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. 2008 Nov 4;94(1):67–73. doi: 10.1210/jc.2008-1575

Vitamin D Status and Its Relationship to Body Fat, Final Height, and Peak Bone Mass in Young Women

Richard Kremer 1, Patricia P Campbell 1, Timothy Reinhardt 1, Vicente Gilsanz 1
PMCID: PMC2630864  PMID: 18984659

Abstract

Context: Vitamin D insufficiency has now reached epidemic proportions and has been linked to low bone mineral density, increased risk of fracture, and obesity in adults. However, this relationship has not been well characterized in young adults.

Objective: The objective of the study was to examine the relationship between serum 25-hydroxyvitamin D (25OHD), anthropometric measures, body fat (BF), and bone structure at the time of peak bone mass.

Design: This was a cross-sectional study.

Outcome Measures and Subjects: Anthropometric measures, serum 25OHD radioimmunoassay values, and computed tomography and dual-energy x-ray absorptiometry values of BF and bone structure in 90 postpubertal females, aged 16–22 yr, residing in California were measured.

Results: Approximately 59% of subjects were 25OHD insufficient (≤29 ng/ml), and 41% were sufficient (≥30 ng/ml). Strong negative relationships were present between serum 25OHD and computed tomography measures of visceral and sc fat and dual-energy x-ray absorptiometry values of BF. In addition, weight, body mass, and imaging measures of adiposity at all sites were significantly lower in women with normal serum 25OHD concentrations than women with insufficient levels. In contrast, no relationship was observed between circulating 25OHD concentrations and measures of bone mineral density at any site. Unexpectedly, there was a positive correlation between 25OHD levels and height.

Conclusions: We found that vitamin D insufficiency is associated with increased BF and decreased height but not changes in peak bone mass.

Vitamin D insufficiency in young women is associated with increased body fat and decreased height.

Vitamin D, a key regulator of bone metabolism, is thought to play an important role in adipogenesis and the prevention of a variety of diseases, including osteoporosis, cancer, diabetes, and immune disorders (1,2,3). It is derived from skin exposure to sunlight (vitamin D3) or food supplements (vitamins D2 or D3) and undergoes successive hydroxylations in the liver and kidneys to give rise to its active metabolite 1α,25 dihydroxyvitamin D (4). The vitamin D receptor is widely distributed in various tissues including bone and fat and triggers most of the action of vitamin D (5). There are, however, significant discrepancies in the results of previous studies assessing the relation between vitamin D, bone health, and adiposity.

Whereas several studies in adults have shown that vitamin D increases bone mineral density (BMD) (6), prevents osteoporotic fractures (7,8), and reduces the risk of falling in the elderly (9), other studies in adolescents and young adults have yielded conflicting results; some, but not all, found an association between vitamin D and bone mass (10,11,12,13,14,15). Moreover, a recent study in adults aged 30–79 yr suggests the relation between 25-hydroxyvitamin D (25OHD) levels and BMD is present in the white population but not African-Americans or subjects of Hispanic ethnicity (16).

Obesity has now reached epidemic proportions, and the combined percentage of overweight and obese individuals in the United States is staggering, approaching 32% in children and adolescents and 66% in young adults (17). Although vitamin D insufficiency is prevalent in this population, especially in low socioeconomic groups (18,19), limited information regarding the relationship between weight and vitamin D levels is available. Several studies have shown adult obesity to be inversely correlated with 25OHD levels (20,21,22,23,24,25,26), and it has been suggested that adipogenesis may be inhibited by 1α,25 dihydroxyvitamin D (27). Even obese adults who take supplemental vitamin D2 and are exposed to UV light have 25OHD levels substantially lower than nonobese matched controls (24).

Discrepancies in the results from previous studies may, in part, be related to the use of dual-energy x-ray absorptiometry (DXA) to obtain bone and/or fat measures because this projection technique cannot correct for the influence of other soft tissues in the region of interest (28). In this investigation, to account for the influence of soft tissues on DXA bone measurements, we examined the relations between vitamin D, bone health, and adiposity by using both DXA and computed tomography (CT). Additionally, the confounding effects of growth and development, aging, and gender on the relations between fat mass, bone mass, and vitamin D were controlled by including only sexually and skeletally mature young females aged 16–22 yr.

