IU Indianapolis ScholarWorks :: Browsing by Author "Weaver, Connie M."

Browsing by Author "Weaver, Connie M."

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Associations among osteocalcin, leptin and metabolic health in children ages 9-13 years in the United States
(BioMed Central, 2017-03-07) Virecoulon Giudici, Kelly; Kindler, Joseph M.; Martin, Berdine R.; Laing, Emma M.; McCabe, George P.; McCabe, Linda D.; Hausman, Dorothy B.; Martini, Lígia Araújo; Lewis, Richard D.; Weaver, Connie M.; Peacock, Munro; Hill Gallant, Kathleen M.; Department of Medicine, IU School of Medicine
BACKGROUND: This study aimed to investigate the relationships among osteocalcin, leptin and metabolic health outcomes in children ages 9-13 years. METHODS: This was a cross-sectional analysis of baseline data from 161 boys and 157 girls (ages 9-13 years) who previously participated in a double-blinded randomized placebo controlled trial of vitamin D supplementation. Relationships among fasting serum total osteocalcin (tOC), undercarboxylated osteocalcin (ucOC), leptin, and metabolic health outcomes were analyzed. RESULTS: Approximately 52% of study participants were obese based on percent body fat cutoffs (>25% for boys and >32% for girls) and about 5% had fasting serum glucose within the prediabetic range (i.e. 100 to 125 mg/dL). Serum tOC was not correlated with leptin, glucose, insulin, HOMA-IR, or HOMA-β after adjusting for percent body fat. However, serum ucOC negatively correlated with leptin (partial r = -0.16; p = 0.04) and glucose (partial r = -0.16; p = 0.04) after adjustment for percent body fat. Leptin was a positive predictor of insulin, glucose, HOMA-IR, and HOMA-β after adjusting for age, sex and percent body fat (all p < 0.001). CONCLUSIONS: These data depict an inverse relationship between leptin and various metabolic health outcomes in children. However, the notion that tOC or ucOC link fat with energy metabolism in healthy children was not supported.
Blueberry Polyphenols do not Improve Bone Mineral Density or Mechanical Properties in Ovariectomized Rats
(Springer, 2022) Cladis, Dennis P.; Swallow, Elizabeth A.; Allen, Matthew R.; Hill Gallant, Kathleen M.; Weaver, Connie M.; Anatomy, Cell Biology and Physiology, School of Medicine
Osteoporosis-related bone fragility fractures are a major public health concern. Given the potential for adverse side effects of pharmacological treatment, many have sought alternative treatments, including dietary changes. Based on recent evidence that polyphenol-rich foods, like blueberries, increase calcium absorption and bone mineral density (BMD), we hypothesized that blueberry polyphenols would improve bone biomechanical properties. To test this, 5-month-old ovariectomized Sprague-Dawley rats (n = 10/gp) were orally gavaged for 90 days with either a purified extract of blueberry polyphenols (0-1000 mg total polyphenols/kg bw/day) or lyophilized blueberries (50 mg total polyphenols/kg bw/day). Upon completion of the dosing regimen, right femur, right tibia, and L1-L4 vertebrae were harvested and assessed for bone mineral density (BMD), with femurs being further analyzed for biomechanical properties via three-point bending. There were no differences in BMD at any of the sites analyzed. For bone mechanical properties, the only statistically significant difference was the high dose group having greater ultimate stress than the medium dose, although in the absence of differences in other measures of bone mechanical properties, we concluded that this result, while statistically significant, had little biological significance. Our results indicate that blueberry polyphenols had little impact on BMD or bone mechanical properties in an animal model of estrogen deficiency-induced bone loss.
Bone Turnover is not Influenced by Serum 25-Hydroxyvitamin D in Pubertal Healthy Black and White Children
(Elsevier B.V., 2012-10) Hill, Kathleen M.; Laing, Emma M.; Hausman, Dorothy B.; Acton, Anthony; Martin, Berdine R.; McCabe, George P.; Weaver, Connie M.; Lewis, Richard D.; Peacock, Munro; Department of Medicine, IU School of Medicine
Low serum 25-hydroxyvitamin D [25(OH)D] is common in healthy children particularly in blacks. However, serum 25(OH)D concentrations for optimal bone turnover in children is unknown and few data exist that describe effects of increasing serum 25(OH)D on bone turnover markers during puberty. The purpose of this study was to determine the relationships between serum 25(OH)D and changes in serum 25(OH)D and bone turnover in white and black pubertal adolescents. Bone turnover markers were measured in 318 healthy boys and girls from Georgia (34°N) and Indiana (40°N) who participated in a study of oral vitamin D3 supplementation (0 to 4000 IU/d). Serum 25(OH)D, osteocalcin, bone alkaline phosphatase, and urine N-telopeptide cross-links were measured at baseline and 12 weeks. Relationships among baseline 25(OH)D and bone biomarkers, and between changes over 12 weeks were determined and tested for effects of race, sex, latitude, and baseline 25(OH)D. Median 25(OH)D was 27.6 ng/mL (n=318, range 10.1–46.0 ng/mL) at baseline and 34.5 ng/mL (n=302, range 9.7–95.1 ng/mL) at 12 weeks. Neither baseline nor change in 25(OH)D over 12 weeks were associated with bone turnover. The lack of association was not affected by race, sex, latitude, or baseline serum 25(OH)D. Serum 25(OH)D in the range of 10-46 ng/mL appears to be sufficient for normal bone turnover in healthy black and white pubertal adolescents.
Effect of Hesperidin with and without a Calcium (Calcilock®) Supplement on Bone Health in Postmenopausal Women
(2016-03) Martin, Berdine R.; McCabe, George P.; McCabe, Linda; Jackson, George S.; Horcajada, Marie Noelle; Offord-Cavin, Elizabeth; Peacock, Munro; Weaver, Connie M.; Department of Medicine, IU School of Medicine
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 crossover 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, 41Ca, from bone. Results: Calcium plus hesperidin, but not hesperidin alone, improved bone calcium retention by 5.5% (P < .04). Conclusion: Calcium supplementation (Calcilock), in combination with hesperidin, is effective at preserving bone in postmenopausal women. - See more at: http://press.endocrine.org/doi/10.1210/jc.2015-3767#sthash.ztalWWcv.dpuf
Insulin Resistance and the IGF-I-Cortical Bone Relationship in Children Ages 9-13 Years
(Wiley, 2017-07) Kindler, Joseph M.; Pollock, Norman K.; Laing, Emma M.; Oshri, Assaf; Jenkins, Nathan T.; Isales, Carlos M.; Hamrick, Mark W.; Ding, Ke-Hong; Hausman, Dorothy B.; McCabe, George P.; Martin, Berdine R.; Gallant, Kathleen M. Hill; Warden, Stuart J.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.; Department of Medicine
IGF-I is a pivotal hormone in pediatric musculoskeletal development. Although recent data suggest that the role of IGF-I in total body lean mass and total body bone mass accrual may be compromised in children with insulin resistance, cortical bone geometric outcomes have not been studied in this context. Therefore, we explored the influence of insulin resistance on the relationship between IGF-I and cortical bone in children. A secondary aim was to examine the influence of insulin resistance on the lean mass-dependent relationship between IGF-I and cortical bone. Children were otherwise healthy, early adolescent black and white boys and girls (ages 9 to 13 years) and were classified as having high (n = 147) or normal (n = 168) insulin resistance based on the homeostasis model assessment of insulin resistance (HOMA-IR). Cortical bone at the tibia diaphysis (66% site) and total body fat-free soft tissue mass (FFST) were measured by peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA), respectively. IGF-I, insulin, and glucose were measured in fasting sera and HOMA-IR was calculated. Children with high HOMA-IR had greater unadjusted IGF-I (p < 0.001). HOMA-IR was a negative predictor of cortical bone mineral content, cortical bone area (Ct.Ar), and polar strength strain index (pSSI; all p ≤ 0.01) after adjusting for race, sex, age, maturation, fat mass, and FFST. IGF-I was a positive predictor of most musculoskeletal endpoints (all p < 0.05) after adjusting for race, sex, age, and maturation. However, these relationships were moderated by HOMA-IR (pInteraction < 0.05). FFST positively correlated with most cortical bone outcomes (all p < 0.05). Path analyses demonstrated a positive relationship between IGF-I and Ct.Ar via FFST in the total cohort (βIndirect Effect = 0.321, p < 0.001). However, this relationship was moderated in the children with high (βIndirect Effect = 0.200, p < 0.001) versus normal (βIndirect Effect = 0.408, p < 0.001) HOMA-IR. These data implicate insulin resistance as a potential suppressor of IGF-I-dependent cortical bone development, though prospective studies are needed.
Oral calcium carbonate affects calcium but not phosphorus balance in stage 3–4 chronic kidney disease
(Nature Publishing Group, 2013-05) Hill, Kathleen M.; Martin, Berdine R.; Wastney, Meryl; McCabe, George P.; Moe, Sharon M.; Weaver, Connie M.; Peacock, Munro; Department of Medicine, IU School of Medicine
Chronic kidney disease (CKD) patients are given calcium carbonate to bind dietary phosphorus and reduce phosphorus retention, and to prevent negative calcium balance. Data are limited on calcium and phosphorus balance in CKD to support this. The aim of this study was to determine calcium and phosphorus balance and calcium kinetics with and without calcium carbonate in CKD patients. Eight stage 3/4 CKD patients, eGFR 36 mL/min, participated in two 3-week balances in a randomized placebo-controlled cross-over study of calcium carbonate (1500 mg/d calcium). Calcium and phosphorus balance were determined on a controlled diet. Oral and intravenous 45calcium with blood sampling and urine and fecal collections were used for calcium kinetics. Fasting blood and urine were collected at baseline and end of each week of each balance period for biochemical analyses. Results showed that patients were in neutral calcium and phosphorus balance while on placebo. Calcium carbonate produced positive calcium balance, did not affect phosphorus balance, and produced only a modest reduction in urine phosphorus excretion compared with placebo. Calcium kinetics demonstrated positive net bone balance but less than overall calcium balance suggesting tissue deposition. Fasting biochemistries of calcium and phosphate homeostasis were unaffected by calcium carbonate. If they can be extrapolated to effects of chronic therapy, these data caution against the use of calcium carbonate as a phosphate binder.
Phosphorus Balance in Adolescent Girls and the Effect of Supplemental Dietary Calcium
(Wiley, 2018) Vorland, Colby J.; Martin, Berdine R.; Weaver, Connie M.; Peacock, Munro; Gallant, Kathleen M. Hill; Medicine, School of Medicine
There are limited data on phosphorus balance and the effect of dietary calcium supplements on phosphorus balance in adolescents. The purpose of this study was to determine phosphorus balance and the effect of increasing dietary calcium intake with a supplement on net phosphorus absorption and balance in healthy adolescent girls. This study utilized stored urine, fecal, and diet samples from a previously conducted study that focused on calcium balance. Eleven healthy girls ages 11 to 14 years participated in a randomized crossover study, which consisted of two 3-week periods of a controlled diet with low (817 ± 19.5 mg/d) or high (1418 ± 11.1 mg/d) calcium, separated by a 1-week washout period. Phosphorus intake was controlled at the same level during both placebo and calcium supplementation (1435 ± 23.5 and 1453 ± 28.0 mg/d, respectively, p = 0.611). Mean phosphorus balance was positive by about 200 mg/d and was unaffected by the calcium supplement (p = 0.826). Urinary phosphorus excretion was lower with the calcium supplement (535 ± 42 versus 649 ± 41 mg/d, p = 0.013), but fecal phosphorus and net phosphorus absorption were not significantly different between placebo and calcium supplement (553 ± 60 versus 678 ± 63 versus mg/d, p = 0.143; 876 ± 62 versus 774 ± 64 mg/d, p = 0.231, respectively). Dietary phosphorus underestimates using a nutrient database compared with the content measured chemically from meal composites by ∼40%. These results show that phosphorus balance is positive in girls during adolescent growth and that a calcium dietary supplement to near the current recommended level does not affect phosphorus balance when phosphorus intake is at 1400 mg/d, a typical US intake level.
Racial Differences in Cortical Bone Mass, Size and Estimated Strength at the Tibial Diaphysis in Early Pubertal Children
(Office of the Vice Chancellor for Research, 2012-04-13) Warden, Stuart J.; Ferira, Ashley J.; Laing, Emma M.; Hill, Kathleen M.; Martin, Berdine R.; Weaver, Connie M.; Peacock, Munro; Lewis, Richard D.
Osteoporotic fracture rates differ according to race, with blacks having up to half the rate of whites. The reduced fracture rate in blacks has been suggested to be due to their superior bone mass; however, mass is not the sole determinant of bone strength. Bone strength, and consequent fracture risk, is also influenced by how bone material is distributed or structured. It is likely bone structure also contributes to the lower incidence of fractures in blacks and that racial differences in bone structure have roots in childhood. The aim of this study was to assess the influence of race on pQCT-derived cortical bone mass, size and estimated strength at the tibial diaphysis in early pubertal children. 160 children were recruited, with equal subjects according to race (black, n=80; white, n=80) and sex (female, n=80; male, n=80). Subjects were at sexual maturation stages 2 or 3. Tomographic slices of the tibial diaphysis at 66% proximal from the medial malleolus were acquired using pQCT. Slices were assessed for cortical volumetric BMD (Ct.vBMD), cortical BMC (Ct.BMC), total (Tt.Ar) and cortical (Ct.Ar) area, density weighted maximum (IMAX) and minimum (IMIN) second moments of area, density-weighted polar strength-strain index (SSIP), and muscle cross-sectional area (mCSA). Group differences were assessed by two-way analysis of covariance, with race (black vs. white) and sex (female vs. male) as independent variables. Covariates included predicted years from peak height velocity (maturity offset), tibial length and mCSA. There were no interactions between race and sex (all P=0.50-0.98) or main effect for sex (all P=0.08-0.45). Blacks had 15.7% more Ct.BMC, and 10.8-11.8% larger Tt.Ar and Ct.Ar than whites (all P<0.001). The greater enhancement of Ct.BMC relative to Ct.Ar resulted in blacks having 3.6% greater Ct.vBMD than whites (P<0.001). The combination of increased cortical bone mass, size and density in blacks contributed to enhanced estimated bone strength, with IMAX, IMIN and SSIP being 20.0%, 34.5% and 25.2% greater in blacks than whites, respectively (all P<0.001). These data indicate that early pubertal black children have enhanced bone mass, size and estimated bone strength at the tibial diaphysis versus whites, independent of tibial length and mCSA. They suggest bone structural differences may contribute to observed racial differences in fracture rates and that structural divergence between races develops during childhood.
Serum 25-Hydroxyvitamin D and Intact Parathyroid Hormone Influence Muscle Outcomes in Children and Adolescents
(Wiley, 2018-11) Wright, Christian S.; Laing, Emma M.; Pollock, Norman K.; Hausman, Dorothy B.; Weaver, Connie M.; Martin, Berdine R.; McCabe, George P.; Peacock, Munro; Warden, Stuart J.; Gallant, Kathleen Hill; Lewis, Richard D.; Medicine, School of Medicine
Increases in 25-hydroxyvitamin D concentrations are shown to improve strength in adults; however, data in pediatric populations are scant and equivocal. In this ancillary study of a larger-scale, multi-sited, double-blind, randomized, placebo-controlled vitamin D intervention in US children and adolescents, we examined the associations between changes in vitamin D metabolites and changes in muscle mass, strength, and composition after 12 weeks of vitamin D3 supplementation. Healthy male and female, black and white children and adolescents between the ages of 9 and 13 years from two US states (Georgia 34°N and Indiana 40°N) were enrolled in the study and randomly assigned to receive an oral vitamin D3 dose of 0, 400, 1000, 2000, or 4000 IU/d for 12 weeks between the winter months of 2009 to 2011 (N = 324). Analyses of covariance, partial correlations, and regression analyses of baseline and 12-week changes (post-baseline) in vitamin D metabolites (serum 25(OH)D, 1,25(OH)2 D, intact parathyroid hormone [iPTH]), and outcomes of muscle mass, strength, and composition (total body fat-free soft tissue [FFST], handgrip strength, forearm and calf muscle cross-sectional area [MCSA], muscle density, and intermuscular adipose tissue [IMAT]) were assessed. Serum 25(OH)D and 1,25(OH)2 D, but not iPTH, increased over time, as did fat mass, FFST, forearm and calf MCSA, forearm IMAT, and handgrip strength (p < 0.05). Vitamin D metabolites were not associated with muscle strength at baseline nor after the 12-week intervention. Changes in serum 25(OH)D correlated with decreases in forearm IMAT, whereas changes in serum iPTH predicted increases in forearm and calf MCSA and IMAT (p < 0.05). Overall, increases in 25(OH)D did not influence muscle mass or strength in vitamin D-sufficient children and adolescents; however, the role of iPTH on muscle composition in this population is unknown and warrants further investigation.
Soluble corn fiber increases bone calcium retention in postmenopausal women in a dose-dependent manner: a randomized crossover trial
(2016) Jakeman, Steven A.; Henry, Courtney N.; Martin, Berdine R.; McCabe, George P.; McCabe, Linda D.; Jackson, George S.; Peacock, Munro; Weaver, Connie M.; Department of Medicine, IU School of Medicine
Background: Dietary soluble corn fiber (SCF) significantly improves calcium absorption in adolescents and the bone strength and architecture in rodent models. Objective: In this study, we aimed to determine the skeletal benefits of SCF in postmenopausal women. Design: We used our novel technology of determining bone calcium retention by following the urinary appearance of 41Ca, a rare long-lived radioisotope, from prelabeled bone to rapidly and sensitively evaluate the effectiveness of SCF in reducing bone loss. A randomized-order, crossover, double-blinded trial was performed in 14 healthy postmenopausal women to compare doses of 0, 10, and 20 g fiber from SCF/d for 50 d. Results: A dose-response effect was shown with 10 and 20 g fiber from SCF/d, whereby bone calcium retention was improved by 4.8% (P < 0.05) and 7% (P < 0.04), respectively. The bone turnover biomarkers N-terminal telopeptide and osteocalcin were not changed by the interventions; however, a significant increase in bone-specific alkaline phosphatase, which is a bone-formation marker, was detected between 0 and 20 g fiber from SCF/d (8%; P = 0.035). Conclusion: Daily SCF consumption significantly increased bone calcium retention in postmenopausal women, which improved the bone calcium balance by an estimated 50 mg/d. This study was registered at clinicaltrials.gov as NCT02416947.

Browsing by Author "Weaver, Connie M."

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