Whole-body Bone Mineral Content Research Articles

Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial

Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation. The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25-100 nmol/L at 10-17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007-001716-23. Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3-62·8] vs 60·5 g [59·3-61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related. Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited. Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research.

Adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts entering puberty: a 3-year follow-up study.

To investigate changes in bone mineral density (BMD) in rhythmic gymnasts (RG) entering puberty and their age-matched untrained controls (UC) over the 36-month period, and associations with leptin, adiponectin and ghrelin over this period. Whole body (WB), lumbar spine (LS) and femoral neck (FN) BMD, WB bone mineral content (BMC), and leptin, adiponectin and ghrelin were measured in 35 RG and 33 UC girls at baseline and at 12-month intervals over the next 3 years. The change over the 36 months was calculated (∆ score). The pubertal development over the next 36 months was slower in RG compard to UC, while there was no difference in bone age development between the groups. BMD at all sites was higher in RG in comparison with UC at every measurement point. ∆LS BMD and ∆FN BMD, but not ∆WB BMD and ∆WB BMC, were higher in RG compared with UC. None of the measured hormones at baseline or their ∆ scores correlated with ∆BMD and ∆BMC in RG. Baseline fat free mass correlated with ∆WB BMD and ∆WB BMC in RG, while baseline leptin was related to ∆WB BMC, ∆WB BMD and ∆LS BMD in UC. Measured baseline hormones and their ∆ scores did not correlate with increases in bone mineral values in RG entering puberty. Although the pubertal development in RG was slower than in UC, high-intensity training appeared to increase BMD growth and counterbalance negative effects of slow pubertal develpment, lower fat mass and leptin in RG.

WHOLE BODY AND REGIONAL BONE MINERAL CONTENT AND DENSITY IN WOMEN AGED 20-75 YEARS.

Dual-energy X-ray absorptiometry (DXA) allows measurement of whole body (WB) and regional bone mineral content (BMC) and density (BMD). To measure WB and regional bone area, BMC and BMD (arms, legs, ribs and pelvis) in women of different ages. 140 women participated (age range 20-75 yrs). Three subgroups were built: 20-44 yr (30 premenopausal women), 45-59 (80 women), and 60-75 (30 women). WB DXA was performed on a Hologic QDR 4500 A bone densitometer (Hologic Inc., Bedford MA). WB BMD T-scores were calculated by using the manufacturer-provided and the NHANES 1999-2004 reference databases, while the WB BMC Z-scores - based on the latter. Statistical analysis was performed on an IBM SPSS Statistics 19.0 for Windows platform (Chicago, IL). WB BMC and BMD Z-scores were consistently lower than the reference databases showing a difference of about 0.4 - 0.5 SD. The arms, legs and ribs lost more BMC after the age of 50-55, while the pelvis - much earlier. The total decreases in BMC were highest in the pelvis (26.36 %), followed by the arms (16.81 %) and whole body (15.91 %), while the bone area decreased mostly in the pelvis (13.23 %). The age-related declines in regional BMC, bone areas and BMD follow different patterns in appendicular and axial bones.

Bone Mineral Content in Infants With Myelomeningocele, With and Without Treadmill Stepping Practice.

To study development of bone mineral content (BMC) in infants with myelomeningocele (MMC) who did or did not receive upright supported stepping practice (USSP) and in infants with typical development (TD). We tested 36 infants across the ages of 1 to 18 months. Dual-energy x-ray absorptiometry was used to collect raw BMC data for the whole body, legs, and arms, which were normalized using anthropometrics. Whole-body BMC generally increased with age; values for infants with MMC were slightly lower than those for infants with TD. Bone mineral content for legs and arms was lower for infants with MMC than for infants with TD. Between MMC groups, the group receiving USSP showed increases in BMC with age. Bone mineralization in infants with MMC begins to lag compared with infants with TD across infancy, and daily USSP can improve BMC as early as the first year of life.

Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children.

We examined fat-independent associations of hormones with height and whole-body bone size and mineral content in 633 school children. IGF-1 and osteocalcin predict growth in height, while fat, osteocalcin, and in girls also, IGF-1 predict growth in bone size. Leptin and ghrelin are inversely associated with bone size in girls. Obesity causes larger bone size and bone mass, but the role of hormones in this up-regulation of bone in obesity is not well elucidated. We examined longitudinal associations between baseline body fat mass (FM), and fat-independent fasting levels of ghrelin, adiponectin, leptin, insulin, insulin-like growth factor-I (IGF-1), osteocalcin, and intact parathyroid hormone, and subsequent changes in height and in whole-body height-adjusted bone area "BAheight" and size-adjusted bone mineral content "BMCsize" in 8- to 11-year-olds. Analyses were carried out separately for boys (n = 325) and girls (n = 308) including data from baseline, 3 and 6months from OPUS School Meal Study. In both sexes: gain in BAheight was positively associated with baseline FM (≥2.05cm(2)/kg, both p ≤ 0.003). Furthermore, gain in height was positively associated with baseline IGF-1 (≥0.02cm/ng/ml, p = 0.001) and osteocalcin (≥0.13cm/ng/ml, p ≤ 0.009); and gain in BAheight was positively associated with baseline osteocalcin (≥0.35cm(2)/ng/ml, p ≤ 0.019). In girls only, gain in BAheight was also positively associated with baseline IGF-1 (0.06cm(2)/ng/ml, p = 0.017) and inversely associated with both baseline ghrelin (-0.01cm(2)/pg/ml, p = 0.001) and leptin (-1.21cm(2)/μg/ml, p = 0.005). In boys, gain in BMCsize was positively associated with osteocalcin (0.18g/ng/ml, p = 0.030). This large longitudinal study suggests that in 8- to 11-year-old children, IGF-1 and osteocalcin predict growth in height, while FM, osteocalcin, and in girls also, IGF-1 predict growth in BAheight. Fat-independent inverse associations of leptin and ghrelin with BAheight in girls' are contrary to proposed growth-stimulating effects of leptin. Osteocalcin in boys predicts gain in BMCsize.

FIVE-YEAR OUTCOMES AFTER LONG-TERM OXANDROLONE ADMINISTRATION IN SEVERELY BURNED CHILDREN

Administration of oxandrolone, a nonaromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of oxandrolone administration. This study was undertaken to determine if administration of oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD). Patients between 0 and 18 years of age with ≥30% of total body surface area burned were consented to an IRB-approved protocol and randomized to receive either placebo (n = 84) or 0.1 mg/kg oxandrolone orally twice daily for 24 months (n = 35). Patients were followed prospectively from the time of admission until 5 years postburn in a single-center, intent-to-treat setting. Height, weight, BMC, and BMD were recorded annually through 5 years postinjury. The long-term administration of oxandrolone for 16 ± 1 months postburn (range, 12.1-25.2 months) significantly increased whole-body (WB) BMC (p < 0.02) and lumbar spine (LS) BMC (p < 0.05); these effects were significantly pronounced for a longer time in patients who were in growth spurt years (7-18 years). When adjusted for height, sex, and age, LS BMD was found to significantly increase with long-term oxandrolone administration (p < 0.0009). Fewer patients receiving oxandrolone exhibited LS BMD z scores below -2.0 as compared with controls, indicating a significantly reduced risk for future fracture with oxandrolone administration. Long-term oxandrolone patients had significantly greater height velocity than controls throughout the first 2-year postburn (p < 0.05). No adverse side effects were attributed to the long-term administration of oxandrolone. A comparison of the current patients receiving long-term oxandrolone to previously described patients receiving 12 months of oxandrolone revealed that long-term oxandrolone administration imparted significantly greater increases in WB-BMC, WB-BMD, and LS-BMD (p < 0.05). In conclusion, the administration of oxandrolone for up to 24 months to severely burned pediatric patients significantly improves WB BMC, LS BMC, LS BMD, and height velocity. The administration of long-term oxandrolone was more efficacious than administration for 12 months. Additionally, fewer patients in the oxandrolone cohort met the diagnostic criteria for pediatric osteoporosis, pointing to a reduced risk for future bone fracture. This study demonstrates that administering oxandrolone for up to 2 years following severe burn injury results in greater improvements in BMC, BMD, and height velocity.

Osteoblast-Specific Overexpression of Human WNT16 Increases Both Cortical and Trabecular Bone Mass and Structure in Mice.

Previous genome-wide association studies have identified common variants in genes associated with bone mineral density (BMD) and risk of fracture. Recently, we identified single nucleotide polymorphisms (SNPs) in Wingless-type mouse mammary tumor virus integration site (WNT)16 that were associated with peak BMD in premenopausal women. To further identify the role of Wnt16 in bone mass regulation, we created transgenic (TG) mice overexpressing human WNT16 in osteoblasts. We compared bone phenotypes, serum biochemistry, gene expression, and dynamic bone histomorphometry between TG and wild-type (WT) mice. Compared with WT mice, WNT16-TG mice exhibited significantly higher whole-body areal BMD and bone mineral content (BMC) at 6 and 12 weeks of age in both male and female. Microcomputer tomography analysis of trabecular bone at distal femur revealed 3-fold (male) and 14-fold (female) higher bone volume/tissue volume (BV/TV), and significantly higher trabecular number and trabecular thickness but lower trabecular separation in TG mice compared with WT littermates in both sexes. The cortical bone at femur midshaft also displayed significantly greater bone area/total area and cortical thickness in the TG mice in both sexes. Serum biochemistry analysis showed that male TG mice had higher serum alkaline phosphatase, osteocalcin, osteoprotegerin (OPG), OPG to receptor activator of NF-kB ligand (tumor necrosis family ligand superfamily, number 11; RANKL) ratio as compared with WT mice. Also, lower carboxy-terminal collagen cross-link (CTX) to tartrate-resistant acid phosphatase 5, isoform b (TRAPc5b) ratio was observed in TG mice compared with WT littermates in both male and female. Histomorphometry data demonstrated that both male and female TG mice had significantly higher cortical and trabecular mineralizing surface/bone surface and bone formation rate compared with sex-matched WT mice. Gene expression analysis demonstrated higher expression of Alp, OC, Opg, and Opg to Rankl ratio in bone tissue in the TG mice compared with WT littermates. Our data indicate that WNT16 is critical for positive regulation of both cortical and trabecular bone mass and structure and that this molecule might be targeted for therapeutic interventions to treat osteoporosis.

Peripheral quantitative computed tomography (pQCT) bone measurements in children with cystic fibrosis.

Individuals with cystic fibrosis (CF) have low bone density and increased fracture risk. Cross-sectional study investigating whole body bone mineral content (WBBMC), bone geometry and strength in 12 children with CF compared to 23 age- and sex-matched controls with and without adjusting for age, height, and body composition. CF group had lower WBBMC than controls (P = 0.007) with larger differences at older ages (age-by-group, P = 0.08). CF group had decreased height (P = 0.006), a trend of lower lean mass per height (P = 0.08), and no difference in relationship between WBBMC and lean mass compared to controls (P = 0.65). Periosteal and endosteal circumferences were smaller in CF (each, P = 0.02). Positive relationships of cortical area and bone strength with age were attenuated with CF (group-by-age; each, P < 0.01). Children with CF have similar WBBMC relative to lean mass as controls. Cortical bone area and bone strength were less in CF group compared to controls, with greater differences in older children.

Bone Mineral Accrual Is Associated With Parathyroid Hormone and 1,25-Dihydroxyvitamin D Levels in Children and Adolescents.

Rapid bone accrual and calcium demands during puberty may result in compensatory increases in PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels; however, these relations have not been established in longitudinal studies. To determine whether greater bone accrual velocity is associated with greater PTH and 1,25(OH)2D levels in healthy children and adolescents. Prospective cohort study with baseline PTH, 25-hydroxyvitamin D [25(OH)D], and 1,25(OH)2D levels and dual-energy x-ray absorptiometry whole-body bone mineral content (BMC) accrual over 12 months. Secondary analyses examined bone biomarkers and tibia quantitative computed tomography midshaft cortical-BMC. A total of 594 healthy participants, ages 5-21 years, with longitudinal measures in a subset of 145 participants. PTH and 1,25(OH)2D levels. PTH levels were higher during Tanner stages 3 and 4 compared to Tanner 1 (P < .05) in males and females and were inversely and significantly associated with 25(OH)D levels and dietary calcium intake. In multivariable analyses, greater bone accrual [measured directly as change in dual-energy x-ray absorptiometry-BMC (P < .001) or quantitative computed tomography-BMC (P < .05), or indirectly as growth velocity (P < .05) or greater bone-formation biomarker level (P < .01)] was associated with higher PTH levels, independent of 25(OH)D level and dietary calcium intake. Similar associations were observed between these direct and indirect indices of bone accrual and 1,25(OH)2D levels. PTH levels rise in midpuberty, in association with multiple measures of bone accrual. This is consistent with compensatory increases in PTH to drive 1,25(OH)2D production and calcium absorption during periods of increased calcium demands. Additional studies are needed to address PTH effects on bone modeling and remodeling during growth and development.

