthy black, but not white, children.


Subject(s)
Calcium, Dietary/metabolism , Child Development , Cholecalciferol/administration & dosage , Dietary Supplements , Intestinal Absorption , Models, Biological , Vitamin D Deficiency/prevention & control , Adolescent , Black or African American , Calcifediol/blood , Calcifediol/metabolism , Calcitriol/blood , Calcitriol/metabolism , Child , Cholecalciferol/adverse effects , Cholecalciferol/metabolism , Cholecalciferol/therapeutic use , Dietary Supplements/adverse effects , Double-Blind Method , Female , Georgia , Humans , Indiana , Intestinal Absorption/ethnology , Male , Parathyroid Hormone/blood , Parathyroid Hormone/metabolism , Seasons , Sunlight , Vitamin D Deficiency/blood , Vitamin D Deficiency/ethnology , Vitamin D Deficiency/metabolism , White People
6.
Bone ; 51(5): 888-95, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22944607

ABSTRACT

UNLABELLED: Variation in structural geometry is present in adulthood, but when this variation arises and what influences this variation prior to adulthood remains poorly understood. Ethnicity is commonly the focus of research of skeletal integrity and appears to explain some of the variation in quantification of bone tissue. However, why ethnicity explains variation in skeletal integrity is unclear. METHODS: Here we examine predictors of bone cross sectional area (CSA) and section modulus (Z), measured using dual-energy X-ray absorptiometry (DXA) and the Advanced Hip Analysis (AHA) program at the narrow neck of the femur in adolescent (9-14 years) girls (n=479) living in the United States who were classified as Asian, Hispanic, or white if the subject was 75% of a given group based on parental reported ethnicity. Protocols for measuring height and weight follow standardized procedures. Total body lean mass (LM) and total body fat mass (FM) were quantified in kilograms using DXA. Total dietary and total dairy calcium intakes from the previous month were estimated by the use of an electronic semi-quantitative food frequency questionnaire (eFFQ). Physical activity was estimated for the previous year by a validated self-administered modifiable activity questionnaire for adolescents with energy expenditure calculated from the metabolic equivalent (MET) values from the Compendium of Physical Activities. Multiple regression models were developed to predict CSA and Z. RESULTS: Age, time from menarche, total body lean mass (LM), total body fat mass (FM), height, total calcium, and total dairy calcium all shared a significant (p<0.05), positive relationship with CSA. Age, time from menarche, LM, FM, and height shared significant (p<0.05), positive relationships with Z. For both CSA and Z, LM was the most important covariate. Physical activity was not a significant predictor of geometry at the femoral neck (p≥0.339), even after removing LM as a covariate. After adjusting for covariates, ethnicity was not a significant predictor in regression models for CSA and Z. CONCLUSION: Variability in bone geometry at the narrow neck of the femur is best explained by body size and pubertal maturation. After controlling for these covariates there were no differences in bone geometry between ethnic groups.


Subject(s)
Body Size/physiology , Puberty/physiology , Adolescent , Asian People , Body Size/ethnology , Child , Female , Femur , Humans , Puberty/ethnology , United States , White People
7.
Osteoporos Int ; 22(6): 1829-34, 2011 Jun.
Article in English | MEDLINE | ID: mdl-20936404

ABSTRACT

UNLABELLED: We extended a simple oral method for estimating fractional calcium absorption determined by double isotopic methods using radioactive or stable isotope across wide age of adult women. Fractional calcium absorption can be estimated by using either a radioactive or stable oral isotope across the entire age spectrum of adult women. INTRODUCTION: A method for estimating fractional calcium absorption using a single serum collection following a single oral radioactive isotopic tracer has been validated against a classical double isotopic tracer ratio method in adults. Our goal was to extend this simplified method to include use of stable isotopes and a broad age range. METHODS: We used our database of 56 observations from 26 white adult women aged 19-67 years receiving either radioactive or stable isotopes. Reference values for fractional calcium absorption were determined from 24-h double isotopic ratios in serum and urine and from full kinetic modeling. RESULTS: Equations for estimating fractional calcium absorption were developed from isotopic enrichment in serum and urine from an oral tracer and measures of body size using the multiple linear regression analysis. Equations using a 4- to 6-h sample following an oral dose of either a stable or radioactive isotope corrected for body size were highly correlated with the reference values for fractional calcium absorption across different aged populations (r > 0.8, p < 0.001). CONCLUSION: Fractional calcium absorption can be estimated by a single oral tracer method using either radioactive or stable calcium isotopes across the entire age spectrum in healthy white adult women.