Subjects and Methods

Study subjects

This study was approved by the institutional review board at our institution, and informed consent was obtained from all parents and/or subjects. An initial interview was conducted to describe the purpose and aims of the study and the tests to be performed. Candidates for this study were excluded if they had a diagnosis of any underlying disease or chronic illness, if they had been ill for longer than 2 wk during the previous 6 months, if they had been admitted to the hospital at any time during the previous 3 yr, or if they were taking any medications including oral contraceptives. Candidates who were pregnant, had ever been pregnant, or with absence of menses for more than 4 consecutive months were also excluded from the study. To decrease the seasonal variability in biochemical determinations, all appointments were scheduled between May and October. In addition, all subjects had normal kidney function and normal liver function tests, and there was no evidence of liver abnormalities detected by CT.

All potential participants underwent a general physical examination, including assessments of the degree of sexual development, and a radiographic examination of the left hand and wrist. Only those who had reached sexual maturity, defined as Tanner V of breast development (29), and skeletal maturity, defined as epiphyseal closure in the phalanges and metacarpals using the radiographic atlas of Greulich and Pyle (30), were included in the study. Measurements of weight were obtained to the nearest 0.1 kg, using the Scale-Tronix (Scale-Tronix, Inc, Wheaton, IL), and measurements of height were obtained to the nearest 0.1 cm, using the Harpenden stadiometer (Holtain Ltd., Crymmych, Wales, UK). Body mass index (BMI) was calculated as weight (kilograms) divided by height squared (square meters); for the purpose of this study, subjects were divided into a lean group (BMI < 25 kg/m2) and an overweight group (BMI ≥ 25 kg/m2). Using this approach, 90 female subjects were enrolled in this study and underwent imaging determinations of bone and adipose tissue and biochemical measurements of calcium-regulating hormones.

Bone and fat measurements

DXA and CT determinations of bone and fat were performed on the same day by the same technologist. Using a Hologic QDR4500 DXA scanner (Hologic, Inc., Bedford, MA), the bone mineral content (BMC; grams) and the BMD (grams per square centimeter) were measured for the total body and for the axial and appendicular skeleton independently. In addition, the total, subtotal (excluding the head), arms, trunk, and leg fat mass (kilograms) were determined. The coefficients of variation (CVs) for repeated DXA measurements of BMC, BMD, and fat mass at the various locations examined have been reported to range from 0.7 to 4.1%, and the radiation exposure is negligible (31).

For CT determinations, a Hilite Advantage scanner (General Electric Healthcare, Milwaukee, WI) with a standardized reference phantom for simultaneous calibration was used. In the axial skeleton, values for cancellous bone density (milligrams per cubic centimeter) and the cross-sectional area (CSA; square centimeters) were measured at the midportion of the first three lumbar vertebral bodies, and in the appendicular skeleton, the CSA (square centimeters), cortical bone area (square centimeters), and cortical bone density (milligrams per /cubic centimeter) at the midshafts of the femurs were obtained; CVs for these bone measurements in young adults were previously reported between 0.6 and 1.5% (32). Additionally, from the same cross-sectional abdominal images measurements of the visceral fat (square centimeters) and sc fat (square centimeters) were obtained. For the purpose of this study, sc fat was defined as the amount of adipose tissue located between the skin and the rectus muscles of the abdomen, the external oblique muscles, the broadest muscles of the back, and the erector muscles of the spine at the level of the umbilicus. Visceral fat was defined as the intraabdominal adipose tissue surrounded by the rectus muscles of the abdomen, the external oblique muscles, the lumbar quadrate muscle, the psoas muscles, and the lumbar spine at the same level. The CV for repeated measures of visceral and sc fat has been reported to range from 1.5 to 3.5% (33). The time to complete the CT scans was approximately 10 min and the effective radiation dose was approximately 0.1 mSv (34).

Biochemical determinations

Serum levels of 25OHD were assayed using a RIA as described by Hollis et al. (35). The lower limit of detection was 5 ng/ml (12.5 nmol/liter). Goat anti-25OHD was a gift from Dr. Bruce Hollis (Medical University of South Carolina, Charleston, SC). 125I-25-hydroxy-vitamin D3 and donkey antigoat secondary antibody were purchased from Diasorin (Stillwater, MN). This assay recognizes equally serum 25-hydroxy-vitamin D2 and serum 25-hydroxy-vitamin D3 and shows no bias when compared with HPLC (36). Calculated assay precision for within-assay variation averages 6% and for interassay 16%. For the purpose of this study and according to the current consensus, subjects were divided into a 25OHD sufficient, or normal, group (≥30 ng/ml) and an insufficient group (≤29 ng/ml). Intact PTH (1–84) was measured with an electrochemiluminescent assay (37). The sensitivity of the assay is 1.2 pg/ml (0.127 pmol/liter) and intra- and interassay variations are 1.9–4 and 2.6–6.5%, respectively. To minimize interassay variability, all samples were analyzed simultaneously.

Statistical analysis

A sample size of 90 subjects allows the determination of correlations greater than r = .28 with 80% power. Statistical analysis was carried out using Statview (version 5.0.1; SAS Institute Inc., Cary, NC). Data were analyzed using simple linear regression analysis, multiple regression analysis, and unpaired t tests. All values are expressed as mean ± sd.

Results

Relation between 25OHD and subject characteristics

The age, anthropometric characteristics, and ethnic background of the women studied are described in Table 1. Weight and BMI were significantly higher, whereas height was significantly lower, in Hispanics than Caucasians. When all subjects were taken together, a significant positive correlation was found between height and 25OHD (Fig. 1). In contrast, significant negative correlations were observed between 25OHD, weight, and BMI (Fig. 1). Multiple regression analysis showed that the negative relation between 25OHD and weight and the positive relation between 250HD and height persisted, even after accounting for differences in ethnic background.

Table 1.

Age and anthropometric characteristics of 90 women separated by ethnic background

All (n = 90) Hispanic (n = 53) Caucasian (n = 37) P
Age (yr) 19.4 ± 1.5 (16.3–22.8) 19.6 ± 1.4 (17.0–22.8) 19.1 ± 1.6 (16.3–22.2) 0.100
Weight (kg) 68.3 ± 17.5 (45.5–126.0) 72.7 ± 20.5 (45.5–126.0) 61.9 ± 8.8 (45.6–90.3) 0.003
Height (cm) 162.9 ± 4.7 (153.9–171.8) 161.6 ± 4.7 (153.9–171.8) 164.8 ± 4.1 (156.3–170.8) 0.001
BMI 25.7 ± 6.3 (16.7–44.5) 27.7 ± 7.1 (17.6–44.5) 22.8 ± 3.5 (16.7–35.6) <0.001
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Values are expressed as mean ± sd and (range). P values indicate results of unpaired t tests between ethnic backgrounds. 

Figure 1.

Figure 1

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Relation between vitamin D concentrations and height, weight, and BMI. Cau, Caucasian; Hisp, Hispanics.

Table 2 shows the mean values for 25OHD concentrations in lean (BMI < 25 kg/m2) and overweight (BMI ≥25 kg/m2) subjects. Whereas mean serum values were significantly lower in Hispanics than Caucasians, ethnic differences in 25OHD concentrations did not persist after adjusting for BMI (Table 2).

Table 2.

25OHD concentrations (nanograms per milliliter) of 90 women separated by ethnicity and body mass

25OHD (ng/ml)
All (n = 90) Hispanic (n = 53) Caucasian (n = 37)
All BMI (n = 90) 30.1 ± 13.0 (6.7–69.6) 26.6 ± 12.3a,b (6.7–67.3) 35.1 ± 12.4 (14.2–69.6)
Lean (BMI < 25 kg/m2) (n = 51) 34.3 ± 13.8c (15.2–69.6) 31.2 ± 14.6 (15.2–67.3) 36.6 ± 12.9 (16.1–69.6)
Overweight (BMI ≥ 25 kg/m2) (n = 39) 24.6 ± 9.5 (6.7–46.0) 23.3 ± 9.3 (6.7–44.9) 29.7 ± 9.3 (14.2–46.0)
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Values are expressed as mean ± sd and (range). 

a

Indicates a significant difference between Hispanics and Caucasians (P = 0.002). 

b

ANOVA analysis indicates no statistical difference between Hispanics and Caucasians when adjusted for BMI (P = 0.09). 

c

Indicates a significant difference between lean and overweight subjects (P < 0.001). 

