Munro Peacock

Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, United States

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Publications (107)831.01 Total impact

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    ABSTRACT: Context: Citrus fruits contain unique flavanones. One of the most abundant of the flavanones, hesperidin, has been shown to prevent bone loss in ovariectomized rats. Objective: The objective of the study was to measure the effect of hesperidin with or without calcium supplementation on bone calcium retention in postmenopausal women. Design: The study was a double blind, placebo-controlled, randomized order cross-over design of 500 g hesperidin with or without 500 mg calcium supplement in 12 healthy postmenopausal women. Bone calcium retention was determined from urinary excretion of the rare isotope, (41)Ca, from bone. Results: Calcium plus hesperidin, but not hesperidin alone, improved bone calcium retention by 5.5% (p < 0.04). Conclusion: Calcium supplementation (Calcilock®), in combination with hesperidin, is effective at preserving bone in postmenopausal women.
    No preview · Article · Jan 2016 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: A genome-wide association study was performed on 1130 premenopausal women to detect common variants associated with three serum iron-related phenotypes. Total iron binding capacity was strongly associated (p = 10− 14) with variants in and near the TF gene (transferrin), the serum iron transporting protein, and with variants in HFE (p = 4 × 10− 7), which encodes the human hemochromatosis gene. Association was also detected between percent iron saturation (p = 10− 8) and variants in the chromosome 6 region containing both HFE and SLC17A2, which encodes a phosphate transport protein. No significant associations were detected with serum iron, but variants in HFE were suggestive (p = 10− 6). Our results corroborate prior studies in older subjects and demonstrate that the association of these genetic variants with iron phenotypes can be detected in premenopausal women.
    No preview · Article · Dec 2015 · Blood Cells Molecules and Diseases
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    ABSTRACT: Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway.
    No preview · Article · Nov 2015 · Breast Cancer Research and Treatment
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    ABSTRACT: Background: Research indicates that plasma 25-hydroxyvitamin D [25(OH)D] is associated with insulin resistance, but whether regional adiposity confounds this association is unclear. Objective: This study sought to assess the potential influence of adiposity and its anatomical distribution on the relation between plasma 25(OH)D and insulin resistance. Methods: A secondary analysis of data from middle-aged overweight and obese healthy adults [n = 336: 213 women and 123 men; mean ± SD (range); age: 48 ± 8 y (35-65 y); body mass index (BMI): 30.3 ± 2.7 kg/m(2) (26-35 kg/m(2))] from West Lafayette, IN (40.4°N), were used for this cross-sectional analysis. Multiple linear regression analyses that controlled for multiple covariates were used as the primary statistical model. Results: Of all participants, 8.6% and 20.5% displayed moderate [20.1-37.5 nmol/L plasma 25(OH)D] to mild (37.6-49.9 nmol/L) vitamin D insufficiency, respectively. A regression analysis controlling for age, sex, race, plasma parathyroid hormone level, seasons of year, and supplement use showed that 25(OH)D was negatively associated with fasting insulin (P = 0.021). Additional regression analyses showed that total and central adiposity but not peripheral adiposity predicted low plasma 25(OH)D [total fat mass index (FMI): P = 0.018; android FMI: P = 0.052; gynoid FMI: P = 0.15; appendicular FMI: P = 0.07) and insulin resistance (homeostasis model assessment of insulin resistance: total and android FMI, P <0.0001; gynoid FMI, P = 0.94; appendicular FMI, P = 0.86). The association of total and central adiposity with insulin resistance remained significant after adjusting for plasma 25(OH)D. However, adjusting for central adiposity but not other anatomical measures of fat distribution eliminated the association between plasma 25(OH)D and insulin resistance. Conclusion: Central adiposity drives the association between plasma 25(OH)D and insulin resistance in overweight and obese adults. The trial was registered at clinicaltrials.gov as NCT00812409.
    No preview · Article · Oct 2015 · Journal of Nutrition
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    ABSTRACT: Postmenopausal estrogen depletion is a major contributing factor to bone loss. Soy isoflavones have variable effects on the prevention of postmenopausal bone loss, which is possibly related to the specific isoflavone content or the variable equol-producing capacity of individuals. We aimed to determine the effects of the content of isoflavones in a soy supplement and the equol-producing ability of the individual on postmenopausal bone calcium retention. The study was a blinded, randomized, crossover intervention trial in 24 postmenopausal women who were prescreened for their ability to convert daidzein to equol. Women were equilibrated with (41)Ca before the intervention. Interventions were 5 soy isoflavone oral supplements (2 doses of a genistein-rich soy supplement and 3 doses of mixed isoflavones in various proportions) and a bisphosphonate (risedronate). Each intervention was given sequentially for 50 d followed by a 50-d washout period. The percentage of bone calcium retention was determined from the change in urinary (41)Ca:calcium. Interventions that ranged from 52 to 220 mg total isoflavones/d increased bone calcium retention between 3.4% and 7.6% (P < 0.05), which was a moderate effect compared with that of risedronate at 15.3% (95% CI: 7.1, 22.7; P = 0.0014). The most-effective soy intervention delivered 105.23 mg total isoflavones/d as genistein, daidzein, and glycitein in their natural ratios and increased bone calcium retention by 7.6% (95% CI: 4.9%, 10.2%; P < 0.0001). Genistein, at 52.85 mg/d, increased bone calcium retention by 3.4% (95% CI: 0.5%, 6.2%; P = 0.029); but there was no benefit at higher amounts (113.52 mg/d). There was no difference (P = 0.5) in bone calcium retention between equol producers and nonproducers. Soy isoflavones, although not as potent as risedronate, are effective bone-preserving agents in postmenopausal women regardless of their equol-producing status, and mixed isoflavones in their natural ratios are more effective than enriched genistein. This trial was registered at clinicaltrials.gov as NCT00244907. © 2015 American Society for Nutrition.
    No preview · Article · Aug 2015 · American Journal of Clinical Nutrition
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    ABSTRACT: In XLH, serum fibroblast growth factor 23 (FGF23) is increased and results in reduced renal maximum threshold for phosphate reabsorption (TmP), reduced serum inorganic phosphorus (Pi) and inappropriately low normal serum 1,25 dihydroxyvitamin D([1,25(OH)2 D) concentration, with subsequent development of rickets or osteomalacia. KRN23 is a recombinant human IgG1 monoclonal antibody which binds to FGF23 and blocks its activity. Up to 4 doses of KRN23 were administered subcutaneously every 28 days to 28 adults with XLH. Mean (Standard Deviation) KRN23 doses administered were: 0.05, 0.10 ± 0.01, 0.28 ± 0.06, and 0.48 ± 0.16 mg/kg. The mean time to reach maximum serum KRN23 levels was 7.0 to 8.5 days. The mean KRN23 half-life was 16.4 days. The mean area under the concentration-time curve (AUCn ) for each dosing interval increased proportionally with increases in KRN23 dose. The mean inter-subject variability in AUCn ranged from 30% to 37%. The area under the effect concentration-time curve (AUECn ) for change from baseline in TmP/GFR, serum Pi,1, 25(OH)2 D and bone markers for each dosing interval increased linearly with increases in KRN23AUCn . Linear correlation between serum KRN23 concentrations and increase in serum Pi support KRN23 dose adjustments based on pre-dose serum Pi concentration. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jun 2015 · The Journal of Clinical Pharmacology
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    ABSTRACT: In X-linked hypophosphatemia (XLH), elevated fibroblast growth factor 23 (FGF23) decreases the maximum rate of renal phosphate reabsorption (TmP/GFR) and serum phosphorus (Pi), resulting in rickets and/or osteomalacia. To test the hypothesis that monthly KRN23 (anti-FGF23 antibody) would safely improve serum Pi in adults with XLH. Two sequential open-label Phase 1/2 studies. Six academic medical centers. Twenty-eight adults with XLH participated in a 4-month dose-escalation study (0.05-0.6 mg/kg); 22 entered a 12-month extension study (0.1-1 mg/kg). KRN23 was injected subcutaneously every 28 days. The proportion attaining normal serum Pi and safety. At baseline, mean TmP/GFR, serum Pi, and 1,25(OH)2D were 1.6±0.4mg/dL, 1.9±0.3mg/dL and 37±14pg/mL, respectively. During dose-escalation, TmP/GFR, Pi, and 1,25(OH)2D increased, peaking at 7 days for TmP/GFR and Pi, and at 3-7 days for 1,25(OH)2D; remaining above (TmP/GFR, Pi) or near [1,25(OH)2D] pre-dose levels at trough. After each of the 4 escalating doses, peak Pi was between 2.5 and 4.5mg/dL in 14.8%, 37.0%, 74.1%, and 88.5% of subjects respectively. During the 12-month extension, peak Pi was in the normal range for 57.9-85.0% of subjects, and ≥25% maintained trough Pi levels within the normal range. Serum Pi did not exceed 4.5mg/dL in any subject. Although 1,25(OH)2D levels increased transiently, mean serum and urinary calcium remained normal. KRN23 treatment increased biomarkers of skeletal turnover, and had a favorable safety profile. Monthly KRN23 significantly increased serum Pi, TmP/GFR, and 1,25(OH)2D in all subjects. KRN23 has potential for effectively treating XLH.
    No preview · Article · Apr 2015 · The Journal of Clinical Endocrinology and Metabolism
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    ABSTRACT: Ferritin, a 24-mer heteropolymer of heavy (H) and light (L) subunits, is the main cellular iron storage protein and plays a pivotal role in iron homeostasis by modulating free iron levels thus reducing radical-mediated damage. The H subunit has ferroxidase activity (converting Fe(II) to Fe(III)), while the L subunit promotes iron nucleation and increases ferritin stability. Previous studies on the H gene (Fth) in mice have shown that complete inactivation of Fth is lethal during embryonic development, without ability to compensate by the L subunit. In humans, homozygous loss of the L gene (FTL) is associated with generalized seizure and atypical restless leg syndrome, while mutations in FTL cause a form of neurodegeneration with brain iron accumulation. Here we generated mice with genetic ablation of the Fth and Ftl genes. As previously reported, homozygous loss of the Fth allele on a wild-type Ftl background was embryonic lethal, whereas knock-out of the Ftl allele (Ftl-/-) led to a significant decrease in the percentage of Ftl-/- newborn mice. Analysis of Ftl-/- mice revealed systemic and brain iron dyshomeostasis, without any noticeable signs of neurodegeneration. Our findings indicate that expression of the H subunit can rescue the loss of the L subunit and that H ferritin homopolymers have the capacity to sequester iron in vivo. We also observed that a single allele expressing the H subunit is not sufficient for survival when both alleles encoding the L subunit are absent, suggesting the need of some degree of complementation between the subunits as well as a dosage effect.
    Full-text · Article · Jan 2015 · PLoS ONE
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    ABSTRACT: Conclusions: 1) There are limited new data available on the natural history of asymptomatic PHPT. Although recognition of normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism) is increasing, data on the clinical presentation and natural history of this phenotypeare limited. 2) Although there are geographic differences in the predominant phenotypes of PHPT (symptomatic, asymptomatic, normocalcemic), they do not justify geography-specific management guidelines. 3) Recent data using newer, higher resolution imaging and analytic methods have revealed that in asymptomatic PHPT, both trabecular bone and cortical bone are affected. 4) Clinically silent nephrolithiasis and nephrocalcinosis can be detected by renal imaging and should be listed as a new criterion for surgery. 5) Current data do not support a cardiovascular evaluation or surgery forthe purpose of improving cardiovascular markers, anatomical orfunctional abnormalities. 6) Some patients with mild PHPT have neuropsychological complaints and cognitive abnormalities, and some of these patients may benefit from surgical intervention. However, it is not possible at this time to predict which patients with neuropsychological complaints or cognitive issues will improve after successful parathyroid surgery.
    Full-text · Article · Aug 2014 · Journal of Clinical Endocrinology & Metabolism
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    ABSTRACT: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
    Full-text · Article · Jul 2014 · Nature
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    ABSTRACT: Mexican Americans are an understudied ethnic group for determinants of bone health, although the risk of age-related osteoporosis is high in this rapidly growing sector of the U.S. population. Thus, the objective of the present study was to establish the dietary calcium requirements for bone health in Mexican-American adolescents by measuring calcium retention calculated from balance in response to a range of dietary calcium intakes and to determine predictors of skeletal calcium retention. Adolescents aged 12-15 y were studied twice on paired calcium intakes ranging from 600 to 2300 mg/d using randomized-order, crossover 3-wk balance studies. Skeletal calcium retention was calculated as dietary calcium intake minus calcium excreted in feces and urine over the last 2 wk of balance. A linear model was developed to explain the variation on calcium retention. Boys (n = 20) were taller and had higher lean mass, usual dietary calcium intake, bone mineral content, and serum alkaline phosphatase compared with girls, whereas girls (n = 20) had higher Tanner scores and greater fat mass. Calcium retention increased with calcium intake (P < 0.0001) and did not differ by sex (P = 0.66). In boys and girls considered together, calcium intake explained 33% of the variation in calcium retention. Serum alkaline phosphatase explained an additional 11% of the variation in calcium retention. Other variables measured, including urine N-telopeptide of type I collagen/creatinine ratio, Tanner score, serum parathyroid hormone and 25-hydroxyvitamin D, weight, height, and body mass index, did not contribute to the variance in calcium retention. In adolescence, calcium retention in both Mexican-American boys and girls was higher than studied previously in adolescent nonHispanic white girls. This trial was registered at clinicaltrials.gov as NCT01277185.
    Full-text · Article · May 2014 · Journal of Nutrition
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    ABSTRACT: Soluble maize fibre (SCF) has been found to significantly improve bone mineral density and strength in growing rats compared with several other novel prebiotic fibres. The objective of the present study was to investigate the effect of SCF on Ca absorption and retention in pubertal children by studying the potential absorption mechanisms of the intestinal microbiota. A total of twenty-four adolescent boys and girls (12–15 years) participated in two 3-week metabolic balance studies testing 0 g/d SCF (control (CON) treatment) and 12 g/d SCF (SCF treatment) in a random order by inclusion in a low-Ca diet (600 mg/d). Fractional Ca absorption was measured at the end of the two intervention periods using a dual-stable isotope method. Diet composites and faecal and urine samples were collected daily and analysed for Ca content. Ca retention was calculated as dietary Ca intake minus Ca excretion in faeces and urine over the last 2 weeks. Microbial community composition in the faecal samples collected at the beginning and end of each session was determined by 454 pyrosequencing of the PCR-amplified 16S ribosomal RNA gene. Fractional Ca absorption was 12 % higher (41 mg/d) after the SCF treatment compared with that after the CON treatment (0·664 ( sd 0·129) and 0·595 ( sd 0·142), respectively; P = 0·02), but Ca retention was unaffected. The average proportion of bacteria of the phylum Bacteroidetes was significantly greater in the participants after the SCF treatment than after the CON treatment. These results suggest that moderate daily intake of SCF, a well-tolerated prebiotic fibre, increases short-term Ca absorption in adolescents consuming less than the recommended amounts of Ca.
    Preview · Article · May 2014 · British Journal Of Nutrition
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    ABSTRACT: Osteoporosis is a common complex disorder with reduced bone mineral density (BMD) and increased susceptibility to fracture. Peak BMD is one of the primary determinants of osteoporotic fracture risk, and is under substantial genetic control. Extracellular matrix, a major component of bone, influences BMD by regulating mineral deposition and maintaining cellular activity. It contains several SIBLING family proteins, null mutations of which cause mineralization defects in humans. In this study, we tested 59 single-nucleotide polymorphisms (SNPs) located in the 5 SIBLING family genes (DSPP, DMP1, IBSP, MEPE and SPP1) for association with normal variation in peak BMD in healthy men and women. We measured femoral neck (FN) and lumbar spine (LS) areal BMD by dual energy x-ray absorptiometry (DXA) in 1,692 premenopausal European-American women, 512 premenopausal African-American women and 715 European-American men. SNPs were tested for association with FN and LS BMD in the 3 subsamples. In the European-American women, we observed association (p≤0.005) with LS-BMD for SNPs in DSPP, IBSP and MEPE, and for FN-BMD with SNPs in DMP1 and IBSP. Allele specific regulation of gene expression (ASE) is an important mechanism in which an allele giving rise to modest influence in transcript abundance might result in a predisposition to disease. To identify whether there was ASE of SIBLING family genes at these SNPs, we examined 52 human bone samples obtained from the femoral neck during surgical hip replacement (27 female, 25 male; 44 European-American and 8 African-American). We observed unidirectional ASE for the IBSP gene, with lower expression of the G allele compared to the A allele for SNP rs17013181. Our data suggest that SNPs within the SIBLING genes may contribute to normal variation of peak BMD. Further studies are necessary to identify the functional variants and to determine the mechanisms underlying the differences in ASE and how these differences relate to the pathophysiology of osteoporosis.
    No preview · Article · Apr 2014 · Bone
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    ABSTRACT: Background: X-linked hypophosphatemia (XLH) is the most common heritable form of rickets and osteomalacia. XLH-associated mutations in phosphate-regulating endopeptidase (PHEX) result in elevated serum FGF23, decreased renal phosphate reabsorption, and low serum concentrations of phosphate (inorganic phosphorus, Pi) and 1,25-dihydroxyvitamin D [1,25(OH)2D]. KRN23 is a human anti-FGF23 antibody developed as a potential treatment for XLH. Here, we have assessed the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of KRN23 following a single i.v. or s.c. dose of KRN23 in adults with XLH. Methods: Thirty-eight XLH patients were randomized to receive a single dose of KRN23 (0.003-0.3 mg/kg i.v. or 0.1-1 mg/kg s.c.) or placebo. PK, PD, immunogenicity, safety, and tolerability were assessed for up to 50 days. Results: KRN23 significantly increased the maximum renal tubular threshold for phosphate reabsorption (TmP/GFR), serum Pi, and 1,25(OH)2D compared with that of placebo (P<0.01). The maximum serum Pi concentration occurred later following s.c. dosing (8-15 days) compared with that seen with i.v. dosing (0.5-4 days). The effect duration was dose related and persisted longer in patients who received s.c. administration. Changes from baseline in TmP/GFR, serum Pi, and serum 1,25(OH)2D correlated with serum KRN23 concentrations. The mean t1/2 of KRN23 was 8-12 days after i.v. administration and 13-19 days after s.c. administration. Patients did not exhibit increased nephrocalcinosis or develop hypercalciuria, hypercalcemia, anti-KRN23 antibodies, or elevated serum parathyroid hormone (PTH) or creatinine. Conclusion: KRN23 increased TmP/GFR, serum Pi, and serum 1,25(OH)2D. The positive effect of KR23 on serum Pi and its favorable safety profile suggest utility for KRN23 in XLH patients. Trial registration. Clinicaltrials.gov NCT00830674. Funding. Kyowa Hakko Kirin Pharma, Inc.
    Preview · Article · Feb 2014 · The Journal of clinical investigation
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    ABSTRACT: FGF23 gain of function mutations can lead to autosomal dominant hypophosphatemic rickets (ADHR) disease onset at birth, or delayed onset following puberty or pregnancy. We previously demonstrated that the combination of iron deficiency and a knock-in R176Q FGF23 mutation in mature mice induced FGF23 expression and hypophosphatemia that paralleled the late onset ADHR phenotype. As anemia in pregnancy and in premature infants is common, the goal of this study was to test whether iron deficiency alters phosphate handling in neonatal life. Wild type (WT) and ADHR female breeder mice were provided control or iron-deficient diets during pregnancy and nursing. Iron-deficient breeders were also made iron replete. Iron deficient WT and ADHR pups were hypophosphatemic, with ADHR pups having significantly lower serum phosphate (P < 0.01) and widened growth plates. Both genotypes increased bone FGF23 mRNA (>50 fold; P < 0.01). WT and ADHR pups receiving low iron had elevated intact serum FGF23 with ADHR mice affected to a greater degree (P < 0.01). Iron deficient mice also showed increased Cyp24a1 and reduced Cyp27b1, and low serum 1,25(OH)2 vitamin D. Iron repletion normalized most abnormalities. Because iron deficiency can induce tissue hypoxia, oxygen deprivation was tested as a regulator of FGF23, and was shown to stimulate FGF23 mRNA in vitro and serum C-terminal FGF23 in normal rats in vivo. These studies demonstrate that FGF23 is modulated by iron status in young WT and ADHR mice and that hypoxia independently controls FGF23 expression in situations of normal iron. Therefore, disturbed iron and oxygen metabolism in neonatal life may have important effects on skeletal function and structure through FGF23 activity on phosphate regulation.
    Full-text · Article · Feb 2014 · Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research

  • No preview · Conference Paper · Feb 2014
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    ABSTRACT: Osteoporosis is a common complex disorder with reduced bone mineral density (BMD) and increased susceptibility to fracture. Peak BMD is one of the primary determinants of osteoporotic fracture risk, and is under substantial genetic control. Extracellular matrix, a major component of bone, influences BMD by regulating mineral deposition and maintaining cellular activity. It contains several SIBLING family proteins, null mutations of which cause mineralization defects in humans. In this study, we tested 59 single-nucleotide polymorphisms (SNPs) located in the 5 SIBLING family genes (DSPP, DMP1, IBSP, MEPE and SPP1) for association with normal variation in peak BMD in healthy men and women. We measured femoral neck (FN) and lumbar spine (LS) areal BMD by dual energy x-ray absorptiometry (DXA) in 1,692 premenopausal European-American women, 512 premenopausal African-American women and 715 European-American men. SNPs were tested for association with FN and LS BMD in the 3 subsamples. In the European-American women, we observed association (p ≤ 0.005) with LS-BMD for SNPs in DSPP, IBSP and MEPE, and for FN-BMD with SNPs in DMP1 and IBSP. Allele specific regulation of gene expression (ASE) is an important mechanism in which an allele giving rise to modest influence in transcript abundance might result in a predisposition to disease. To identify whether there was ASE of SIBLING family genes at these SNPs, we examined 52 human bone samples obtained from the femoral neck during surgical hip replacement (27 female, 25 male; 44 European-American and 8 African-American). We observed unidirectional ASE for the IBSP gene, with lower expression of the G allele compared to the A allele for SNP rs17013181. Our data suggest that SNPs within the SIBLING genes may contribute to normal variation of peak BMD. Further studies are necessary to identify the functional variants and to determine the mechanisms underlying the differences in ASE and how these differences relate to the pathophysiology of osteoporosis.
    No preview · Article · Jan 2014 · Bone
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    ABSTRACT: We assessed the influence of serum 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone (PTH) concentrations on oral glucose tolerance, body composition, and muscle strength in older, nondiabetic adults who performed resistance exercise training (RT) while consuming diets with either 0.9 or 1.2 g protein kg(-1) d(-1). We hypothesized that individuals with insufficient 25(OH)D and/or high PTH would have less improvement in glucose tolerance after 12 weeks of RT compared with individuals with sufficient 25(OH)D and lower PTH. Sixteen men and 19 women (aged 61 ± 8 years; range, 50-80 years; body mass index, 26.3 ± 3.6 kg/m(2)) performed RT 3 times/wk for 12 weeks, with oral glucose tolerance tests done at baseline and postintervention. Protein intake did not influence the responses described below. Plasma glucose area under the curve (P = .02) and 2-hour plasma glucose concentration (P = .03) were higher for vitamin D-insufficient subjects (25[OH]D <50 nmol/L, n = 7) vs vitamin D-sufficient subjects (25[OH]D ≥50 nmol/L, n = 28). These differences remained significant after adjustment for age and body mass index. Resistance exercise training reduced fat mass (mean ± SD, -6% ± 7%; P < .001) and increased lean body mass (2% ± 3%, P < .001) and whole-body muscle strength (32% ± 17%, P < .001) in these weight-stable subjects but did not affect 25(OH)D or PTH concentrations. Oral glucose tolerance improved after RT (-10% ± 16% in glucose area under the curve and -21% ± 40% in 2-hour glucose, P = .001), but baseline 25(OH)D and PTH did not influence these RT-induced changes. These findings indicate that vitamin D status and RT independently affect glucose tolerance, and a training-induced improvement in glucose tolerance does not offset the negative effect of insufficient vitamin D status in older, nondiabetic adults.
    Full-text · Article · May 2013 · Nutrition research
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    ABSTRACT: Oncogenic osteomalacia is a rare paraneoplastic syndrome induced by mesenchymal tumors. Just over 100 cases have been reported for this rare disorder, and only seven instances were caused by phosphaturic mesenchymal tumors of the spine. The authors present an illustrative case of a 61-year-old woman with oncogenic osteomalacia induced by a tumor of the spine, and review the literature describing the clinical presentation, surgical treatment, and follow-up of this syndrome.
    Full-text · Article · Apr 2013 · Journal of Clinical Neuroscience
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    ABSTRACT: BACKGROUND: Previously, we showed that black girls retained more calcium than white girls did and that salt loading negatively affected calcium retention. Racial differences likely exist in other bone minerals also, such as magnesium, in response to salt loading during growth. OBJECTIVE: We studied racial differences in magnesium metabolism in response to dietary sodium and calcium during rapid bone growth. DESIGN: Twenty-seven white and 40 black girls (11-15 y old) were studied for 3 wk while they consumed low-sodium (1.3 g/d) and high-sodium (3.8 g/d) diets by using a randomized-order, crossover metabolic study with 3 dietary calcium intakes; the magnesium dietary intake was fixed at 230 mg/d. Urine and feces were collected during each 3-wk period in 24-h pools and analyzed for magnesium. A mixed-model ANOVA was used to determine the effect of race and dietary sodium with calcium intake as a covariate. RESULTS: Salt loading or calcium intake had no significant effect on urinary magnesium excretion. Blacks excreted significantly less urinary magnesium (mean ± SD: 83.8 ± 25.6 mg/d) than did whites (94.9 ± 27.3 mg/d; P < 0.05). No effects were observed in fecal magnesium excretion. Magnesium retention was higher with the low-sodium diet (50.1 ± 44.0 mg/d) than with the high-sodium diet (39.3 ± 49.8 mg/d (P < 0.05), with no effects of race or calcium intake. Salt loading had no effect on biomarkers. Whites had higher 25-hydroxyvitamin D and insulin-like growth factor binding protein 3 but lower 1,25-dihydroxyvitamin D and parathyroid hormone concentrations. CONCLUSIONS: Blacks excreted less urinary magnesium than did whites. Magnesium retention was similar between races but higher with the low-sodium diet. Kinetic studies are needed to fully explain magnesium homeostasis. This trial was registered at clinicaltrials.gov as NCT01564238.
    Full-text · Article · Apr 2013 · American Journal of Clinical Nutrition

Publication Stats

8k Citations
831.01 Total Impact Points

Institutions

  • 1992-2015
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, Indiana, United States
  • 1989-2015
    • Indiana University School of Medicine
      • • Division of Endocrinology and Metabolism
      • • Department of Medicine
      Indianapolis, Indiana, United States
  • 2010
    • Indianapolis Zoo
      Indianapolis, Indiana, United States
    • Wellcome Trust Sanger Institute
      Cambridge, England, United Kingdom
  • 2004-2010
    • Purdue University
      • Department of Statistics
      West Lafayette, Indiana, United States
  • 2005-2009
    • Indiana University Bloomington
      • School of Medicine
      Bloomington, Indiana, United States