Prediction of Areal Bone Mineral Density and Bone Mineral Content in Children and Adolescents Living With HIV Based on Anthropometric Variables

Children and adolescents living with HIV have low bone mass for age. There are reliable and accurate methods for evaluation of bone mass, however, alternative methods are necessary, especially, for application in limited-resource scenarios. Anthropometry is a noninvasive and low cost method that can predict bone mass in healthy youths. The aim of the study was to develop predictive equations for bone mineral content and bone mineral density in children and adolescents living with HIV based on anthropometric variables. Forty-eight children and adolescents of both sexes (24 females) from 7 to 17 years, living in greater Florianopolis area, Santa Catarina, Brazil, who were under clinical follow-up at “Hospital Infantil Joana de Gusmão”, participated in the study. Dual-energy X-ray absorptiometry was used to evaluate whole-body bone mineral content (BMC) and areal bone mineral density (aBMD). Height, body weight, bone diameters, arm circumference, and triceps skinfold were measured and the body mass index and arm muscle area were calculated. Multiple regression models were fitted to predict BMC and aBMD, using backward selection (p ≥ 0.05). Two predictive models with high R2 values (84%–94%) were developed. Model 1 to estimate aBMD [Y = −0.1450124 + (height × 0.0033807) + (age × 0.0146381) + (body mass index × 0.0158838) + (skin color × 0.0421068)], and model 2 to estimate BMC [Y = 1095.1 + (body weight × 45.66973) + (age × 31.36516) + (arm circumference × −53.27204) + (femoral diameter × −9.594018)].The predictive models using anthropometry provided reliable estimates and can be useful to monitor aBMD and BMC in children and adolescents living with human immunodeficiency virus where limited resources are available.

Lower Newborn Bone Mineral Content Associated With Maternal Use of Tenofovir Disoproxil Fumarate During Pregnancy.

Fetal bone effects of maternal tenofovir use have not been well studied. We sought to compare whole-body bone mineral content (BMC) of newborns exposed vs not exposed to tenofovir in utero. We enrolled participants from April 2011 to June 2013 at 14 US clinical sites. Singleton infants of women with human immunodeficiency virus (HIV) infection who took tenofovir in late pregnancy (tenofovir-exposed) or no tenofovir during pregnancy (tenofovir-unexposed) were enrolled during late pregnancy or within 72 hours of birth. Infants born before 36 weeks gestation or with confirmed HIV infection were excluded. Whole-body BMC was measured in the first month of life and compared with that of the tenofovir-exposed and tenofovir-unexposed newborns, unadjusted and adjusted for covariates. Seventy-four tenofovir-exposed and 69 tenofovir-unexposed infants had evaluable BMC measurements. Tenofovir-exposed mothers were more likely to be married (31% vs 22%; P = .04) and to use boosted protease inhibitors (84% vs 62%; P = .004). Tenofovir-exposed newborns did not differ from unexposed newborns on mean gestational age (38.2 vs 38.1 weeks) or mean length (-0.41 vs -0.18) or weight (-0.71 vs -0.48) Z-scores. The mean (standard deviation) BMC of tenofovir-exposed infants was 12% lower than for unexposed infants (56.0 [11.8] vs 63.8 [16.6] g; P = .002). The adjusted mean bone mineral content was 5.3 g lower (95% confidence interval, -9.5, -1.2; P = .013) in the tenofovir-exposed infants. Maternal tenofovir use is associated with significantly lower neonatal BMC. The duration and clinical significance of this finding should be evaluated in longitudinal studies. ClinicalTrials.gov NCT01310023.

Influences of physical fitness on bone mass in women with fibromyalgia.

The aim of this study was to provide information about the relationship of bone mineral content (BMC) and density (BMD) with some physical-fitness-related variables in a sample of women with fibromyalgia (FM) and age-matched women without FM. Twenty-eight women clinically diagnosed with FM (age 51.1 ± 8.4 yr, M ± SD) and 22 age-matched controls participated in the study. Whole-body BMC and BMD, lean mass, handgrip strength, quadriceps strength, and cardiovascular fitness were measured in all participants. The association between physical-fitness variables and bone-related variables was tested by linear regression controlling for body weight as a possible confounder. There were no differences in BMC or BMD between groups. Women with FM had lower values of handgrip strength, quadriceps strength, and VO2peak than the control group. Handgrip strength and aerobic capacity were associated with BMC and BMD and quadriceps strength was associated with BMD in women with FM; however, only VO2peak was associated with BMC in the group of women without FM. Bone mass of women with FM may be more susceptible to changes in physical fitness than that of the women without fibromyalgia.

High Bone Mass-Causing Mutant LRP5 Receptors Are Resistant to Endogenous Inhibitors In Vivo.

Certain missense mutations affecting LRP5 cause high bone mass (HBM) in humans. Based on in vitro evidence, HBM LRP5 receptors are thought to exert their effects by providing resistance to binding/inhibition of secreted LRP5 inhibitors such as sclerostin (SOST) and Dickkopf homolog-1 (DKK1). We previously reported the creation of two Lrp5 HBM knock-in mouse models, in which the human p.A214V or p.G171V missense mutations were knocked into the endogenous Lrp5 locus. To determine whether HBM knock-in mice are resistant to SOST- or DKK1-induced osteopenia, we bred Lrp5 HBM mice with transgenic mice that overexpress human SOST in osteocytes ((8kb) Dmp1-SOST) or mouse DKK1 in osteoblasts and osteocytes ((2.3kb) Col1a1-Dkk1). We observed that the (8kb) Dmp1-SOST transgene significantly lowered whole-body bone mineral density (BMD), bone mineral content (BMC), femoral and vertebral trabecular bone volume fraction (BV/TV), and periosteal bone-formation rate (BFR) in wild-type mice but not in mice with Lrp5 p.G171V and p.A214V alleles. The (2.3kb) Col1a1-Dkk1 transgene significantly lowered whole-body BMD, BMC, and vertebral BV/TV in wild-type mice and affected p.A214V mice more than p.G171V mice. These in vivo data support in vitro studies regarding the mechanism of HBM-causing mutations, and imply that HBM LRP5 receptors differ in their relative sensitivity to inhibition by SOST and DKK1.

Calcium supplementation and bone mineral accretion in Chinese adolescents aged 12-14 years: a 12-month, dose-response, randomised intervention trial.

A 12-month, dose-response, randomised, intervention trial was conducted to determine adequate Ca intake levels for Chinese adolescents by investigating the effect of Ca supplementation on bone mineral accretion. A total of 220 Han adolescents (111 girls and 109 boys) aged 12-14 years were recruited. All subjects were randomly divided into three groups. The bone mineral content (BMC) and bone mineral density (BMD) of the whole body, lumbar spine (L1-L4), left hip and femoral neck were measured by dual-energy X-ray absorptiometry. Girls in the high-Ca group (actual Ca intake: 1243 (sd 193)mg/d) exhibited greater increases in the femoral neck BMC compared with those in the low-Ca group (9·7 v. 6·4%, P=0·04) over the 1-year intervention period. The increases in femoral neck BMC were greater in boys in the high-Ca and medium-Ca groups (actual Ca intake: 985 (sd 168)mg/d) than in those in the low-Ca group (15·7 v. 11·7%, P=0·03; 15·8 v. 11·7%, P=0·03). Ca supplementation had significant effects on the whole-body BMC and BMD in subjects with physical activity levels>34·86 metabolic equivalents and on the spine BMD and BMC and BMD of most sites in subjects with Tanner stage<3. Increasing Ca intake levels with Ca supplementation enhanced femoral neck mineral acquisition in Chinese adolescents. Furthermore, high physical activity levels and low Tanner stage appeared to significantly contribute to the effect of Ca supplementation on bone mass. Whether this is a lasting beneficial effect leading to the optimisation of peak bone mass needs to be determined in other long-term prospective studies.

Vitamin D Status is Associated With Bone Mineral Density and Bone Mineral Content in Preschool-Aged Children

This study examined the associations between vitamin D status, bone mineral content (BMC), areal bone mineral density (aBMD), and markers of calcium homeostasis in preschool-aged children. Children (n = 488; age range: 1.8–6.0 y) were randomly recruited from Montreal. The distal forearm was scanned using a peripheral dual-energy X-ray absorptiometry scanner (Lunar PIXI; GE Healthcare, Fairfield, CT). A subset (n = 81) had clinical dual-energy X-ray absorptiometry (cDXA) scans (Hologic 4500A Discovery Series) of lumbar spine (LS) 1–4, whole body, and ultradistal forearm. All were assessed for plasma 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone concentrations (Liaison; Diasorin), ionized calcium (ABL80 FLEX; Radiometer Medical A/S), and dietary vitamin D and calcium intakes by survey. Age (p < 0.001) and weight-for-age Z-score (p < 0.001) were positively associated with BMC and aBMD in all regression models, whereas male sex contributed positively to forearm BMC and aBMD. Having a 25(OH)D concentration of >75 nmol/L positively associated with forearm and whole body BMC and aBMD (p < 0.036). Sun index related to (p < 0.029) cDXA forearm and LS 1–4 BMC and whole-body aBMD. Nutrient intakes did not relate to BMC or aBMD. In conclusion, higher vitamin D status is linked to higher BMC and aBMD of forearm and whole body in preschool-aged children.

Internet-Delivered Lifestyle Physical Activity Intervention Improves Body Composition in Multiple Sclerosis: Preliminary Evidence From a Randomized Controlled Trial

ObjectiveTo examine the efficacy of a physical activity behavioral intervention for improving outcomes of body composition in persons with multiple sclerosis (MS). DesignSecondary analysis of data from a randomized controlled trial. SettingUniversity research laboratory. ParticipantsAmbulatory persons with MS (N=82). InterventionA 6-month, internet-delivered physical activity behavioral intervention designed to increase lifestyle physical activity, primarily walking. The behavioral intervention was based on principles of social cognitive theory. Main Outcome MeasuresWhole-body bone mineral content (BMC), bone mineral density (BMD), and soft tissue composition, using dual-energy x-ray absorptiometry. ResultsThere were no significant differences between conditions posttrial on body composition outcomes using the adjusted critical value (P<.008). There was a significant effect of the intervention on whole-body BMC (P=.04, ω2<.001) and BMD (P=.01, ω2=.003) using the unadjusted critical value (P<.05). The effect of the intervention on percent body fat (P=.09, ω2=.001) and whole-body fat mass (P=.05, ω2=.003) approached significance using unadjusted criteria. There was not a significant effect on whole-body lean soft tissue (P=.28, ω2<.001) or body mass index (P=.86, ω2<.001). ConclusionsOur results provide preliminary evidence that an internet-delivered lifestyle physical activity intervention might improve bone health and body composition in MS. Such findings are important considering that physical activity is a modifiable behavior with the potential to confer long-term benefits for the prevention and management of fracture risk and comorbidities among those with MS.

Bone Densitometry in Infants and Young Children: The 2013 ISCD Pediatric Official Positions

Infants and children <5 yr were not included in the 2007 International Society for Clinical Densitometry Official Positions regarding Skeletal Health Assessment of Children and Adolescents. To advance clinical care of very young children, the International Society for Clinical Densitometry 2013 Position Development Conference reviewed the literature addressing appropriate methods and skeletal sites for clinical dual-energy X-ray absorptiometry (DXA) measurements in infants and young children and how results should be reported. DXA whole-body bone mineral content and bone mineral density for children ≥3 yr and DXA lumbar spine measurements for infants and young children 0–5 yr were identified as feasible and reproducible. There was insufficient information regarding methodology, reproducibility, and reference data to recommended forearm and femur measurements at this time. Appropriate methods to account for growth delay when interpreting DXA results for children <5 yr are currently unknown. Reference data for children 0–5 yr at multiple skeletal sites are insufficient and are needed to enable interpretation of DXA measurements. Given the current scarcity of evidence in many areas, it is likely that these positions will change over time as new data become available.

Calcium homeostasis and bone metabolic responses to high-protein diets during energy deficit in healthy young adults: a randomized controlled trial

Although consuming dietary protein above current recommendations during energy deficit (ED) preserves lean body mass, concerns have been raised regarding the effects of high-protein diets on bone health. The objective was to determine whether calcium homeostasis and bone turnover are affected by high-protein diets during weight maintenance (WM) and ED. In a randomized, parallel-design, controlled trial of 32 men and 7 women, volunteers were assigned diets providing protein at 0.8 [Recommended Dietary Allowance (RDA)], 1.6 (2 × RDA), or 2.4 (3 × RDA) g · kg(-1) · d(-1) for 31 d. Ten days of WM preceded 21 d of ED, during which total daily ED was 40%, achieved by reduced dietary energy intake (∼30%) and increased physical activity (∼10%). The macronutrient composition (protein g · kg(-1) · d(-1) and % fat) was held constant from WM to ED. Calcium absorption (ratio of (44)Ca to (42)Ca) and circulating indexes of bone turnover were determined at day 8 (WM) and day 29 (ED). Regardless of energy state, mean (±SEM) urinary pH was lower (P < 0.05) at 2 × RDA (6.28 ± 0.05) and 3 × RDA (6.23 ± 0.06) than at the RDA (6.54 ± 0.06). However, protein had no effect on either urinary calcium excretion (P > 0.05) or the amount of calcium retained (P > 0.05). ED decreased serum insulin-like growth factor I concentrations and increased serum tartrate-resistant acid phosphatase and 25-hydroxyvitamin D concentrations (P < 0.01). Remaining markers of bone turnover and whole-body bone mineral density and content were not affected by either the protein level or ED (P > 0.05). These data demonstrate that short-term consumption of high-protein diets does not disrupt calcium homeostasis and is not detrimental to skeletal integrity. This trial was registered at www.clinicaltrials.gov as NCT01292395.

Bone Mineral Content and Density in Obese , Overweight and Normal Weight Adolescent Boys

The aim of this study was to compare bone mineral content (BMC), bone mineral density (BMD) and bone mineral apparent density (BMAD) in obese, overweight and normal weight adolescent boys. This study included 23 obese, 19 overweight and 25 normal weight adolescents (aged 14-20 years) boys. The three groups (obese, overweight and normal weight) were matched for age and maturation index. Body composition, BMC and BMD were assessed by dual-energy X-ray absorptiometry (DXA). The expressions whole body (WB) BMC/height and WB BMD/height were used to adjust for WB bone size. BMAD was calculated for the WB. WB BMC, WB BMC/height, total hip (TH) BMD, femoral neck (FN) BMD and ultra distal (UD) radius BMD) were higher in obese and overweight boys in comparison to normal weight boys (p < 0.05). WB BMAD was lower in obese boys in comparison to overweight and normal weight boys (p < 0.05). After adjustment for either weight or lean mass, obese boys displayed lower WB BMC, WB BMC/height and WB BMD values in comparison to overweight and normal weight boys (p < 0.05). This study suggests that WB BMC, WB BMC/height and WB BMD do not adapt to the increased body weight in obese adolescent boys.

Changes in DXA and Quantitative CT Measures of Musculoskeletal Outcomes Following Pediatric Renal Transplantation

This prospective study evaluated changes in dual energy X-ray absorptiometry (DXA) whole body bone mineral content (WB-BMC) and spine areal bone mineral density (spine-BMD), and tibia quantitative computed tomography (QCT) trabecular and cortical volumetric BMD and cortical area in 56 children over 12 months following renal transplantation. At transplant, spine-BMD Z-scores were greater in younger recipients (<13 years), versus 898 reference participants (p < 0.001). In multivariate models, greater decreases in spine-BMD Z-scores were associated with greater glucocorticoid dose (p < 0.001) and declines in parathyroid hormone levels (p = 0.008). Changes in DXA spine-BMD and QCT trabecular BMD were correlated (r = 0.47, p < 0.01). At 12 months, spine-BMD Z-scores remained elevated in younger recipients, but did not differ in older recipients (≥ 13) and reference participants. Baseline WB-BMC Z-scores were significantly lower than reference participants (p = 0.02). Greater glucocorticoid doses were associated with declines in WB-BMC Z-scores (p < 0.001) while greater linear growth was associated with gains in WB-BMC Z-scores (p = 0.01). Changes in WB-BMC Z-scores were associated with changes in tibia cortical area Z-scores (r = 0.52, p < 0.001), but not changes in cortical BMD Z-scores. Despite resolution of muscle deficits, WB-BMC Z-scores at 12 months remained significantly reduced. These data suggest that spine and WB DXA provides insight into trabecular and cortical outcomes following pediatric renal transplantation.