Biomedical subjects

Munro Peacock

Publications and source records attributed to Munro Peacock.

At least 19 recordsLinked to original sources

PubMed2007

Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass.

UNLABELLED: Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. INTRODUCTION: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. MATERIALS AND METHODS: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. RESULTS: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. CONCLUSIONS: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance.

Bone Density↗

PubMed2006

Human ALOX12, but not ALOX15, is associated with BMD in white men and women.

UNLABELLED: The Alox15 gene was recently identified as a negative regulator of peak BMD in mice. Polymorphisms in human ALOX12, but not ALOX15, were significantly associated with spine BMD in white men and women, suggesting that ALOX12 may contribute to normal variation in BMD. INTRODUCTION: Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporosis is peak BMD, which is a highly heritable trait. Recently, the arachidonate 15-lipoxygenase (Alox15) gene was identified as a negative regulator of peak BMD in mice. MATERIALS AND METHODS: To assess the contribution of lipoxygenase genes to normal BMD variation in healthy white men and women, we performed population- and family-based association studies of two arachidonate lipoxygenase genes: ALOX15, which is the human homolog of mouse Alox15, and ALOX12, which is functionally similar to Alox15. Single nucleotide polymorphisms (SNPs) distributed across the two genes were genotyped. BMD was measured at the femoral neck and lumbar spine in 411 men 18-61 years of age and 1291 premenopausal women 20-50 years of age. RESULTS: Moderate evidence of association was found between spine BMD and six SNPs in the ALOX12 gene in both men and women (p = 0.0052-0.050). Furthermore, the most common SNP haplotype in ALOX12 showed evidence of significant association with high spine BMD in men (p = 0.0083), whereas the second most common haplotype was associated with high spine BMD in women (p = 0.0081). CONCLUSIONS: Polymorphisms in the ALOX12 gene may contribute to normal variation in spine BMD.

Adolescent↗

PubMed2006

Sensitivity of fibroblast growth factor 23 measurements in tumor-induced osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of hypophosphatemia, decreased renal phosphate reabsorption, normal or low serum 1,25-dihydryxyvitamin-D concentration, myopathy, and osteomalacia. Fibroblast growth factor 23 (FGF23) is a phosphaturic protein overexpressed in tumors that cause TIO and is, at least partly, responsible for the manifestations of TIO. OBJECTIVE: The objective of this study was to determine the sensitivity of FGF23 measurements in TIO. DESIGN: FGF23 concentrations were measured on stored samples with three ELISAs. SETTING: This study was conducted at subspecialty referral centers. PATIENTS: Twenty-two patients with suspected TIO, 13 with confirmed tumors, were studied. INTERVENTIONS: There were no interventions in this study. MAIN OUTCOME MEASURE: FGF23 concentration was the main outcome measure of this study. RESULTS: Elevated FGF23 concentrations were detected using the Immunotopics C-terminal assay in 16 of 22 TIO patients (for a sensitivity of 73%), the Immunotopics Intact assay in five of 22 patients (sensitivity, 23%), and the Kainos Intact assay in 19 of 22 patients (sensitivity, 86%). In the 13 patients with confirmed tumors, the sensitivity was higher with all assays: 92% for the Immunotopics C-terminal assay, 38% for the Immunotopics Intact assay, and 100% for the Kainos assay. CONCLUSION: The Kainos Intact assay was the most sensitive, followed by the Immunotopics C-terminal assay. The findings of normal FGF23 concentrations in some patients with TIO may indicate that FGF 23 is not responsible for the hypophosphatemia in these patients or that FGF23 secretion by some tumors is partially responsive to serum phosphate. Normal FGF23 concentrations should be interpreted in relation to the serum phosphate and 1,25-dihydryxyvitamin-D concentrations.

Adolescent↗

PubMed2006

Denosumab in postmenopausal women with low bone mineral density.