Subject(s)
Calcium/pharmacokinetics , Intestinal Absorption/physiology , Administration, Oral , Adult , Aged , Body Size , Calcium/blood , Calcium/urine , Calcium Isotopes , Calcium Radioisotopes , Female , Humans , Middle Aged , Radioisotope Dilution Technique , Reference Values , Reproducibility of Results , Young Adult
8.
Osteoporos Int ; 22(1): 159-66, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20358361

ABSTRACT

UNLABELLED: We validated a single oral isotope method for estimating fractional calcium absorption determined by double isotope methods in adolescents. Developed equations with an oral isotope including a single blood draw or spot urine collection can be used to evaluate fractional calcium absorption in adolescents which allows flexibility in developing protocols. INTRODUCTION: This study was designed to develop and validate a simpler, less expensive single oral isotope method for determining fractional calcium (Ca) absorption in adolescents. METHODS: We used our database of 31 observations from ten white and 12 black adolescent girls aged 10-15 years who participated in metabolic and kinetic studies. Tracer data following oral ((44)Ca) and intravenous (IV, (42)Ca) administration of calcium stable isotopes and samples in serum and urine from various time points up to 4 days were used to develop methods using multiple regression analysis based on a single measurement of enriched stable isotope/tracee defined as tracer/tracee (TT) in serum (TT(serum)) or urine (TT(urine)). Reference values for fractional calcium absorption were from oral/IV stable isotope ratios in 24-h serum or urine and full kinetic modeling. RESULTS: The strongest equation using a single blood sample had R (2) = 0.94 (p < 0.001): fractional Ca absorption = 1.3340(4-h TT(serum))(0.7872) BSA(1.7132)e ((-0.01652 PMA)), where BSA is body surface area and PMA is post-menarcheal age. The strongest equation using a single urine sample had R (2) = 0.95 (p < 0.001): fractional Ca absorption = 2.3088 (5-12 h TT(urine))(0.8208) BSA(1.5260)e ((-0.01850 PMA)). Equations were also developed with Tanner score. An external data set of Asian adolescent boys and girls was used to validate the equations. CONCLUSION: Equations using an oral isotope and a single blood draw or urine collection for determining fractional calcium absorption were successfully validated in healthy, non-obese white and black adolescent girls aged 10-15 years. The equations well-predicted fractional calcium absorption in Asian adolescent boys and girls.


Subject(s)
Calcium Isotopes , Intestinal Absorption/physiology , Administration, Oral , Adolescent , Calcium Isotopes/administration & dosage , Child , Female , Humans , Injections, Intravenous , Models, Biological , Radioisotope Dilution Technique , Reference Values
9.
Osteoporos Int ; 22(1): 153-7, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20480145

ABSTRACT

UNLABELLED: Urinary excretion of tritiated tetracycline ((3)H-TC) and (41)Ca tracers was validated as reflecting skeletal disappearance of these bone-seeking tracers as a direct measure of bone turnover following ovariectomy in rats. INTRODUCTION: Tritiated tetracycline ((3)H-TC) and Ca tracers have been used to measure bone resorption in animal models, but urinary excretion of these labels has not been directly compared to skeletal turnover. We aimed to evaluate the use of bone-seeking labels by comparing label release into urine with label in the skeleton when bone turnover was perturbed following ovariectomy. METHODS: Sixty-four 6-month-old ovariectomized (OVX) rats were randomized to one of eight groups in a 2 × 4 design that differed in time of (3)H-TC and (41)Ca administration following ovariectomy (1 month, when bone turnover would be accelerated following estrogen depletion or 3 months when bone loss due to OVX had slowed down) and time of euthanasia (1 week, 1 month, 3 months, and 6 months post-dose). Twenty-four-hour urine pools over two to four consecutive days and total skeleton were collected and recovered for the assessment of (3)H-TC and (41)Ca. RESULTS: Urinary (3)H-TC levels reflected skeletal (3)H-TC levels (r = 0.93; p < 0.0001) over a wide range of bone turnover rates in response to an intervention. Urinary (41)Ca and (3)H-TC excretion were highly correlated (r = 0.95, p < 0.0001). CONCLUSION: This study confirms that bone-seeking label excretion into the urine directly measures bone turnover.


