Teresa Binkley

Randomized Trial of Physical Activity and Calcium Supplementation on Bone Mineral Content in 3- to 5-Year-Old Children

A meta‐analysis of adult exercise studies and an infant activity trial show a possible interaction between physical activity and calcium intake on bone. This randomized trial of activity and calcium supplementation was conducted in 239 children aged 3‐5 years (178 completed). Children were randomized to participate in either gross motor or fine motor activities for 30 minutes/day, 5 days per week for 12 months. Within each group, children received either calcium (1000 mg/day) or placebo. Total body and regional bone mineral content by DXA and 20% distal tibia measurements by peripheral quantitative computed tomography (pQCT) were obtained at 0 and 12 months. Three‐day diet records and 48‐h accelerometer readings were obtained at 0, 6, and 12 months. Higher activity levels were observed in gross motor versus fine motor activity groups, and calcium intake was greater in calcium versus placebo (1354 ± 301 vs. 940 ± 258 mg/day, p < 0.001). Main effects of activity and calcium group were not significant for total body bone mineral content or leg bone mineral content by DXA. However, the difference in leg bone mineral content gain between gross motor and fine motor was more pronounced in children receiving calcium versus placebo (interaction, p = 0.05). Children in the gross motor group had greater tibia periosteal and endosteal circumferences by pQCT compared with children in the fine motor group at study completion (p < 0.05). There was a significant interaction (both p ≤ 0.02) between supplement and activity groups in both cortical thickness and cortical area: among children receiving placebo, thickness and area were smaller with gross motor activity compared with fine motor activity, but among children receiving calcium, thickness and area were larger with gross motor activity. These findings indicate that calcium intake modifies the bone response to activity in young children.

Effects of Genes, Sex, Age, and Activity on BMC, Bone Size, and Areal and Volumetric BMD

Quantitative genetic analyses of bone data for 710 inter‐related individuals 8–85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific.

Bone response to jumping is site-specific in children: a randomized trial

Skeletal loading during growth may be one way of increasing bone mass early in life. We hypothesized that children randomized to a jumping program (25 jumps/day from a 45-cm box, 5 days/week for 12 weeks) would have greater increases in hip and spine bone mineral content (BMC) and 4% distal tibia volumetric bone density than children randomized to the control group. Our secondary hypothesis was that jumping would not be as beneficial among peripubertal children as compared to prepubertal or pubertal children due to the relatively high growth rate that occurs during the peripubertal period. Fifty-four children (31 girls) ages 3-5, 7-8, 11-12, and 15-18 years were enrolled. We performed bone, anthropometric, and force plate measurements at baseline and 12 weeks. Twenty-four-hour diet recall and Tanners self-report of pubertal development were completed at baseline. Jumpers had a lower calcium intake than nonjumpers at baseline (965 +/- 403 vs 1295 +/- 465 mg/day, P < 0.01), but the groups were otherwise similar. Overall, jumpers had greater increases in total body BMC (45.0 +/- 4.9 vs 29.4 +/- 5.3 g, P = 0.03) and regional dual energy x-ray absorptiometry leg BMC (19.8 +/- 2.6 vs 11.5 +/- 2.8 g, P = 0.03) than nonjumpers at all pubertal stages. However, the 4% distal tibia bone response to jumping appeared to be modified by pubertal stage, with the greatest bone benefit from jumping observed in pubertal children (interaction of jumping group by pubertal stage, P < 0.05, for both BMC and volumetric BMD). A similar pattern was observed for spine BMC (interaction, P = 0.10). We conclude that skeletal loading increases total body and leg BMC in children, but may not have a positive effect at sites that are predominantly trabecular bone during periods of rapid growth (i.e., peripubertal period).

Methods for measurement of pediatric bone

Many experts believe that optimizing bone mineral accrual early in life may prevent childhood fractures and possibly delay the development of osteoporosis later in life. Adequate nutrition and physical activity are environmental factors important in determining whether or not children acquire an appropriate amount of bone for their body size. Pediatric diseases, or therapeutic interventions used in their treatment, may interfere with normal bone development. Although there are specific methods available for assessing pediatric bone, there is no one method that can adequately assess bone health and identify the specific bone deficits that may be occurring. Understanding the biological basis for bone deficits and the ability of various bone assessment methods to discriminate or measure these deficits is important in understanding normal bone development and how to prevent and treat pediatric bone disease. The purpose of this review is to briefly describe changes in bone with growth, to define “bone density” in biological terms, to discuss some of the issues with pediatric bone measurements, and to review the three main methods for assessing bone parameters in pediatric populations. These methods, including dual energy X-ray absorptiometry (DXA), quantitative ultrasound (QUS) and peripheral quantitative computed tomography (pQCT) will be described, the advantages and disadvantages discussed, and the relationship between bone parameters and fracture risk presented for each of the methods.

pQCT Measurement of Bone Parameters in Young Children: Validation of Technique

Dual-energy X-ray absorptiometry (DXA) measures areal bone mineral density (BMD) and is affected by bone size. Peripheral quantitative computed tomography (pQCT) measures volumetric density and should not be affected by bone size. We hypothesized that pQCT could be used to measure geometric parameters in the tibia and that bone size, not density, would correlate with weight and height in 3 and 4 yr olds. Phantom measurements indicate that accurate results for cortical volumetric bone mineral density can be obtained at cortical thickness > 2 mm with voxel/speed sizes of 0.40/20 mm/s. Correlations between pQCT measured geometric bone parameters and phantom calculations were observed (all r > 0.96). Baseline data from an ongoing trial of 101 preschool children (53 male) were used to correlate bone parameters and anthropometrics. Total cross-sectional area, cortical area, and cortical thickness correlated with weight (r = 0.54, p < 0.001; r = 0.52, p < 0. 001; r = 0.30, p = 0.002) and height (r = 0.41, p < 0.001; r = 0.55, p < 0.001; r = 0.41, p < 0.001). Because of the small cortical thickness at this age (mean = 1.2 mm) cortical density was not analyzed. In a regression model including height and weight, weight was the only predictor of total cross-sectional area (p < 0.001); cortical thickness was predicted by height (p = 0.006). Both height (p = 0.005) and weight (p = 0.05) predicted the cortical area. In summary, pQCT accurately measures total cross-sectional area, cortical area, and cortical thickness in children age 3-4 yr.

Centile curves for bone densitometry measurements in healthy males and females ages 5-22 yr.

Normative pediatric bone measurement data are necessary for defining osteopenia in children and for identifying factors associated with normal bone growth. The LMS statistical method is used to produce centile curves plotting a growth characteristic as a function of age. The purpose of this study was to provide centile curves of bone measurements using peripheral quantitative computed tomography (pQCT) and dual X-ray absorptiometry (DXA) in 231 (107 male) healthy individuals ages 5 22 yr using the LMS method. pQCT (Norland XCT 2000; Norland, Ft. Atkinson, WI) was used to image a single slice at the 20% distal tibia. Periosteal circumference, endosteal circumference, and cortical density measurements were used to obtain centile curves. Whole-body DXA (Hologic QDR 4500; Hologic, Bedford, MA) was obtained and scans were analyzed using adult whole-body software for total body bone mineral content (BMC) and total body bone area. pQCT measurements showed prepubertal expansion of the tibia that plateaued in females at age 14 and continued in males until age 18. Tibia cortical density increased during the age of puberty more gradually in females than in males. DXA measurement curves showed that total body BMC and total body bone area plateaued in females at approximately age 15, whereas male curves of the same measurements showed a continued increase.

Total Body Bone Mineral Content and Tibial Cortical Bone Measures in Preschool Children

This study was undertaken to identify factors that influence total body bone area (TBBA), total body bone mineral content (TBBMC), and tibial cortical bone measures in 239 children aged 3–5 years. We obtained information on demographic and anthropometric characteristics and measurements of diet, physical activity, and strength. In multiple regression analysis, TBBA correlated with height (p < 0.001), weight (p < 0.001), percent body fat (p < 0.001), and calcium intake (p = 0.02). TBBMC correlated with TBBA (p < 0.001), age (p = 0.001), and weight (p = 0.02) and inversely correlated with height (p < 0.001) and percent body fat (p < 0.001). Children born preterm had lower TBBMC compared with children born at term (p = 0.02). Both periosteal and endosteal circumferences were correlated with weight (both, p < 0.001) and inversely correlated with age (p = 0.006 and p = 0.003, respectively) and percent body fat (p = 0.002 and p = 0.005 respectively). Endosteal circumference was greater and cortical bone area was lower in children born preterm compared with those born at term (both, p = 0.04). Findings of higher TBBA and lower TBBMC in children with high percent body fat indicate undermineralization of bone and suggest that obesity in preschool children may have detrimental effects on total body bone mass accretion. A smaller tibial periosteal circumference and thus cross‐sectional area in children with the same weight but higher percent body fat also would lead to a biomechanical disadvantage in these children. Findings of low TBBMC and cortical bone area among children born preterm need to be confirmed in other populations. We speculate that differences in these measurements between children born preterm and at term may be caused by differences in activity.

Cross-sectional versus longitudinal associations of lean and fat mass with pQCT bone outcomes in children.

