Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health, vol. -, no. -, 1e8, 2014 Ó Copyright 2014 by The International Society for Clinical Densitometry 1094-6950/-:1e8/$36.00 http://dx.doi.org/10.1016/j.jocd.2014.04.121

Original Article

Vitamin D Status is Associated With Bone Mineral Density and Bone Mineral Content in Preschool-Aged Children Tom J. Hazell,1,2 Thu Trang Pham,2 Sonia Jean-Philippe,2 Sarah L. Finch,2 Jessy El Hayek,2,3 Catherine A. Vanstone,2 Sherry Agellon,2 Celia J. Rodd,4,5 and Hope A. Weiler*,2 1

Department of Kinesiology and Physical Education, University of Lethbridge, Lethrbidge, AB, Canada; 2Mary Emily Clinical Nutrition Research Unit, School of Dietetics and Human Nutrition, McGill University, Ste-Anne-de-Bellevue, QC, Canada; 3Faculty of Nursing and Health Sciences, Notre Dame University, Zouk Mikael, Lebanon; 4Department of Pediatrics, McGill University, Montreal, QC, Canada; and 5The Montreal Children’s Hospital, Montreal, QC, Canada

Abstract 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 5 488; age range: 1.8e6.0 y) were randomly recruited from Montreal. The distal forearm was scanned using a peripheral dualenergy X-ray absorptiometry scanner (Lunar PIXI; GE Healthcare, Fairfield, CT). A subset (n 5 81) had clinical dual-energy X-ray absorptiometry (cDXA) scans (Hologic 4500A Discovery Series) of lumbar spine (LS) 1e4, 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 O75 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 1e4 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. Key Words: Bone mineral content; bone mineral density; calcidiol; young children. more than 1 yr of age assuming minimal sun exposure (2). The Canadian Paediatric Society (CPS) suggests a target of 25(OH)D concentration of above 75 nmol/L (30 ng/mL) (3) on the basis of an observed plateau in parathyroid hormone (PTH) concentration in adolescents and adults (4). Vitamin D status of children in North America is reliant on exogenous sources and tissue stores for almost half of the year because ultraviolet beta (UVB) solar radiation above w35 latitude is too low to elicit endogenous synthesis from November to March (5). Canadian children (3e5 y) have an average 25(OH)D concentration of 74 nmol/L with 89% above the 50 nmol/L cut-off (6), whereas 61%e70% of US children (1e13 yr) are above 50 nmol/L (7). However, no group has been able to establish if higher vitamin D status in accordance with suggested cut-offs is related to bone

Introduction Serum 25-hydroxyvitamin D [25(OH)D] reflects vitamin D derived from foods, supplements, and endogenous synthesis (1). The target for healthy vitamin D status is debatable, with the Institute of Medicine (IOM) suggesting a target of 25(OH)D concentration of above 50 nmol/L (20 ng/mL) in support of bone health (2). This target aligns with the Recommended Dietary Allowance (RDA) of 15 mg/d for children Received 03/04/14; Accepted 04/17/14. *Address correspondence to: Hope A. Weiler, PhD, RD, Mary Emily Clinical Nutrition Research Unit, School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Ste-Anne-de-Bellevue, QC, Canada H9X 3V9. E-mail: [email protected]

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2 outcomes in preschool-aged children. One study conducted in the Canadian Arctic showed a low median plasma 25(OH)D concentration (46.7 nmol/L), but standard assessments of bone mass were not feasible (8). The implications of low vitamin D status are less than optimal bone growth because of impairment in calcium absorption and growth plate development (9). PTH and ionized calcium (iCa) are important outcomes of vitamin D status affecting endochondral expansion of bone and areal bone mineral density (aBMD) (9). Calcium homeostasis and adequate vitamin D status are necessary to attain peak bone mineral accretion during growth (10). Indeed, vitamin D, calcium, and milk intakes are positively associated with aBMD and bone mineral content (BMC) in older children (8e11 yr) and adolescents (12e20 yr) (11e14); however, data on younger children are not available. Therefore, this study examines the association between vitamin D status, aBMD, BMC, PTH, iCa, and dietary intakes in preschool-aged children.

Materials and Methods Participants A total of 488 children (age range: 1.8e6 yr) were studied between June 2010 and June 2011 from a random sample of licensed day cares (n 5 77) in the Montreal area (73 W, 45 N). This study was a secondary question from a larger study where detailed methods have been published (15), and children were recruited proportionally by season. A registered dietitian observed each child’s dietary intake while attending day care, and dietary intake at home was collected by a subsequent telephone-based parental recall. A registered nurse collected each child’s anthropometric measurements, skin pigmentation, forearm aBMD, and a capillary blood sample. Inclusion criteria included healthy term-born children. Exclusion criteria included diseases known or associated with disturbances in bone metabolism as previously described (15).

Ethics The McGill University Faculty of Medicine Institutional Review Board approved this study. Parents or legal guardians provided written informed consent before inclusion of their child in the study.

Dietary Data Twenty-four hour assessments were collected using established methodology (16,17) and a validated 30-d food frequency questionnaire was collected to obtain usual intakes of calcium and vitamin D (15). Nutrient intake was analyzed using Nutritionist ProÔ (Axxya Systems LLC, Stafford, TX) and the Canadian Nutrient File version 2010b (Health Canada, Ottawa, ON). Data were transformed into food group servings according to Canada’s Food Guide (18).

Anthropometry Height and body weight were measured using standard procedures (15) and body mass index (BMI, kilograms per square meter) calculated. Weight-for-age (WAZ), height-for-

Hazell et al. age (HAZ), and BMI-for-age (BAZ) Z-scores were calculated using the World Health Organization software (AnthroPlus, Geneva, Switzerland).

Skin Pigmentation Skin type was established by taking the average of three measurements at each site for composite facultative (forehead, forearm, and lower leg combined) and constitutive (inner upper arm) skin tone using a spectrophotometer (CM-700 d/600d; Konica Minolta, Ramsey, NJ). Individual typological angle (degree) was calculated using the equation  from the Commission Internationale de l’Eclairage (19) and classified into Fitzpatrick skin types (20,21).

Bone Measurements From the total sample of 516 children, 488 peripheral dualenergy X-ray absorptiometry (pDXA; PIXI; GE Medical Systems Lunar, Madison, WI) scans provided aBMD of the nondominant distal one-third of radius and ulna and is valid for use in this age group (22), with an effective dose of less than 0.1 mSV. The pDXA forearm phantom with a known density (0.433 g/cm2) yielded a coefficient of variation (CV) of 0.5% (942 scans) over the study duration. A subset (n 5 78) of children underwent fan-beam clinical DXA (cDXA) scans (APEX version 13.2:3; Hologic 4500A Discovery Series, Bedford, MA) while wearing standardized clothing (shorts and T-shirt) to capture BMC and aBMD of whole body, lumbar spine 1e4 (LS 1e4) and distal onethird forearm (nondominant), the later is in closest agreement with the PIXI scan (22). The cDXA spine phantom with known density (1.024 g/cm2) yielded a BMD CV of 0.3% (244 scans). Effective X-ray dose for all scans combined was 8.6 mSV (23). Of the 78 children, all were successfully scanned with no movement breaks in the images for LS 1e4, 71 for whole body and 59 for forearm.

Other Questionnaires Caregivers provided information regarding socioeconomic status (education and household income) via telephone. Data regarding sun exposure during the previous month were collected as a percentage of body surface area (BSA) exposed, frequency of sunscreen use, and total hours spent in direct sunlight per day was surveyed at day care and at home (15). Sun index was calculated for each child by multiplying the percentage of BSA exposed by the time spent outside (minutes per day) based on the Lund and Browder chart (24).

Laboratory Analysis A nonfasted 1.1 mL capillary blood sample (heparinized) was collected between 0800 and 1200 h (15). Plasma total 25(OH)D and bioactive 1-84 PTH concentrations were measured using a chemiluminescence assay (Liaison; Diasorin, Stillwater, MN). The inter- and intra-assay CV for high and low assay controls were !8% for 25(OH)D and 15% for PTH. iCa was measured in 0.1 mL whole blood (ABL80 FLEX; Radiometer Medical A/S, Copenhagen, Denmark)

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with the manufacturer’s normal range from 1.15 to 1.38 mmol/L. National Institute for Standards and Technology controls were within 3.28% of expected values.

Statistical Analysis Seasons were defined using equinox and solstice dates (5). Skin type based on facultative skin pigmentation was collapsed into three groups: (1) fair (I and II), (2) neutral (III and IV), or (3) dark (V and VI) skin. PTH was classified as either low (!1.06 pmol/L) or normal (1.06e5.83 pmol/ L). Vitamin D status classifications included two different 25(OH)D cut-offs: IOM (50 nmol/L) (2) and CPS (75 nmol/L) (3). Nutrition data were explored as daily nutrient intake or food group servings (calcium, vitamin D, milk and alternatives, and use of a vitamin D supplement) and if the child met the estimated average requirement and RDA for vitamin D intake. Exploratory analyses by analysis of variance and bivariate correlations (with quantitative predictors) were used to examine the data. Model construction began with a model containing age, HAZ, WAZ, and sex. Single variables were then

added to the model and those that were significant or that improved the model (R2 O 2%) were included. Models were then checked for interactions and any interaction terms were included in the final regression models. Normality of each outcome was tested by visual examination. Multicollinearity and model assumptions were tested by standard post hoc methods. Nonnormal data were log transformed where applicable [PTH and 25(OH)D]. Data are presented as mean  standard deviation (SD), probability of !0.05, and analyses performed using SAS (v9.2; SAS, Cary, NC).

Results The study population consisted of 488 healthy preschoolaged children from Montreal area day cares (Table 1). None of the children were more than 2 SD below the mean, and only 5 (1%) were more than þ2 SD above the mean for BAZ. The median annual household income was greater than $75,000 Canadian dollars. There was no difference in any socioeconomic, biochemical, or nutritional variables between those with the partial or full DXA assessment. The

Table 1 Child Characteristics Variable Age (y) Sex (male), n (%) Weight (kg) WAZ Height (cm) HAZ Body mass index (kg/m2) BAZ PIXI forearm aBMD (g/cm2) Ethnicity (white), n (%)a Facultative skin classification (fair skin), n (%)b Sun index (min/d) Plasma 25(OH)D (nmol/L) Ionized calcium (mmol/L) Vitamin D intakec (IU/d) (IU/kg/d) Calcium intakec (mg/d) (mg/kg/d) Milk intakec (servings/d) FFQ vitamin D intake (IU/d) FFQ calcium (mg/d) FFQ milk intake (servings/d)

All children (n 5 516)

Partial assessment (n 5 438)

Full assessment (n 5 78)

p value

3.7  1.0 272 (52.7) 16.4  3.1 0.3  0.9 100.6  8.5 0.0  1.0 16.1  1.5 0.5  1.0 0.234  0.033 272 (50.4) 354 (68.6)

3.7  1.0 233 (53.2) 16.4  3.0 0.3  0.9 100.4  8.4 0.0  1.0 16.1  1.5 0.5  1.0 0.234  0.033 209 (47.7) 290 (66.2)

3.9  1.1 39 (50.0) 16.7  3.1 0.3  1.0 101.5  9.1 0.1  1.0 16.2  1.4 0.5  0.9 0.237  0.032 51 (65.4) 64 (82.1)

0.054 0.873 0.334 0.479 0.312 0.225 0.931 0.795 0.465 0.089 0.057

          

0.248 0.308 0.480 0.196 0.203 0.775 0.851 0.424 0.512 0.160 0.126

5.7 80.3 1.28 256.8 16.03 1008.5 63.01 1.73 436.2 1282.3 2.5

          

5.0 29.1 0.04 150.0 9.79 403.9 27.02 1.0 205.9 482.9 1.2

5.9 79.7 1.28 252.0 15.76 1006.2 63.98 1.7 433.5 1256.6 2.5

          

5.0 29.1 0.04 145.6 9.15 399.8 26.51 1.0 203.8 459.3 1.1

5.1 83.4 1.29 276.0 17.49 1020.8 63.14 1.6 450.5 1320.3 2.7

4.5 29.1 0.04 172.0 12.70 428.3 29.84 1.2 217.9 578.2 1.3

Note: Data are mean  standard deviation. Abbr: aBMD, areal bone mineral density; BAZ, body mass index-for-age; FFQ, food frequency questionnaire; HAZ, height-for-age; 25(OH)D, 25-hydroxyvitamin D; WAZ, weight-for-age. a Based on facultative skin type. Non-white includes Black, Hispanic, Arab, Asian, and mixed. b Includes classes I and II skin types. c 24-h dietary assessment. Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health

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Table 2 Bone Mineral Content (BMC) and Areal Bone Mineral Density (aBMD) by Age and Sex aBMD, g/cm2

BMC, g Scan pDXA forearm

cDXA forearm

cDXA lumbar spine 1e4

cDXA whole body

Age (y) 2 3 4 5 2 3 4 5 2 3 4 5 2 3 4 5

Male

0.64 0.70 0.78 0.84 10.08 11.70 13.98 16.40 490.86 579.77 701.68 799.25

           

0.12 (3) 0.06 (6) 0.11a,b (12) 0.15a,b (8) 1.99 (7) 1.89 (9) 2.44a,b (14) 2.54a,b (10) 83.46 (5) 72.12 (9) 76.27a,b (13) 115.83a,b,c (8)

Female

0.57 0.63 0.69 0.75 10.42 12.20 13.97 14.50 553.25 609.97 695.79 743.73

           

0.07 (7) 0.10 (4) 0.08 (12) 0.14 (7) 1.49 (10) 1.98 (6) 2.19 (15) 2.54 (7) 54.02 (8) 67.19 (6) 81.41a,b (15) 77.00a,b,c (7)

p value

0.996 0.999 0.436 0.301 0.993 0.999 0.999 0.173 0.986 0.900 0.999 0.529

Male 0.223 0.235 0.249 0.262 0.232 0.231 0.259 0.243 0.432 0.459 0.490 0.530 0.584 0.619 0.697 0.737

               

0.033 (68) 0.031 (77) 0.029 (79) 0.028a (33) 0.009 (3) 0.036 (6) 0.022a,b (12) 0.033a,b (8) 0.072 (7) 0.061 (9) 0.051a (14) 0.065a,b (10) 0.082 (5) 0.034 (9) 0.050a,b (13) 0.061a,b (8)

Female 0.219 0.229 0.228 0.241 0.225 0.218 0.234 0.240 0.439 0.490 0.517 0.522 0.600 0.638 0.686 0.698

               

0.034 (54) 0.029 (68) 0.033 (67) 0.029a (34) 0.029 (7) 0.015 (4) 0.029a,b (12) 0.037a,b (7) 0.041 (10) 0.068 (6) 0.067a (15) 0.062a,b (7) 0.043 (8) 0.058 (6) 0.041a,b (15) 0.044a,b (7)

p value 0.999 0.961 !0.001 0.398 0.999 0.999 0.590 0.976 0.901 0.602 0.966 0.735 0.999 0.932 0.990 0.317

Note: Numbers in parentheses represent number of children (n). Abbr: cDXA, clinical dual-energy X-ray absorptiometry; pDXA, peripheral dual-energy X-ray absorptiometry. a Greater than 2-y olds ( p ! 0.05). b Greater than 3-y olds ( p ! 0.05). c Greater than 4-y olds ( p ! 0.05).

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Vitamin D Status and BMD in Young Children mean 25(OH)D concentration was 80.3 nmol/L; only 12% (n 5 57 of 488) of the children measured fell below the IOM suggested cut-off of 50 nmol/L, although 42% fell below the CPS suggested cut-off of 75 nmol/L (n 5 203 of 488).

Bone Mineral Content Descriptive BMC data (Table 2) revealed no significant sex effects within ages for BMC at any site ( p O 0.173), although BMC at all sites were lower in 2- and 3-y olds vs other age groups (Table 2). The regression models accounted for 65% (ultradistal forearm), 70.2% (LS 1e4), and 82.1% (whole body) of the variation in BMC (Table 3). Plasma 25(OH)D as a continuous variable was associated with higher cDXA forearm BMC, although the model was improved by replacing 25(OH)D concentration with the vitamin D status classification of being above or below 75 nmol/L. Having a 25(OH)D concentration of O75 nmol/L was related to higher forearm and whole-body BMC but not higher LS 1e4 BMC.

Bone Mineral Density Descriptive aBMD data (Table 2) showed that values were higher in males vs females 4 y of age ( p ! 0.001)

5 for pDXA forearm. Values for aBMD were lower in 2- and 3-y olds vs other age groups (Table 2). The regression models (Table 4) explained 29.7% (pDXA forearm), 25.1% (cDXA forearm), 49.3% (LS 1e4), and 70.0% (whole body) of the variation in aBMD (Table 4). Plasma 25(OH)D as a continuous variable was associated with higher cDXA forearm aBMD, although the model was improved by replacing 25(OH)D concentration with the vitamin D status classification of being above or below 75 nmol/L. Having a 25(OH) D concentration of O75 nmol/L was related to higher aBMD at the forearm (pDXA and cDXA) and whole body but not LS 1e4. No indices of vitamin D, dairy consumption, calcium intake, or socioeconomic status were associated with any aBMD measures made.

PTH and iCa PTH concentrations were lower when children had a higher plasma 25(OH)D concentration (Fig. 1). Using a nonlinear regression, the relationship between PTH (0.42e 4.26 pmol/L) and 25(OH)D was statistically significant (Fig. 1, p ! 0.05). PTH was explained by the equation PTH (pmol/L) 5 1/(0.0656  25(OH)D concentration

Table 3 Multiple Linear Regressions for Variables Accounting for Bone Mineral Content (Grams) at the Ultradistal Forearm, Lumbar Spine, and Whole-Body Sites Variables cDXA ultradistal forearm (n 5 59) Age (y) HAZ WAZ Sexa Sun index (min/d) Plasma 25(OH)D O 75 nmol/Lb 2 R 5 0.650 cDXA lumbar spine 1e4 (n 5 78) Age (y) HAZ WAZ Sexa Sun index (min/d) Plasma 25(OH)D O 50 nmol/Lb 2 R 5 0.702 cDXA whole body (n 5 73) Age (y) HAZ WAZ Sexa Plasma 25(OH)D O 75 nmol/Lb 2 R 5 0.821

Regression coefficients

p values

95% Confidence intervals

Intercept 5 0.499 0.072 0.009 0.074 0.088 0.066 0.031

!0.001 0.605 !0.001 !0.001 0.029 0.036

0.050 0.042 0.039 0.129 0.001 0.010

to to to to to to

0.094 0.024 0.109 0.047 0.011 0.052

Intercept 5 4.653 1.973 0.377 1.069 0.441 0.113 0.509

!0.001 0.202 0.001 0.238 0.007 0.096

1.600 0.197 0.447 1.166 0.034 0.083

to to to to to to

2.346 0.951 1.692 0.285 0.192 1.100

Intercept 5 260.260 98.200 22.749 42.053 7.126 16.549

!0.001 0.029 0.003 0.560 0.012

85.865 2.875 21.490 30.912 4.028

to to to to to

110.295 110.295 62.541 16.676 29.016

Abbr: cDXA, clinical dual-energy X-ray absorptiometry; HAZ, height-for-age; 25(OH)D, 25-hydroxyvitamin D; WAZ, weight-for-age. a 1 5 male and 2 5 female. b 1 5 above the cut-off and 1 5 below the cut-off. Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health

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Hazell et al. Table 4 Multiple Linear Regressions for Variables Accounting for Areal Bone Mineral Density (Grams per square centimeter) at the Forearm, Lumbar Spine, and Whole-Body Sites