BACKGROUND: Receptor activator of nuclear factor-kappaB ligand (RANKL) is essential for osteoclast differentiation, activation, and survival. The fully human monoclonal antibody denosumab (formerly known as AMG 162) binds RANKL with high affinity and specificity and inhibits RANKL action. METHODS: The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density (T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur). Subjects were randomly assigned to receive denosumab either every three months (at a dose of 6, 14, or 30 mg) or every six months (at a dose of 14, 60, 100, or 210 mg), open-label oral alendronate once weekly (at a dose of 70 mg), or placebo. The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months. Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase. RESULTS: Denosumab treatment for 12 months resulted in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent (as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo), at the total hip of 1.9 to 3.6 percent (as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo), and at the distal third of the radius of 0.4 to 1.3 percent (as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo). Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab. The duration of the suppression of bone turnover appeared to be dose-dependent. CONCLUSIONS: In postmenopausal women with low bone mass, denosumab increased bone mineral density and decreased bone resorption. These preliminary data suggest that denosumab might be an effective treatment for osteoporosis. (ClinicalTrials.gov number, NCT00043186.).

Alendronate↗

PubMed2006

Effect of 1-year dairy product intervention on fat mass in young women: 6-month follow-up.

OBJECTIVE: Previous results from this laboratory suggest that a 1-year dairy intake intervention in young women does not alter fat mass. The objective of this study was to determine the impact of the 1-year dairy intervention 6 months after completion of the intervention. RESEARCH METHODS AND PROCEDURES: Previously, normal-weight young women (n = 154) were randomized to one of three calcium intake groups: control (<800 mg/d), medium dairy (1000 to 1100 mg/d), or high dairy (1300 to 1400 mg/d) for a 1-year trial (n = 135 completed). In the current study, 51 women were assessed 6 months after completion of the intervention trial. Body compositions (body fat, lean mass) were measured using DXA. Self-report questionnaires were utilized to measure activity and dietary intake (kilocalories, calcium). RESULTS: The high-dairy group (n = 19) maintained an elevated calcium intake (1027 +/- 380 mg/d) at 18 months compared with the control group (n = 18, 818 +/- 292; p = 0.02). Mean calcium intake over the 18 months predicted a negative change in fat mass (p = 0.04) when baseline BMI was controlled in regression analysis (model R(2) = 0.11). 25-Hydroxyvitamin D levels were correlated with fat mass at each time-point (baseline, r = -0.41, p = 0.003; 12 months, r = -0.42, p = 0.002; 18 months, r = -0.32, p = 0.02) but did not predict changes in fat mass. DISCUSSION: Dietary calcium intake over 18 months predicted a negative change in body fat mass. Thus, increased dietary calcium intakes through dairy products may prevent fat mass accumulation in young, healthy, normal-weight women.

Absorptiometry, Photon↗

PubMed2006

Calcium retention in adolescent boys on a range of controlled calcium intakes.

BACKGROUND: National calcium requirements in the United States for boys are based on data from girls. On average, boys develop larger skeletons than do girls, yet it is unknown whether the additional skeletal accretion in boys requires additional dietary calcium intake. OBJECTIVE: The objective was to determine calcium retention in adolescent boys in response to a range of controlled intakes and to compare the intake needed for maximal retention in boys with that needed in adolescent girls studied under the same conditions. DESIGN: Thirty-one boys aged 12-15 y participated in 3-wk metabolic balance studies testing a range (700-2100 mg/d) of calcium intakes in a crossover study design with a 2-wk washout period. Calcium intake was varied by using a beverage fortified with calcium citrate malate. After a 1-wk equilibration period, calcium retention was calculated as dietary calcium intake minus the calcium excreted in the feces and urine over the following 2 wk. The dietary intake at which maximal calcium retention occurred was determined by using a nonlinear regression model. The results in boys were compared with those obtained in 35 adolescent girls previously studied under the same protocol. RESULTS: Maximal calcium retention in boys was achieved at an intake of 1140 mg/d. Calcium retention was higher (by 171 +/- 38 mg/d) in boys than in girls at all calcium intakes studied. CONCLUSION: The higher calcium retention in boys than in girls was attained through higher net calcium absorption and lower urinary excretion than in girls.