CONTEXT Cross-sectional associations for lean mass (LM) and fat mass (FM) with bone may not reflect longitudinal associations. OBJECTIVE Cross-sectional and longitudinal associations of LM and FM with radial bone measurements in children were compared. DESIGN AND PARTICIPANTS We conducted a longitudinal study on 370 (232 females) children, 8-18 yr of age. MAIN OUTCOME MEASURES LM and FM were measured by dual-energy absorptiometry. Peripheral quantitative computed tomography at the 4% radius (4R) and 20% radius (20R) measured bone mineral content (BMC), volumetric bone mineral density (vBMD), area, and strength [polar stress strain index (pSSI)]. RESULTS Males at 20R had negative FM cross-sectional and longitudinal associations with cortical area and BMC and pSSI (P < 0.02); negative cross-sectional association with total area (P < 0.001); and negative longitudinal association with cortical thickness (P < 0.001). Females at 20R had FM cross-sectional association with total area, cortical BMC, and pSSI and longitudinal associations with cortical BMC and area, vBMD, and pSSI that went from positive to negative with age and, in some cases, varied with menarche. Both sexes at 4R had a negative FM cross-sectional association with BMC and area (P < 0.001) but negative longitudinal association with vBMD (P < 0.05). LM associations with bone outcomes were generally positive, except for negative longitudinal associations with cortical BMC and vBMD in young females (P < 0.01). LM associations were greater magnitude than FM associations and often depended on age. CONCLUSIONS For males and older females, cross-sectional associations indicated a reduced bone size with higher FM, whereas longitudinal associations showed a decrease in cortical area without changes in bone size. LM was positively associated with BMC and area.

High bone mass in a female Hutterite population.

We examined a Hutterite population (n = 243) to determine if their agriculturally diverse, self‐sufficient communal lifestyle promotes optimal bone mass attainment because of adequate calcium intake and high physical activity levels during growth and young adulthood. We measured total body (TB) and lumbar bone mineral content (BMC) and bone mineral density (BMD) in 39 school‐age (younger) females and 204 working (older) females. Forty‐five percent of older females and 79% of younger females currently consumed ≥3 servings (svg) of dairy per day. Older females had lumbar (0.6 ± 1.3) and TB (1.1 ± 1.1) BMD Z scores greater than 0 (both, p < 0.001). The lumbar BMD Z score of younger females was not different from 0 (−0.1 ± 1.0; p = 0.5). Both lumbar (r = 0.46; p < 0.001) and TB (r = 0.20; p = 0.02) BMD Z scores increased with increasing age. In multiple regression analyses for older females, lumbar bone area (p < 0.001), weight (p < 0.001), current hours on feet per day (p = 0.01), colony workload (p < 0.01), and estrogen status (p = 0.06) predicted lumbar BMC. TB bone area (p < 0.001), current hours on feet per day (p < 0.01), and colony workload (p < 0.01) predicted TB BMC. For younger females, lumbar bone area (p < 0.001), weight (p < 0.01), years in present colony (p = 0.02), and menses (p < 0.001) predicted lumbar BMC. TB bone area (p < 0.001), height (p < 0.01), years in present colony (p = 0.03), and menses (p < 0.01) predicted TB BMC. The effect of colony workload could not be separated from other factors different by colony. A heritability estimate of 0.66 was calculated for lumbar BMD using mother and daughter Z scores. Adequate calcium intake during growth, high physical activity early in life, and genetic factors may be contributing to above normal BMD levels in adult female Hutterites.

High bone density in young Hutterite children

We previously reported greater than average aBMD in adult Hutterites; however, it is unknown whether higher aBMD occurs at younger ages. We examined Hutterite children to test the hypotheses that aBMD Z-scores in younger (<15 years) Hutterite children would be similar to reference data; but greater in older children after they enter the adult workforce at age 15. A secondary aim was to determine lifestyle factors associated with bone measures among Hutterite children. Hip, femoral neck, and spine BMC and aBMD were measured in 323 Hutterite children aged 8 through 19 years: 186 (108 girls) were <15 years (younger) and 137 (87 girls) were >or=15 years (older). Anthropometric measurements and activity and dietary recalls were obtained. Overall, children were lighter (Z=-0.29+/-0.72 [mean+/-SD]), shorter (Z=-0.15+/-0.86, and had lower BMIs (Z=-0.27+/-0.70) than other South Dakota children residing in the same counties (all, p<or=0.002). Older girls and boys had higher percent time in moderate+vigorous activity (21+/-10% and 29+/-11% [mean+/-SD]) than younger girls and boys (15+/-10% and 18+/-10%, both p<0.001). Younger girls and boys had high hip aBMD Z-scores (0.30+/-1.0, 0.44+/-0.97; both greater than 0 at p<or=0.002). Younger males had low spine Z-score (-0.27+/-1.15, p=0.04). None of the Z-scores for the older ages were different from 0. Controlling for covariates, miles walked/day and grip strength were associated with greater hip bone area among girls (both, p<0.05). Grip strength was associated with hip and femoral neck BMC and hip aBMD among boys (all, p<0.05). Femoral neck bone area was inversely associated with calcium intake among boys (p<or=0.05), while higher hip BMC and spine BMC and aBMD were associated with increased vitamin D intake (all, p<or=0.05). Lean mass was an independent predictor of all bone measures, while fat mass was inversely associated with most measures of bone area. In summary, contrary to our hypothesis younger Hutterite children had greater hip aBMD Z scores than the normative DXA database, whereas older children did not. We speculate that high activity levels during the rapid growth phase leads to increased bone turnover and bone size; following bone consolidation later in young adulthood this will result in greater bone size and aBMD.