Subject(s)
Biomarkers/urine , Bone Resorption/diagnosis , Animals , Bone Remodeling/physiology , Bone Resorption/etiology , Calcium Radioisotopes/pharmacokinetics , Disease Models, Animal , Female , Femur/metabolism , Lumbar Vertebrae/metabolism , Ovariectomy , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Tetracycline/pharmacokinetics , Tibia/metabolism , Tritium/pharmacokinetics
10.
J Clin Endocrinol Metab ; 94(10): 3798-805, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19584189

ABSTRACT

INTRODUCTION: Reduction of ovarian estrogen secretion at menopause increases net bone resorption and leads to bone loss. Isoflavones have been reported to protect bone from estrogen deficiency, but their modest effects on bone resorption have been difficult to measure with traditional analytical methods. METHODS: In this randomized-order, crossover, blinded trial in 11 healthy postmenopausal women, we compared four commercial sources of isoflavones from soy cotyledon, soy germ, kudzu, and red clover and a positive control of oral 1 mg estradiol combined with 2.5 mg medroxyprogesterone or 5 mg/d oral risedronate (Actonel) for their antiresorptive effects on bone using novel (41)Ca methodology. RESULTS: Risedronate and estrogen plus progesterone decreased net bone resorption measured by urinary (41)Ca by 22 and 24%, respectively (P < 0.0001). Despite serum isoflavone profiles indicating bioavailability of the phytoestrogens, only soy isoflavones from the cotyledon and germ significantly decreased net bone resorption by 9% (P = 0.0002) and 5% (P = 0.03), respectively. Calcium absorption and biochemical markers of bone turnover were not influenced by interventions. CONCLUSIONS: Dietary supplements containing genistein-like isoflavones demonstrated a significant but modest ability to suppress net bone resorption in postmenopausal women at the doses supplied in this study over a 50-d intervention period.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Resorption/prevention & control , Calcium Radioisotopes/metabolism , Dietary Supplements , Estradiol/therapeutic use , Etidronic Acid/analogs & derivatives , Isoflavones/therapeutic use , Medroxyprogesterone/therapeutic use , Osteoporosis, Postmenopausal/prevention & control , Phytoestrogens/therapeutic use , Aged , Analysis of Variance , Bone Density Conservation Agents/pharmacology , Calcium/metabolism , Cotyledon , Cross-Over Studies , Estradiol/pharmacology , Etidronic Acid/pharmacology , Etidronic Acid/therapeutic use , Female , Genistein/pharmacology , Genistein/therapeutic use , Humans , Isoflavones/blood , Isoflavones/pharmacology , Linear Models , Medroxyprogesterone/pharmacology , Middle Aged , Phytoestrogens/pharmacology , Plant Preparations/pharmacology , Plant Preparations/therapeutic use , Pueraria , Risedronic Acid , Single-Blind Method , Glycine max , Treatment Outcome , Trifolium
11.
Calcif Tissue Int ; 81(5): 352-63, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17989943

ABSTRACT

Differences in bone among racial/ethnic groups may be explained by differences in body size and shape. Previous studies have not completely explained differences among white, Asian, and Hispanic groups during growth. To determine racial/ethnic differences and predictors of bone mass in early pubertal girls, we measured bone mineral content (BMC) in white, Hispanic, and Asian sixth-grade girls across six states in the United States. We developed models for predicting BMC for the total-body, distal radius, total-hip, and lumbar spine for 748 subjects. For each of the bone sites, the corresponding area from dual-energy X-ray absorptiometry (DXA) was a strong predictor of BMC, with correlations ranging 0.78-0.98, confirming that larger subjects have more BMC. Anthropometric measures of bone area were nearly as effective as bone area from DXA at predicting BMC. For total-body, distal radius, lumbar spine, and total-hip BMC, racial/ethnic differences were explained by differences in bone area, sexual maturity, physical activity, and dairy calcium intake. Bone size explained most of the racial/ethnic differences in BMC, although behavioral indicators were also significant predictors of BMC.


