DETERMINANTS OF PREMENOPAUSAL BONE-MINERAL DENSITY - THE INTERPLAY OFGENETIC AND LIFE-STYLE FACTORS

Bone mineral density (BMD) is a reflection of both genetic and lifesty le factors. The interplay of genetic (vitamin D receptor [VDR] gene po lymorphisms) and lifestyle factors on BMD at the lumbar spine and prox imal femur was examined in 470 healthy premenopausal women, aged 44-50 years, using a Hologic QDR 2000 densitometer. The objective of this s tudy was to examine the genetic and lifestyle determinants of premenop ausal BMD. