JOURNAL OF BONE AND MINERAL RESEARCH Volume 10, Number 9, zyxwvutsrqp 1995 Blackwell Science, Inc. zyxwvutsrqpon Vitamin D Receptor Gene Polymorphisms Do Not Predict Bone Turnover and Bone Mass in Healthy Premenopausal Women PATRICK CiARNERO, OLIVIER BOREL, ELIZABETH SORNAY-RENDU, and PIERRE D. DELMAS ABSTRACT Bone mineral density (BMD) is under strong genetic control. Polymorphisms at the vitamin D receptor (VDR) gene have been recently suggested to account for up to 75% of this genetic effect. We analyzed these polymor- phisms, i.e., that of zyxwvutsrq BsrnI, TuqI, and ApaI restriction enzymes by PCR of the DNA in 189 healthy premenopausal women aged 31 to 57 years. For the BsmI polymorphism they were 17% BB homozygotes, 51% Bb heterozygotes, and 32% bb homozygotes, genotype frequencies that are very similar to those previously reported in other Caucasian populations of north European ancestry. Women in the three genotypes for any of the three polymor- phisms were matched for age and did not differ in body weight, height, physical activity, nor smoking habits. We found no relationship between the genotype for any of the three polymorphisms nor bone formation and resorption rate assessed by five specific biochemical markers of bone turnover nor with BMD measured at the spine, proximal femur, forearm, and whole body by dual-energy X-ray absorptiometry (DXA). We concluded that these polymor- phisms are not predictive of bone turnover nor BMD in a sample of healthy premenopausal women drawn from the French population. (J Bone Miner Res 1995;101283-1288) INTRODUCTION LOW PEAK BoNE zyxwvutsrqponml MASS achieved in adulthood is a major A determinant of reduced bone density, which is respon- sible for osteoporotic fractures. Peak bone mass is strongly inherited, and twin studies suggest that genetic factors ac- count for up to 80% of bone mineral density (BMD) vari- ance in young adults.('-3) Kelly et al.(4) and Tokita et aLC5) have shown a genetic influence on serum osteocalcin and propeptide of type I collagen (PICP), two markers of bone formation, suggesting that the genetic control of peak bone mass is mediated through genetic effects on bone turnover. Recently, Morisson et a1.(6) claimed that polymorphisms at the vitamin D receptor (VDR) gene could be responsible for up to 75% of the total genetic effect on peak bone mass and that genotyping could be used to predict a predisposi- tion to osteoporosis. These authors reported that homozy- gote twins for the VDR gene alleles defined by the restric- tion enzyme zyxwvutsrqpon BsmI differed by about 16% in lumbar spine BMD, i.e., more than one standard deviation (SD of the normal population. Among unrelated women, the fracture threshold (defined as 2 SD below the mean peak bone mass of young adults) was reached 18.4 years after menopause in the BB subjects (without BsmI sites on the two VDR gene alleles) versus 29 years in the bb females, suggesting that the b allele is associated with higher bone mass. Recently, Ferrari et al.") suggested that these polymorphisms could also predict the rate of spinal bone change in the elderly. However, an association between allelic variations in the VDR gene and BMD has been a subject of controversies, some studies('-"') confirming the results of Morisson et al.,(") others finding no relationship between BMD and VDR gene aIIeIes.(' '-I3) In this study we examined the relationships between VDR genotypes on the one hand and both the bone turn- over rate assessed by new specific and sensitive biochemical markers and the BMD measured at several sites on the other hand in a population of healthy unrelated premeno- pausal women. INSERM unit 403, HBpital 1 : . Herriot, Lyon, France. 1283