Thirty-seven women (41%) had normal 25OHD concentrations (≥30 ng/ml), whereas 53 women (59%) had insufficient 25OHD concentrations (≤29 ng/ml); of the insufficient group, 24 (45%) had values 20 ng/ml or less. Compared with women with normal 25OHD values, vitamin D-insufficient subjects were of identical age but were significantly shorter and heavier and had greater BMI (Table 3). When the sufficient group was analyzed independently, no associations were present between vitamin D and any anthropometric measures. In contrast, there were significant negative correlations between 25OHD and both weight and BMI (r = −0.28 and −0.33, respectively; P = 0.045 and 0.015, respectively) in the insufficient group.

Table 3.

25OHD values, age, and anthropometric characteristics of 90 women separated by 25OHD concentration groups

All (n = 90) Sufficient (n = 37) Insufficient (n = 53) P values
25OHD (ng/ml) 30.1 ± 13.0 (6.7–69.6) 42.4 ± 10.1 (30.0–69.6) 21.5 ± 5.9 (6.7–29.6) <0.001
Age (yr) 19.4 ± 1.5 (16.3–22.8) 19.2 ± 1.6 (16.3–22.8) 19.5 ± 1.4 (17.0–22.87) 0.408
Weight (kg) 68.3 ± 17.5 (45.5–126.0) 63.9 ± 11.9 (45.6–113.0) 71.3 ± 20.0 (45.5–126.0) 0.046
Height (cm) 162.9 ± 4.7 (153.9–171.8) 164.1 ± 3.9 (156.8–170.3) 162.1 ± 5.1 (153.9–171.8) 0.048
BMI (kg/m2) 25.7 ± 6.3 (16.7–44.5) 23.7 ± 4.6 (16.7–43.9) 27.1 ± 7.1 (17.6–44.5) 0.014
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Values are expressed as mean ± sd and (range). P values indicate results of unpaired t test between 25OHD concentration groups. 

A significant inverse correlation was found between 25OHD and PTH (r = −0.27; P = 0.01), and PTH values were higher in the insufficient than the sufficient group (2.28 ± 0.88 and 1.92 ± 0.90, respectively; P = 0.025).

Relation between 25OHD and imaging measures of body fat and bone

CT measures for sc and visceral fat and DXA measurements for whole-body fat, truncal fat, and upper and lower extremity fat were significantly lower in women with normal 25OHD concentrations than women with insufficient 25OHD (Table 4). In contrast, there were no differences in CT or DXA values for bone in the axial and appendicular skeleton between women with sufficient and those with insufficient 25OHD concentrations (Table 4).

Table 4.

CT and DXA fat and bone measurements in 90 women separated by 25OHD concentration groups

All (n = 90) Sufficient (n = 37) Insufficient (n = 53) P
Fat phenotypes
 CT
  Subcutaneous (cm2) 252.8 ± 152.7 203.3 ± 98.9 288.1 ± 174.0 0.029
  Visceral (cm2) 36.46 ± 42.89 24.74 ± 33.88 44.81 ± 46.83 0.009
 DXA
  Total (kg) 24.81 ± 11.79 21.59 ± 7.67 27.10 ± 13.62 0.029
  Trunk (kg) 11.29 ± 5.76 9.35 ± 3.82 12.69 ± 5.61 0.006
  Arms (kg) 1.64 ± 1.02 1.34 ± 0.61 1.85 ± 1.19 0.019
  Legs (kg) 4.75 ± 1.91 4.33 ± 1.38 5.05 ± 2.17 0.077
Bone phenotypes
 CT
  Vertebral BD (mg/cm3) 299.1 ± 43.5 294.4 ± 37.3 302.5 ± 47.5 0.392
  Vertebral CSA (cm2) 8.78 ± 1.32 8.73 ± 1.21 8.83 ± 1.40 0.723
  Femoral CBD (mg/cm3) 1234 ± 36 1236 ± 37 1233 ± 37 0.763
  Femoral CBA (cm2) 4.23 ± 0.53 4.24 ± 0.39 4.23 ± 0.61 0.955
  Femoral CSA (cm2) 5.11 ± 0.72 5.07 ± 0.57 5.14 ± 0.81 0.649
 DXA
  Total BMC (g) 2105 ± 298 2110 ± 272 2101 ± 317 0.886
  Total BMD (g/cm2) 1.11 ± 0.07 1.11 ± 0.08 1.11 ± 0.07 0.919
  Trunk BMC (g) 168.0 ± 26.9 161.8 ± 19.3 172.5 ± 30.6 0.771
  Trunk BMD (g/cm2) 0.88 ± 0.07 0.88 ± 0.07 0.88 ± 0.08 0.884
  Hip BMC (g) 39.56 ± 6.16 40.19 ± 4.95 39.12 ± 6.90 0.421
  Hip BMD (g/cm2) 1.05 ± 0.11 1.05 ± 0.08 1.04 ± 0.13 0.663
  Arm BMC (g) 138.8 ± 23.9 137.8 ± 18.0 139.5 ± 27.4 0.933
  Arm BMD (g/cm2) 0.73 ± 0.06 0.74 ± 0.06 0.73 ± 0.06 0.446
  Leg BMC (g) 389.9 ± 62.7 392.8 ± 50.4 387.8 ± 70.5 0.715
  Leg BMD (g/cm2) 1.17 ± 0.09 1.17 ± 0.08 1.16 ± 0.10 0.586
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P-values indicate results of unpaired t test between 250HD concentration groups. CBD, Cortical bone density; BD, bone density. 