Subject(s)
Aging/physiology , Bone Density/physiology , Bone Development/physiology , Puberty/physiology , Racial Groups , Absorptiometry, Photon , Anthropometry , Asian People , Body Height/physiology , Calcium, Dietary/metabolism , Child , Cross-Sectional Studies , Female , Growth and Development/physiology , Hispanic or Latino , Humans , Motor Activity/physiology , Predictive Value of Tests , Skeleton , White People
12.
J Clin Endocrinol Metab ; 92(2): 577-82, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17148567

ABSTRACT

INTRODUCTION: The purpose of this 3-way crossover study was to identify the effective dose of soy protein isolate enriched with isoflavones for suppressing bone resorption in postmenopausal women using a novel, rapid assessment of antibone resorbing treatments. METHODS: Thirteen postmenopausal women (>or=6 yr since menopause) were predosed with 41Ca iv. After a 200-d baseline period, subjects were given 43 g soy protein/d that contained 0, 97.5, or 135.5 mg total isoflavones in randomized order. The soy protein isolate powder was incorporated into baked products and beverages. Each 50-d intervention phase was preceded by a 50-d pretreatment phase for comparison. Serum isoflavone levels and biochemical markers were measured at the end of each phase. Twenty-four-hour urine samples were collected approximately every 10 d during each phase for 41Ca/Ca analysis by accelerator mass spectrometry. RESULTS: Serum isoflavone levels reflected the amount of isoflavones consumed in a dose-dependent manner. None of the isoflavone levels had a significant effect on biochemical markers of bone turnover, urinary cross-linked N teleopeptides of type I collagen and serum osteocalcin, or bone turnover as assessed by urinary 41Ca/Ca ratios. CONCLUSIONS: Soy protein with isoflavone doses of up to 135.5 mg/d did not suppress bone resorption in postmenopausal women. This is the first efficacy trial using the novel technique of urinary 41Ca excretion from prelabeled bone.


Subject(s)
Bone Resorption/drug therapy , Bone Resorption/metabolism , Bone and Bones/metabolism , Isoflavones/administration & dosage , Phytotherapy , Soybean Proteins/administration & dosage , Adult , Calcium/urine , Calcium Radioisotopes/urine , Collagen Type I/urine , Cross-Over Studies , Double-Blind Method , Female , Humans , Middle Aged , Osteocalcin/urine , Peptides/urine , Postmenopause
13.
Int J Obes (Lond) ; 30(1): 94-9, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16158089

ABSTRACT

OBJECTIVE: To investigate the relationship of parathyroid hormone (PTH) with dietary calcium and changes in body composition. DESIGN: Cross-sectional and 1-year longitudinal trial. SUBJECTS: Normal-weight young women (age: 18-31), 155 subjects analyzed at baseline, and data for 41 subjects analyzed prospectively between baseline and 12 months. MEASUREMENTS: Levels of fasting serum calcium and PTH, intakes of calcium (3-day diet records), and total body weight and body composition (dual energy X-ray absorptiometry). RESULTS: Baseline dietary calcium, regardless of whether unadjusted or adjusted for energy intake, did not predict baseline levels of fasting serum PTH. Change in dietary calcium also did not predict change in serum PTH. However, log PTH was significantly correlated with body fat mass (R = 0.27), but not lean mass at baseline (n = 155), independent of serum calcium (corrected R = 0.25). Further, 12-month changes (n = 41) in log PTH positively predicted the 12-month change in body weight (R = 0.32) and body fat (R = 0.32), but not lean mass even when controlled for age or change in serum calcium. CONCLUSION: Fasting serum PTH was associated with increased fat mass, in both cross-sectional and prospective analysis. Thus, serum PTH may play a role in the regulation of body fat mass in young women.


Subject(s)
Adiposity/physiology , Parathyroid Hormone/blood , Absorptiometry, Photon/methods , Adolescent , Adult , Body Composition , Body Weight/physiology , Calcium/blood , Calcium, Dietary/administration & dosage , Cross-Sectional Studies , Female , Humans , Prospective Studies
14.
J Food Prot ; 68(12): 2679-85, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16355842

ABSTRACT

Toxicity equivalents is a measure of "dioxin-like" toxicity contributed by polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (dioxins), and polychlorinated dibenzofurans (furans). Calculation of toxicity equivalents require the use of analytical procedures that are expensive and slow, making them impractical for routine analysis. U.S. Environmental Protection Agency National Fish Tissue Study (2003) data were used to determine the most significant predictors of toxicity equivalents with multiple regression analysis. The strongest predictive model (P < 0.0001, R2 = 0.97) included five compounds (PCB-118; PCB-126; 2,3,7,8-TCDD; 1,2,3,6,7,8-HxCDD; 2,3,4,7,8-PeCDF). However, the required lower limit of detection for an analytical method measuring these congeners is 0.1 ppt and would not provide much benefit over the current analytical method. An alternative model (P < 0.0001, R2 = 0.68) that included three PCBs (PCB-138, PCB-153, PCB-118) would require a limit of detection of 1,000 ppt and be more practical. This research demonstrates that the measurement of selected compounds can be used to estimate toxicity equivalents and consequently serve as the impetus for the development of lower cost, rapid analytical methods for analysis of fish.


Subject(s)
Fishes/metabolism , Food Contamination/analysis , Seafood/analysis , Water Pollutants, Chemical/analysis , Animals , Body Burden , Consumer Product Safety , Dioxins/analysis , Furans/analysis , Humans , Pesticide Residues/analysis , Polychlorinated Biphenyls/analysis , Predictive Value of Tests
15.
Lancet ; 362(9401): 2052-8, 2003 Dec 20.
Article in English | MEDLINE | ID: mdl-14697804

ABSTRACT

BACKGROUND: Vitamin A deficiency adversely affects child morbidity and survival. This deficiency is estimated by measurement of plasma retinol concentrations, but because plasma retinol is reduced by clinical and subclinical infection, this proxy measure can lead to overestimation. Infection and trauma are accompanied by rises in concentrations of acute-phase proteins in plasma. We aimed to estimate vitamin A deficiency more accurately by measuring changes in plasma retinol and acute-phase proteins associated with subclinical infection or convalescence. METHODS: We analysed data for concentrations of plasma retinol and one or more acute-phase proteins (alpha1-acid-glycoprotein, alpha1-antichymotrypsin, C-reactive protein, or serum amyloid A) from 15 studies of apparently healthy individuals. We generated summary estimates of differences in retinol concentrations for incubation, early, and late convalescent phases of infection between people with none and those with one or more raised acute-phase proteins. We compared these groups in two, three, and four group analyses. We also compared a subgroup of apparently healthy preschool (1-5 years) children with results from all other studies. FINDINGS: For all four proteins, retinol values were much higher in people with normal concentrations of protein, than in individuals with raised concentrations (16% higher for alpha1-antichymotrypsin, 18% for alpha1-acid-glycoprotein, 25% for C-reactive protein, and 32% for serum amyloid A). Estimates of the reduction in plasma retinol for individuals with infection compared with healthy individuals, were 13% (incubation), 24% (early convalescent), and 11% (late convalescent). Estimates of vitamin A deficiency in individuals with no raised acute-phase proteins (healthy group) were much the same as those obtained by adjustment of plasma retinol concentrations in the whole group using acute-phase proteins. INTERPRETATION: We recommend that surveys to estimate vitamin A deficiency should include measurements of serum C-reactive protein and alpha1-acid-glycoprotein concentrations. Information about acute-phase proteins will enable plasma retinol concentrations to be corrected where sub-clinical infection exists, and the healthy sub-group to be identified.


Subject(s)
Infections/blood , Vitamin A Deficiency/epidemiology , Vitamin A/blood , Acute-Phase Proteins/analysis , Apolipoproteins/blood , C-Reactive Protein/analysis , Child, Preschool , Comorbidity , Convalescence , Humans , Infant , Infections/epidemiology , Orosomucoid/analysis , Prevalence , Serum Amyloid A Protein , Vitamin A Deficiency/blood , alpha 1-Antichymotrypsin/blood
16.
Bone ; 32(5): 546-53, 2003 May.
Article in English | MEDLINE | ID: mdl-12753871

ABSTRACT

Achievement of higher peak bone mass early in life may play a critical role against postmenopausal bone loss. Bone mineral density (BMD) of the spine, femoral neck, greater trochanter, Ward's triangle, and spine bone mineral content (BMC) and bone surface area (BSA) were assessed by dual energy x-ray absorptiometry in 300 healthy females (age 6-32 years). Bone measurements were described by using nonlinear models with age, weight, height, or dietary calcium intake as the explanatory variables. At the spine, femoral neck, greater trochanter, and Ward's triangle, the highest BMD level was observed at 23.0 +/- 1.4, 18.5 +/- 1.6, 14.2 +/- 2.0, and 15.8 +/- 2.1 years, respectively. The age of attaining peak spine BMC and BSA cannot be estimated, as significant increases in these two measures were observed through this age group. Age, weight, and height were all significant predictors of all these bone measurements. Weight was a stronger predictor than age for all sites. Dietary calcium intake was not a significant predictor for any of these bone measurements. We conclude that age of attaining peak bone mass at the hip is younger than at the spine, and BMC and BSA at the spine continue to increase through the early thirties in females.


Subject(s)
Bone Density , Femur Neck/chemistry , Osteoporosis, Postmenopausal/prevention & control , Spine/chemistry , Adolescent , Adult , Age Factors , Body Weight , Calcium, Dietary/therapeutic use , Female , Humans , Models, Biological
17.
J Clin Endocrinol Metab ; 88(3): 1043-7, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12629083

ABSTRACT

Blacks develop a higher peak bone mass than whites which is associated with a reduced risk for bone fracture. The physiological basis for the difference in bone mass was investigated by metabolic balance and calcium kinetic studies in adolescent black and white girls. The hypothesis that the greater peak bone mass in blacks compared with whites is due to suppressed bone resorption was tested. Subjects were housed in a supervised environment for 3 wk during which time they consumed a controlled diet and collected all excreta. Subjects were given stable calcium isotopes orally and intravenously after 1 wk adaptation. Blacks have greater calcium retention (mean +/- SD, 11.5 +/- 6.1 vs. 7.3 +/- 4.1 mmol/d, P < 0.05) consistent with greater bone formation rates (49.4 +/- 13.5 vs. 36.5 +/- 13.6 mmol/d, P < 0.05) relative to bone resorption rates (37.4 +/- 13.2 vs. 29.4 +/- 10.9 mmol/d, P = 0.07), increased calcium absorption efficiency (54 +/- 19 vs. 38 +/- 18%, P < 0.05) and decreased urinary calcium (1.15 +/- 0.95 vs. 2.50 +/- 1.35 mmol/d, P < 0.001), compared with whites. The racial differences in calcium retention in adolescence can account for the racial differences in bone mass of adults.


Subject(s)
Bone Density , Bone Remodeling/physiology , Bone Resorption/ethnology , Calcium/metabolism , Adolescent , Black People , Female , Humans , Osteogenesis/physiology , White People
18.
Med Sci Sports Exerc ; 33(6): 873-80, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11404650

ABSTRACT

PURPOSE: The effect of quantified resistance and high impact exercise training on bone mass as modified by age and oral contraceptive (OCont) use in young women was studied. METHODS: Women were categorized by age (18-23 vs 24-31 yr) and OCont use, and were then randomized into either three sessions of resistance exercise plus 60 min.wk-1 of jumping rope or a control group for 24 months. Total body, spine, femoral neck, greater trochanter, Ward's area, and radial bone mineral density (BMD) and/or content (BMC), biochemical markers of bone turnover, dietary intake of calcium, lean body mass, maximal oxygen uptake, and strength were determined at baseline and every 6 months. RESULTS: Total body (TB) BMC percent change from baseline was higher in exercisers compared with nonexercisers at 6 and 24 months. OCont users had lower bone turnover at baseline and a decrease in TBBMC from baseline compared with non-OCont users at 24 months. Spine BMC and BMD decreased in the exercise and OCont group at 6 months and remained significantly below nonexercisers who used oral contraceptives at 2 yr. Femoral neck BMD also decreased in the exercise and oral contraceptive group at 6 months. CONCLUSIONS: Exercise prevented a decline in TBBMC seen in the nonexercisers. On the other hand, exercise in oral contraceptive users prevented the increase observed in the spine of the nonexercise plus OCont group.