Variables pDXA forearm (n 5 488) Age (y) HAZ WAZ Sexa Seasonb Facultative skin typec Plasma 25(OH)D O 75 nmol/Ld 2 R 5 0.297 cDXA ultradistal forearm (n 5 59) Age (y) HAZ WAZ Sexa Facultative skin type Plasma 25(OH)D O 75 nmol/Lc 2 R 5 0.251 cDXA lumbar spine 1e4 (n 5 78) Age (y) HAZ WAZ Sexa Constitutive skin typed Plasma 25(OH)D O 50 nmol/Lc 2 R 5 0.493 cDXA whole body (n 5 73) Age (y) HAZ WAZ Sexa Sun index (min/d) Plasma 25(OH)D O 75 nmol/Lc 2 R 5 0.700

Regression coefficients

p values

95% Confidence intervals

Intercept 5 0.210 0.011 0.006 0.018 0.008 0.003 0.004 0.003

!0.001 0.003 !0.001 0.004 0.019 0.028 0.047

0.008 0.009 0.014 0.013 0.005 0.008 0.000

to to to to to to to

0.013 0.002 0.022 0.003 0.000 0.000 0.005

Intercept 5 0.240 0.007 0.001 0.012 0.008 0.014 0.007

0.028 0.862 0.033 0.185 0.033 0.041

0.001 0.009 0.001 0.020 0.027 0.001

to to to to to to

0.013 0.011 0.022 0.004 0.001 0.013

Intercept 5 0.319 0.039 0.003 0.035 0.016 0.021 0.015

!0.001 0.697 !0.001 0.143 0.029 0.098

0.028 0.021 0.016 0.005 0.039 0.003

to to to to to to

0.050 0.014 0.054 0.038 0.003 0.033

Intercept 5 0.442 0.052 0.001 0.024 0.010 0.003 0.010

!0.001 0.990 0.003 0.267 0.001 0.036

0.041 0.015 0.009 0.027 0.001 0.001

to to to to to to

0.059 0.014 0.039 0.007 0.005 0.019

Abbr: cDXA, clinical dual-energy X-ray absorptiometry; HAZ, height-for-age; 25(OH)D, 25-hydroxyvitamin D; pDXA, peripheral dualenergy X-ray absorptiometry; WAZ, weight-for-age. a 1 5 male and 2 5 female. b 0 5 spring (March 20 to June 20), 1 5 summer (June 21 to September 22), 2 5 fall (September 23 to December 21), 3 5 winter (December 22 to March 19). c 0 5 type I, 1 5 type II, 2 5 type III, 3 5 type IV, 4 5 type V, and 5 5 type VI. d 1 5 above the cut-off and 1 5 below the cut-off.

(nmol/L)  0.7372) þ 0.9578. No other variables improved the model. The pseudo R2 value (index of goodness of fit) was 0.049. Using a knot-point analysis, the plateau in PTH was w125 nmol/L 25(OH)D. iCa was not related to 25(OH)D or PTH.

Discussion This study presents novel relationships between BMC and aBMD in young children and vitamin D status that

complement previous studies in older children and adults (12,25,26). Age and WAZ positively associated with BMC in all models as did having a 25(OH)D concentration above 75 nmol/L at the forearm and whole body. Indices of vitamin D synthesis such as sun index were important at the forearm and LS 1e4 sites but less important in magnitude than age or WAZ. Based on our regression models for BMC, the benefit of having vitamin D status O75 nmol/L is equivalent to having higher WAZ of w0.5 on BMC. Important variables in models for aBMD were similar to BMC. Exogenous intake

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PTH (pmol/L)

4 3 2 1 0 0

50

100

150

200

250

25(OH)D (nmol/L)

