Vitamin-D receptor genotype does not predict bone mineral density, bone turnover, and growth in prepubertal children.

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Abstract

We examined whether the polymorphism for BsmI restriction enzyme in the vitamin-D receptor (VDR) gene influenced radial (distal third) and lumbar (L2-L4) bone mineral density (BMD), phospho-calcium metabolism (calcium, phosphate, intact parathyroid hormone, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D), biochemical markers of bone formation (osteocalcin and carboxy-terminal propeptide of type-I procollagen) and bone resorption (carboxy-terminal telopeptide of type-I collagen and urinary cross-linked N-telopeptides of type I collagen), insulin-like growth factor I and insulin-like growth factor-binding protein 3, and growth in 209 healthy prepubertal children (112 males and 97 females) aged 7.1-10.0 years. Genotype frequencies were BB 19%, Bb 46%, and bb 35% in the pooled group of children. Clinical findings, dietary calcium intake, calcium density, and physical activity rate were not different (p NS) among the VDR genotypes. Radial BMD, lumbar BMDarea and lumbar BMD adjusted for the apparent bone volume (BMDvolume), and all the biochemical parameters did not differ (p NS) in relation to the VDR genotype. In conclusion, our data show that polymorphism for BsmI restriction enzyme in the VDR gene is not associated with radial and lumbar BMD, parameters of phospho-calcium metabolism and bone turnover, growth hormone-dependent growth factors, and growth in prepubertal children.

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Comparison of different models for interpreting bone mineral density measurements using DXA and MRI technology.

H Kröger, P Vainio, J. Nieminen … (1995)

Bone mineral density measurements using dual X-ray absorptiometry (DXA) are commonly expressed as areal density (g/cm2). However, areal BMD (BMDareal) is dependent on bone size and this can lead to erroneous interpretations of BMD values. We have previously presented a simple method for calculating apparent volumetric bone mineral density (BMDvol) using ancillary DXA-derived data. In the present study we tested the validity of our model using in vivo volumetric data obtained from magnetic resonance imaging (MRI) of lumbar vertebrae. BMDareal and BMDvol of L3 were measured from sixteen pairs of identical twins (24 men, 8 women), aged 25-69 years. The dimensions of the lumbar vertebra L3 were measured from MR images and BMD values were corrected for these dimensions. The DXA-derived apparent volumetric bone mineral density (BMDvol) correlated moderately with MRI-derived BMDs (r values from 0.665 to 0.822). In contrast to BMDareal, BMDvol and MRI-derived BMDs were not related to body size variables. All these volume-corrected BMDs diminished the erroneous effect of vertebral size on areal BMD. We conclude that the simple DXA-derived BMDvol can be used for normalization of bone mineral density values in subjects of different body sizes, and especially in growing children.

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Vitamin D-receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent.

J Sayre, V Loro, Åsmund T. Røe … (1997)

Bone mass is under strong genetic control, and recent studies in adults have suggested that allelic differences in the gene for the vitamin D receptor may account for inherited variability in bone mass. We studied the relations of the vitamin D-receptor genotype to skeletal development and variation in the size, volume, and density of bone in children. We identified three allelic variants of the vitamin D-receptor gene using the polymerase chain reaction and three restriction enzymes (ApaI, BsmI, and TaqI) in 100 normal prepubertal American girls of Mexican descent. We then determined the relations of the different vitamin D-receptor genotypes (AA, Aa, aa, BB, Bb, bb, TT, Tt, and tt) to the cross-sectional area, cortical area, and cortical bone density of the femoral shaft and the cross-sectional area and density of the lumbar vertebrae. The vitamin D-receptor genotype was associated with femoral and vertebral bone density. Girls with aa and bb genotypes had 2 to 3 percent higher femoral bone density (P=0.008 and P=0.04, respectively) and 8 to 10 percent higher vertebral bone density (P=0.01 and P=0.03, respectively) than girls with AA and BB genotypes. There was no association between the cross-sectional area of the vertebrae or the cross-sectional or cortical area of the femur and the vitamin D-receptor genotype. The chronologic age, bone age, height, weight, body-surface area, and body-mass index did not differ significantly among girls with different vitamin D-receptor genotypes. Vitamin D-receptor gene alleles predict the density of femoral and vertebral bone in prepubertal American girls of Mexican descent.