Subject(s)
Bone Density , Contraceptives, Oral/adverse effects , Exercise , Adolescent , Adult , Biomarkers/analysis , Female , Health Status , Humans , Weight Lifting
19.
J Am Coll Nutr ; 19(6): 754-60, 2000.
Article in English | MEDLINE | ID: mdl-11194528

ABSTRACT

OBJECTIVE: Relationships between micronutrients and dairy product intake and changes in body weight and composition over two years were investigated. DESIGN: Two year prospective non-concurrent analysis of the effect of calcium intake on changes in body composition during a two year exercise intervention. SUBJECTS: 54 normal weight young women, 18 to 31 years of age. MEASURES OF OUTCOME: Mean intakes of nutrients of interest were determined from three-day diet records completed at baseline and every six months for two years. The change in total body weight and body composition (assessed by dual x-ray absorptiometry) from baseline to two years was also determined. RESULTS: Total calcium/kilocalories and vitamin A together predicted (negatively and positively, respectively) changes in body weight (R2 = 0.19) and body fat (R2 = 0.27). Further, there was an interaction of calcium and energy intake in predicting changes in body weight, such that, only at lower energy intakes, calcium intake (not adjusted for energy) predicted changes in body weight. CONCLUSIONS: Regardless of exercise group assignment, calcium adjusted for energy intake had a negative relationship and vitamin A intake a positive relationship with two year changes in total body weight and body fat in young women aged 18 to 31 years. Thus, subjects with high calcium intake, corrected by total energy intake, and lower vitamin A intake gained less weight and body fat over two years in this randomized exercise intervention trial.


Subject(s)
Adipose Tissue/physiology , Body Composition/physiology , Calcium, Dietary/administration & dosage , Exercise , Absorptiometry, Photon , Adipose Tissue/drug effects , Adolescent , Adult , Body Composition/drug effects , Body Weight , Calcium, Dietary/pharmacology , Dairy Products , Diet Records , Female , Humans , Obesity/prevention & control , Prospective Studies , Vitamin A/administration & dosage , Vitamin A/pharmacology
20.
Int J Epidemiol ; 28(1): 169-74, 1999 Feb.
Article in English | MEDLINE | ID: mdl-10195684

ABSTRACT

BACKGROUND: Intestinal parasitism is common among children in developing countries, but the risk factors for infection are not well characterized. METHODS: A stool examination was performed on 286 randomly selected children aged 1-18 years from three rural villages in Guinea, Africa. Information collected by questionnaire was used to examine the relationship between geophagia and infection with intestinal nematodes acquired by ingestion versus skin penetration. RESULTS: Fifty-three per cent of children were infected by at least one type of soil-transmitted nematode. Geophagia was reported by parents to occur in 57%, 53%, and 43%, of children ages 1-5, 6-10, and 11-18 years, respectively. The pattern of geophagia by age and gender of the children more closely resembled the infection pattern for the two orally acquired and soil-transmitted nematodes (Ascaris lumbricoides, Trichuris trichiura) than it did the infection pattern for the two soil-transmitted nematodes that infect by skin penetration (hookworm, Strongyloides stercoralis). CONCLUSIONS: These findings demonstrate that geophagia is an important risk factor for orally acquired nematode infections in African children. Education regarding geophagia prevention should be an integral component of any soil-transmitted parasite control programme.


PIP: Intestinal parasites are routinely found among children in developing countries, but the risk factors of such infection are poorly characterized. The stools of 286 randomly selected children aged 1-18 years from 3 rural villages in Guinea were examined. Data collected via questionnaire were then analyzed to assess the relationship between geophagia, the regular ingestion of soil, and infection with intestinal nematodes acquired through ingestion rather than through skin penetration. 53% of children were infected with at least 1 type of soil-transmitted nematode, and geophagia was reported by parents to occur in 57%, 53%, and 43% of children aged 1-5, 6-10, and 11-18 years, respectively. The pattern of geophagia by age and gender of the children more closely resembled the infection pattern for the 2 orally acquired and soil-transmitted nematodes Ascaris lumbricoides and Trichuris trichiura than it did the infection pattern for the 2 soil-transmitted nematodes which infect by penetrating the skin, hookworm and Strongyloides stercoralis. Geophagia is therefore an important risk factor for orally acquired nematode infections among African children, and education on geophagia prevention should be an integral component of all soil-transmitted parasite control programs.


Subject(s)
Intestinal Diseases, Parasitic/epidemiology , Nematode Infections/epidemiology , Pica/epidemiology , Rural Population/statistics & numerical data , Soil/parasitology , Adolescent , Child , Child, Preschool , Female , Guinea/epidemiology , Humans , Infant , Intestinal Diseases, Parasitic/parasitology , Logistic Models , Male , Nematode Infections/parasitology , Pica/parasitology , Prevalence
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