Fig. 1. Blood biochemistrydplasma PTH concentration according to plasma 25(OH)D concentration. 25(OH)D, 25-hydroxyvitamin D; PTH, parathyroid hormone. of vitamin D was not a significant variable in accounting for BMC or aBMD at any site, which is logical because intakes did not differ over age groups, and 25(OH)D also reflects endogenous sources of vitamin D. Vitamin D status measured in this study was evaluated on the basis of plasma 25(OH)D, a relatively short-term measure. It is well accepted that the majority of 25(OH)D is derived exogenously (27). Indeed, having vitamin D intake above the RDA recommendations did not add to any of the regression models. Furthermore, neither milk servings nor total calcium intake appeared to be important to BMC or aBMD in our data. This could be a result of a high intake of milk and alternatives as the mean intake was w2.6 resulting in 74% (360 of 488) of our children meeting the recommended two servings/d. Nonetheless, plasma 25(OH)D as a continuous variable was positively linked to our cDXA forearm aBMD measurement in those children with the full assessment (n 5 78). This parallels a recent report in adults where the relationship between 25(OH)D and total hip BMD was only significant for those with concentrations below 50 nmol/L (28). However, too few (11.1%) children with whole body or regional assessments had values !50 nmol/ L. Interestingly, children with higher sun index had higher BMC at the forearm and LS 1e4 and whole-body aBMD, whereas season was only significant for pDXA forearm aBMD. Sun index was calculated over 30 d and appears to be the better proxy for longer term assessment of UVB exposure than season. However, sun index could not only relate to vitamin D status through sun exposure but also reflect another positive factor in bone health, physical activity, and thus requires further investigation. Consistent with growth patterns, age and WAZ were responsible for a significant amount of the variation in BMC and aBMD in all models, and the BMC/aBMD values strongly align with previously reported smaller studies in this age group (29,30). All BMC models accounted for greater than 65% of the variation, which is in line with previous studies in children (31). Models for regional aBMD explained

a much lower amount of variation (25%e49%), as previously observed (32), whereas the whole-body model explained 70% of the variance. With regard to sex, only the forearm (pDXA) appears to be influenced, where being male was associated with higher aBMD than being female at 4 y of age. These results agree with other research in young children which demonstrated that males had higher mid-diaphysis cortical volumetric density and thickness than girls at 6 y of age (33). The current results also agree with previous research suggesting that healthy children (0e10 y) with low 25(OH)D concentrations have higher PTH compared with children with higher vitamin status (34). A circulating 25(OH)D concentration of 125 nmol/L aligned with a plateau in PTH concentration which is higher than previous research in adolescents who would be growing more rapidly than the children in our study (35). Even though our participants were not fasted, which could explain the lower than expected PTH concentrations (many less than 1.06 pmol/L), our PTH results were consistent with fasting values in young children (34). It is more likely that the very high calcium intakes (w80% had a high calcium breakfast the day of sampling) in these children suppressed PTH as food intake, even the night before sampling, can reduce PTH (36). Even though vitamin D status was linked to bone health outcomes in our study, our sample predominantly reflected very healthy vitamin D status as the mean 25(OH)D concentration was 84 nmol/L, and only 12% (n 5 57 of 488) of values were below the IOM suggested cut-off of 50 nmol/L. Despite LS 1e4 scans being more accurate and reproducible than other regions (37), the variation in LS 1e4 was much higher (e.g. w14% of the mean) than for whole body (w9%) and may have prevented identification of relationships given our sample size. Future studies should clarify the response of bone to vitamin D intake or status using multiple measurement sites in a larger study. In conclusion, the factors involved in the endogenous synthesis of vitamin D and the composite measure of vitamin D status are important to bone in young children. The data suggest having a 25(OH)D concentration above 75 nmol/L is beneficial to BMC and aBMD as measured by DXA in young preschool-aged children, similar to older children and adults.

Acknowledgments The nursing assistance of Ms. Sandra Dell’Elce, the day care directors, and participating families are acknowledged. Funding: This research was supported by a grant from the Dairy Research Cluster under the Canadian Agri-Science Clusters Initiative of the Dairy Farmers of Canada, Agriculture and Agri-Food Canada, and the Canadian Dairy Commission.

References 1. Heaney RP, Davies KM, Chen TC, et al. 2003 Human serum 25hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77:204e210.

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Journal of Clinical Densitometry: Assessment & Management of Musculoskeletal Health

Volume

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2014

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 h...
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