Regardless of imaging technique, strong negative correlations were observed between all measures of body adiposity and 25OHD at all sites (Table 5). These associations were present when all women were considered together and when 25OHD-insufficient subjects were analyzed independently (Table 5); this relation was not present in women with sufficient 25OHD. In contrast, regardless of whether all subjects were taken together or were separated by 25OHD concentration group, no significant association was found between 25OHD levels and any DXA or CT bone phenotypes (data not shown).

Table 5.

Relations between 25OHD concentrations and imaging measures of fat and bone in 90 women

Fat phenotypes All (n = 90)
Sufficient (n = 37)
Insufficient (n = 53)
r P r P r P
CT
 sc −0.36 <0.001 −0.19 0.261 −0.32 0.019
 Visceral −0.28 0.007 −0.05 0.769 −0.30 0.031
DXA
 Total −0.32 0.002 −0.18 0.303 −0.32 0.022
 Trunk −0.37 <0.001 −0.16 0.333 −0.35 0.011
 Arms −0.29 0.006 −0.16 0.204 −0.33 0.025
 Legs −0.33 0.001 −0.22 0.342 −0.31 0.016
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Discussion

We found a strong inverse correlation between weight and body mass and circulating vitamin D and that young women with vitamin D insufficiency were significantly heavier and had greater body mass than women with normal levels. Additionally, the results of this study showed significant reciprocal relations between 25OHD and CT measures for sc and visceral fat and DXA measures of adiposity for the whole body, trunk, and extremities. The high prevalence of vitamin D insufficiency in this young population living in a sun-rich area is surprising and likely multifactorial. A recent report indicates that vitamin D insufficiency is common in children aged 6–21 yr living in the northeastern United States and is associated with season, ethnicity/black race, age, and vitamin D intake (18), but similar observations have not yet been reported in California. Whereas vitamin D insufficiency was more common in Hispanics than Caucasians in our study cohort, this difference did not persist after adjusting for BMI, indicating that the predominant risk factor was body fat rather than any variability in skin color attributed to ethnicity.

In view of the prevalence of both vitamin D insufficiency and obesity in children and adolescents, it is possible that vitamin D status is an independent predictor of weight gain. Several studies in the adult population suggest that obesity is associated with vitamin D insufficiency (20,21,22,23,24,26,38), and one indicates that low vitamin D intake is an independent predictor of obesity (25). Another investigation in postmenopausal women receiving calcium plus vitamin D reported a small effect on weight gain prevention compared with placebo (39). Indeed, vitamin D has been shown to lower leptin concentrations and may therefore contribute to the maintenance of body mass (40). On the other hand, body fat may also contribute to low circulating vitamin D levels by trapping vitamin D in fat tissues (24). Thus, obesity may, in part, be a direct consequence of vitamin D insufficiency and/or may result in vitamin D insufficiency. It is noteworthy that vitamin D insufficiency has been implicated in numerous health conditions including osteoporosis, cancer, diabetes, and rheumatoid arthritis (1,2,41) and that increased body fat is also strongly associated with greater risk of diabetes and cancer (42). Consequently, vitamin D insufficiency may play an important role in the development of these various clinical conditions either directly or indirectly.