Adolescent↗

PubMed2006

Heritability of changes in bone size and bone mass with age in premenopausal white sisters.

UNLABELLED: Femoral neck area expands and BMD decreases in premenopausal women. We used longitudinal DXA measurements on 388 premenopausal white sisters to show significant heritability of the rates of change in femoral neck area, BMC, and BMD. INTRODUCTION: Bone mass and structure are highly heritable. However, genetic effects on age-related changes in bone mass and structure in adults have been much less studied. MATERIALS AND METHODS: DXA measurements were made on 388 healthy white premenopausal sisters from 178 families. Rates of change in femoral neck area, BMC, and BMD, as well as body weight, were calculated from two measurements made an average of 5.7 years apart. Mixed models were used to test whether bone changes were related to age or weight change. Variance components models were used to estimate the heritability of the rates of change. A method was proposed to correct for the underestimation of heritabilities caused by measurement errors of the rates of change. RESULTS: Femoral neck area increased with age, whereas BMD decreased. All of the rates of change at the femoral neck were positively correlated with weight change, but the rates of femoral neck changes did not vary with age. Adjusted for weight change, change in femoral neck BMC became negative. Significant heritabilities (0.29-0.36) were detected for changes in femoral neck BMC, BMD, and area adjusted for weight changes. Correction for DXA measurement error in the rate estimates increased the heritability estimates (from 0.29-0.36 range to 0.37-0.64 range). CONCLUSIONS: Rates of change are heritable for femoral neck area, BMC, and BMD in premenopausal white women.

Adult↗

PubMed2005

Two-year clinical trial of oral alendronate versus intravenous pamidronate in children with osteogenesis imperfecta.

UNLABELLED: A 2-year prospective, partially randomized open-label trial comparing oral alendronate with intravenous pamidronate therapy in children with OI showed equivalence in increasing total body BMD, spine BMD, and linear growth, and decreasing bone turnover and fracture incidence. Children with mild OI had greater responses than severe OI in BMD and growth. INTRODUCTION: Bisphosphonate therapies increase BMD and may reduce fractures in children with osteogenesis imperfecta (OI). A study directly comparing oral with intravenous bisphosphonate has not been published. This clinical trial compares oral alendronate with intravenous pamidronate in children with OI using an open-label, prospective, 2-year, randomized design. MATERIALS AND METHODS: Children over the age of 3 years were stratified by bone age, pubertal stage, and type of OI and then randomized to receive oral alendronate 1 mg/kg/day in tablet form or intravenous pamidronate, 3 mg/kg/4 months. One child was assigned to pamidronate. One child randomized to intravenous pamidronate changed to oral alendronate. Eighteen children completed 12 months of therapy: nine on oral alendronate and nine on intravenous pamidronate. Primary outcome efficacy was increase in BMD. Secondary outcomes included changes in bone turnover biomarkers, fracture incidence, and growth. RESULTS: Total body and lumbar spine BMD increased, turnover markers decreased, and linear growth increased equivalently with oral and intravenous therapy. Fracture incidence showed a trend to decrease in both groups, with a significant decrease in fracture rates when the oral and intravenous groups were pooled. There were greater responses in BMD and growth in children with milder OI (type I) than those with more severe disease (types III and IV), but there were no significant effects of age or pubertal stage. CONCLUSIONS: Oral and intravenous bisphosphonate therapies are equally effective in children with OI and are particularly effective in milder forms. The oral route is highly acceptable in children and has practical advantages over the intravenous route.

Administration, Oral↗

PubMed2005

Polymorphisms in the estrogen receptor beta (ESR2) gene are associated with bone mineral density in Caucasian men and women.

CONTEXT: A major determinant of osteoporotic fractures is peak bone mineral density (BMD), which is a highly heritable trait. Recently, we identified significant linkage for hip BMD in premenopausal sister pairs at chromosome 14q (LOD score = 3.5), where the estrogen receptor beta gene (ESR2) is located. OBJECTIVE: The objective of the study was to determine whether ESR2 polymorphisms are associated with normal BMD variation. DESIGN: This was a population-based genetic association study, using 11 single nucleotide polymorphisms (SNPs) distributed across the ESR2 gene. SETTING: The study was conducted at an academic research laboratory and medical center. PATIENTS AND OTHER PARTICIPANTS: A total of 411 healthy men (aged 18-61 yr) and 1291 healthy premenopausal women (aged 20-50 yr) living in Indiana participated in the study. INTERVENTION(S): There were no interventions. MAIN OUTCOME MEASURE(S): The main outcome measures were SNP genotype distributions and their association with BMD at the femoral neck and lumbar spine. RESULTS: Significant association of spine BMD was found with three SNPs in men and one SNP in women (P < or = 0.05). The conditional linkage analysis using the ESR2 haplotypes showed that the ESR2 gene accounts for, at most, 18% of the original linkage. CONCLUSIONS: ESR2 polymorphisms are significantly associated with bone mass in both men and women. However, the ESR2 gene is not entirely responsible for our original linkage, and an additional gene(s) in chromosome 14q contributes to the determination of BMD.

Adult↗

PubMed2005

Dietary calcium intake protects women consuming oral contraceptives from spine and hip bone loss.

CONTEXT: It is estimated that 80% of all women have used oral contraceptives (OCP), but OCP use may prevent attainment of maximal peak bone mass in young women and thus increase the risk of osteoporosis later in life. OBJECTIVE: This study examined whether increased calcium intake could reduce the detrimental effects of OCP use on bone mass in young women. DESIGN: The study design was a 1-yr intervention. SETTING: The study was performed in a general community setting. SUBJECTS: One hundred fifty-four young (18-30 yr old) healthy women with a dietary calcium intake of less than 800 mg/d began the study, and 135 completed the trial. INTERVENTION: Subjects were randomly assigned to one of three diet intervention groups: 1) control, continuous established (<800 mg/d) dietary calcium intake; 2) medium dairy, increase calcium intake to approximately 1000-1100 mg/d; and 3) high dairy, increase calcium intake to approximately 1200-1300 mg/d. Randomization was stratified by OCP use. MAIN OUTCOME MEASURES: The main outcome measures were total body bone mineral density (BMD) and content (BMC); total hip BMD, BMC, and bone area; and spine BMD, BMC, and bone area. RESULTS: Dairy product intervention positively impacted the percentage change in total hip BMD and BMC. In addition, dairy product intake prevented a negative percentage change in total hip and spine BMD in OCP users. CONCLUSION: Dairy product intake, at levels necessary to achieve the recommended intakes of calcium, protected the total hip BMD and spine BMD from loss observed in young healthy women with low calcium intakes who were using OCP.

Absorptiometry, Photon↗

PubMed2005

Sex-specific and non-sex-specific quantitative trait loci contribute to normal variation in bone mineral density in men.

INTRODUCTION: A major determinant of osteoporotic fracture is peak bone mineral density (BMD). In women peak BMD is highly heritable and several quantitative trait loci (QTL) have been reported. There are few comparable data in men. This study in men aimed to establish the heritability of peak BMD, identify QTL contributing to normal variation in BMD, and determine which QTL might be sex specific. METHODS: BMD at the spine and hip were measured in 323 pairs of brothers aged 18-61 yr (264 white pairs; 59 black pairs). Heritability was calculated and linkage analysis performed with spine and hip BMD phenotypes. RESULTS: Heritability estimates ranged from 0.61 to 0.87 and were not significantly different between white and black men. A 9-cM genome-wide scan followed by genotyping with more closely spaced markers identified suggestive QTL (logarithm of the odds > 2.2) for BMD on chromosomes 1q (spine), 2p (spine), 2q (hip), 14p (spine), 18 (hip), and 21 (hip). Comparison with published data in 774 pairs of premenopausal sisters suggested that the QTL on 1q (spine), 2q (hip), 14p (spine), and 21q (hip) were male specific, whereas those on 2p (spine) and 18 (hip) were not sex specific. CONCLUSIONS: This study demonstrates that BMD in healthy men is highly heritable with similar estimates of the genetic contribution to BMD in both whites and blacks. Of the six QTL identified, three were specific for spine BMD and three were specific for hip BMD. When compared with published QTL for peak BMD in women from the same geographical region, four of the QTL appeared to be male specific. The occurrence of sex-specific genes in humans for BMD has potentially important implications for the pathogenesis and treatment of osteoporosis.

Adolescent↗

PubMed2005

Sex-specific quantitative trait loci contribute to normal variation in bone structure at the proximal femur in men.

Bone structure is an important determinant of osteoporotic fracture. In women, bone structure is highly heritable, and several quantitative trait loci (QTL) have been reported. There are few comparable data in men. This study in men aimed at establishing the heritability of bone structure at the proximal femur, identifying QTL contributing to normal variation in bone structure, and determining which QTL might be sex-specific. Bone structure at the proximal femur was measured in 205 pairs of brothers age 18-61. Heritability was calculated, and linkage analysis performed on phenotypes at the proximal femur. Heritability estimates ranged from 0.99 to 0.39. A genome wide scan identified suggestive QTL (LOD>2.2) for femoral shaft width on chromosome 14q (LOD=2.69 at position 99 cM), calcar femorale at chromosome 2p (LOD=3.97 at position 194 cM) and at the X chromosome (LOD=3.01 at position 77 cM), femoral neck width on chromosome 5p (LOD=2.28 at position 0 cM), femoral head width on chromosome 11q (LOD=2.30 at position 131 cM) and 15q (LOD=3.11 at position 90 cM), and pelvic axis length on chromosome 4q (LOD=4.16 at position 99 cM) and 17q (LOD=2.80 at position 112 cM). Comparison with published data in 437 pairs of premenopausal sisters from the same geographical region suggested that 3 of the 7 autosomal QTL were male-specific. This study demonstrates that bone structure at the proximal femur in healthy men is highly heritable. The occurrence of sex-specific genes in humans for bone structure has important implications for the pathogenesis and treatment of osteoporosis.

Adult↗

PubMed2005

Dairy products do not lead to alterations in body weight or fat mass in young women in a 1-y intervention.

BACKGROUND: Previous results suggested that increased intake of dairy calcium is associated with reduced weight and fat mass. OBJECTIVE: The purpose of this study was to determine whether long-term increases in consumption of dairy calcium alter body weight and fat mass in young, healthy women. DESIGN: We used a randomized, 1-y intervention for dairy calcium. Subjects were 155 young (aged 18-30 y), healthy, normal-weight women with intake of dietary calcium < 800 mg/d and energy intake </= 2200 kcal/d. Women were randomly assigned to 1 of 3 groups: 1) control: continue established dietary intake; 2) medium dairy: substitute dairy products to achieve intake of calcium of approximately 1000-1100 mg/d and maintain isocaloric intake; 3) high dairy: substitute dairy products to achieve intake of calcium of 1300-1400 mg/d and maintain isocaloric intake. The main outcome measures were 1-y changes in body weight (in kg) and fat mass (in kg). One hundred thirty-five women completed the trial. RESULTS: Mean intakes of calcium during the intervention were 742.4 +/- 321.5, 1026.4 +/- 311.3, and 1131.29 +/- 337.2 mg/d for the control, medium-dairy, and high-dairy groups, respectively (P < 0.0001). No significant differences were observed in the mean 1-y change in body weight between the control, medium-dairy, and high-dairy groups (0.8 +/- 2.8, 0.7 +/- 3.0, and 1.5 +/- 4.1 kg, respectively; P = 0.45). No significant differences were observed in the mean 1-y change in fat mass between the control, medium-dairy, and high-dairy groups (-0.5 +/- 2.5, 0.3 +/- 2.7, and 0.5 +/- 3.5 kg, respectively; P = 0.26). CONCLUSION: Increased intake of dairy products does not alter body weight or fat mass in young, healthy women over 1 y.

Adipose Tissue↗

PubMed2005

Racial differences in calcium retention in response to dietary salt in adolescent girls.

BACKGROUND: Sodium is an important determinant of urinary calcium excretion, and race is an important determinant of calcium retention. The effect of dietary sodium on calcium retention and the influence of race have not been studied in adolescence, the life stage during which peak bone mass is accrued. OBJECTIVE: The study reported here was undertaken to compare racial differences in calcium retention as a function of dietary salt intake. DESIGN: A total of 35 adolescent girls (22 black and 13 white) participated in two 20-d metabolic summer camps, separated by 2 wk, that simulated a free-living environment. The effect of changes in dietary sodium on calcium retention was tested in a randomized-order, crossover design with 2 concentrations of sodium-1.30 g/d (57 mmol/d) and 3.86 g/d (168 mmol/d)-and a constant calcium intake of 815 mg/d (20 mmol/d). RESULTS: Both race and sodium intake significantly affected calcium retention (P < 0.01). Calcium retention was significantly greater in black girls than in white girls, regardless of dietary sodium intake (P < 0.001). The high-sodium diet significantly reduced calcium retention in both whites and blacks (P < 0.01), primarily through a decrease in net calcium absorption. Black girls excreted significantly less calcium in the urine than did white girls, regardless of diet (P < 0.05). CONCLUSIONS: Calcium retention is significantly greater in black girls than in white girls but is significantly reduced in girls of both races in response to salt loading.

Adolescent↗

PubMed2005

The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women: a randomized crossover study.

BACKGROUND: Evidence suggests that soy isoflavones act as estrogen agonists and have beneficial skeletal effects, but the effects on calcium metabolism in humans are not known. OBJECTIVE: This study tested whether soybean isoflavones, soy protein, or both alter calcium metabolism in postmenopausal women. DESIGN: Calcium metabolism in 15 postmenopausal women was studied by using metabolic balance and kinetic modeling in a randomized, crossover design of three 1-mo controlled dietary interventions: soy protein isolate enriched with isoflavones (soy-plus diet), soy protein isolate devoid of isoflavones (soy-minus diet), and a casein-whey protein isolate (control diet). RESULTS: There was no significant difference between the diets in net acid excretion (P = 0.12). Urinary calcium excretion was significantly (P < 0.01) less with consumption of either of the soy diets (soy-plus diet: 85 +/- 34 mg/d; soy-minus diet: 80 +/- 34 mg/d) than with consumption of the control diet (121 +/- 63 mg/d), but fractional calcium absorption was unaffected by treatment. Endogenous fecal calcium was significantly (P < 0.01) greater with consumption of the soy-minus diet than with consumption of the other diets. Total fecal calcium excretion, bone deposition and resorption, and calcium retention were not significantly affected by the dietary regimens. CONCLUSIONS: The lower urinary calcium seen with the consumption of an isolated soy protein than with that of an isolated milk protein was not associated with improved calcium retention. This finding reinforces the importance of evaluating all aspects of calcium metabolism. Soy isoflavones did not significantly affect calcium metabolism.

Body Mass Index↗

PubMed2005

Fat oxidation and its relation to serum parathyroid hormone in young women enrolled in a 1-y dairy calcium intervention.

BACKGROUND: Increased dietary calcium is associated with changes in body composition. One proposed mechanism is that dietary calcium increases fat oxidation, potentially via regulation of serum parathyroid hormone (PTH) concentrations. OBJECTIVES: The objectives of the study were to determine whether acute or chronic increased dairy calcium intakes alter postprandial whole-body fat oxidation and whether the increased intake is related to changes in PTH concentrations. DESIGN: Normal-weight women aged 18-30 y were randomly assigned to a low (<800 mg/d, control; n = 10) or high (1000-1400 mg/d; n = 9) dietary calcium intake group for 1 y. Whole-body fat oxidation was assessed by measuring respiratory gas exchange after each subject consumed 2 isocaloric liquid meals containing 100 or 500 mg Ca at baseline and 1 y. Fasting serum PTH was measured at baseline and 1 y. RESULTS: The mean 1-y change in fat oxidation was higher in the high-calcium group than in the low-calcium control group after a low-calcium meal (0.10 +/- 0.05 compared with 0.005 +/- 0.04 g/min; P < 0.001) and a high-calcium meal (0.06 +/- 0.05 compared with 0.03 +/- 0.04 g/min; P < 0.05). The 1-y change in serum log PTH was negatively associated with the 1-y change in postprandial fat oxidation after a high-calcium meal (partial r = -0.46, P < 0.04) when controlled for the1-y change in total body fat mass. CONCLUSIONS: The results suggest that a chronic diet high in dairy calcium increases whole-body fat oxidation from a meal, and increases in fasting serum PTH relate to decreases in postprandial whole-body fat oxidation.

Adipose Tissue↗

PubMed2004

Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism.

Calcimimetics increase the sensitivity of parathyroid calcium-sensing receptors to extracellular calcium, thereby reducing PTH secretion. This multicenter, randomized, double-blind, placebo-controlled study assessed the ability of the oral calcimimetic cinacalcet HCl to achieve long-term reductions in serum calcium and PTH concentrations in patients with primary hyperparathyroidism (HPT). Patients (n = 78) were randomized to cinacalcet or placebo. Cinacalcet was titrated from 30-50 mg twice daily during a 12-wk dose-titration phase. Efficacy was assessed during 12-wk maintenance and 28-wk follow-up phases. The primary endpoint was the achievement of normocalcemia [serum calcium </= 10.3 mg/dl (2.57 mmol/liter)] with at least 0.5 mg/dl (0.12-mmol/liter) reduction from baseline. Plasma PTH, serum and urine biochemistry, biochemical measures of bone turnover, bone mineral density, and safety were also assessed. Seventy-three percent of cinacalcet-treated patients vs. only 5% of placebo-treated patients achieved the primary endpoint (P < 0.001). Fasting predose plasma PTH decreased 7.6% in cinacalcet patients but increased 7.7% in placebo patients (P < 0.01). Bone mineral density was unchanged by cinacalcet, but bone resorption and formation markers increased (P < 0.05). Adverse events were mild and similar between treatment groups. Cinacalcet rapidly normalizes serum calcium and reduces PTH in patients with primary HPT, and these effects are maintained with long-term treatment. Cinacalcet may be an effective, nonsurgical approach for management of primary HPT.

Adult↗

PubMed2004

Contribution of the LRP5 gene to normal variation in peak BMD in women.

UNLABELLED: The role of the LRP5 gene in rare BMD-related traits has recently been shown. We tested whether variation in this gene might play a role in normal variation in peak BMD. Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample. INTRODUCTION: Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene have been implicated as the cause of multiple distinct BMD-related rare Mendelian phenotypes. We sought to examine whether the LRP5 gene contributes to the observed variation in peak BMD in the normal population. MATERIALS AND METHODS: We genotyped 12 single nucleotide polymorphisms (SNPs) in LRP5 using allele-specific PCR and mass spectrometry methods. Linkage disequilibrium between the genotyped LRP5 SNPs was measured. We tested for association between these SNPs and both hip and spine BMD (adjusted for age and body weight) in 1301 healthy premenopausal women who took part in a sibling pair study aimed at identifying the genes underlying peak bone mass. Our study used both population-based (ANOVA) and family-based (quantitative transmission disequilibrium test) association methodology. RESULTS AND CONCLUSIONS: The linkage disequilibrium pattern and haplotype block structure within the LRP5 gene were consistent with that observed in other studies. Although significant evidence of association was found between LRP5 SNPs and both hip and spine BMD, only a small proportion of the total variation in these phenotypes was accounted for. The genotyped SNPs accounted for approximately 0.8% of the variation in femoral neck BMD and 1.1% of the variation in spine BMD. Results from our sample suggest that natural variation in and around LRP5 is not a major contributor to the observed variability in peak BMD at either the femoral neck or lumbar spine in white women.

Adult↗