In addition to weight and body mass, we specifically determined fat content and fat distribution using DXA and CT. Previously, using bioelectrical impedance analysis in a large group of women of all ages, indirect measures of the percentage of body fat were found to be inversely related to circulating 25OHD; an association that was particularly noticeable in white females aged 12–49 yr (38). Another study using DXA also found a negative correlation between 25OHD and percentage of body fat, but not BMI, in healthy adult women (22). The current study extends these findings to a young population of white females and indicates a strong inverse correlation between body fat and 25OHD using total-body measurements by DXA and site-specific measurements by CT. Our data indicate that 25OHD is inversely correlated with not only total body fat but also specific measures of visceral fat and sc fat, suggesting that this relationship is independent of the site of fat accumulation.

Unexpectedly, there was a positive correlation between circulating 25OHD and height in the population studied. Whereas vitamin D is key to skeletal development and its deficiency may result in short stature associated with rickets (15), none of the subjects in this study had any clinical or radiological evidence of rickets. A significant decrease in height was previously reported in adolescent girls aged 13–17 yr who had vitamin D deficiency without any clinical evidence of rickets (10). Further studies are needed to determine the possible role of vitamin D in longitudinal bone growth in the absence of clinical evidence of rickets.

An intriguing result of this study was the absence of a correlation between vitamin D status and bone determinations, regardless of site or whether assessed by DXA or CT. Previous investigations in adults indicated that vitamin D supplementation improved BMD and reduced the risk of osteoporosis and fractures (6,7,8,14). However, studies in adolescent females yielded discrepant results; some reported an association between low bone mass and vitamin D insufficiency and low vitamin D intake (12,13), whereas others, like ours, found no such relation (10,11). Although our population was comprised of Hispanics and Caucasians, this study was not powered to analyze Caucasians and Hispanics separately, and the possibility of ethnic variability in the response to vitamin D exposure cannot be excluded. Similarly, our findings in females do not exclude the notion that vitamin D influences bone mass in adolescent and young adult males, as previously reported (43,44). Despite these limitations, the results of the current study support the hypothesis that the negative effect of vitamin D insufficiency on bone mass may not be present in healthy young adults around the time that bone mass reaches its peak.

The use of two techniques for the accurate and independent assessment of the relations of vitamin D to bone and fat tissue, the use of the same technologist to obtain all CT and DXA measures and the rigorous assessment of the sexual and skeletal development, is a major strength of this study. Previous studies on the effects of vitamin D insufficiency on bone were mostly conducted using DXA, a technique that is low in cost, has minimal radiation exposure, and is readily accessible and easy to use.

Although DXA values are influenced by changes in body configuration (28,45,46) and inherently underestimate bone acquisition in short and/or overweight individuals (47), it should be noted that despite these limitations, our findings were similar, regardless of technique.

In conclusion, our study indicates that vitamin D insufficiency is extremely common in young women living in a sun-rich area of the United States. It also supports the hypotheses that either vitamin D insufficiency is a risk factor for increased body fat or increased body fat is a risk factor for vitamin D insufficiency. The positive association between height and vitamin D status is unexplained and intriguing and warrants further investigation. Our data, however, do not support a role for vitamin D in regulating bone mass acquisition around the time it reaches its peak.

Footnotes

This work was supported by the Department of the Army (DAMD17-01-1-0817), the National Institutes of Health (1R01 AR052744-01), and Natural Sciences and Engineering Research Council and Dimensional Fund Advisors Canada.

Disclosure Summary: R.K., P.P.C., T.R., and V.G. have nothing to declare.

First Published Online November 4, 2008

Abbreviations: BMC, Bone mineral content; BMD, bone mineral density; BMI, body mass index; CSA, cross-sectional area; CT, computed tomography; CV, coefficient of variation; DXA, dual-energy x-ray absorptiometry; 25OHD, 25-hydroxyvitamin D.

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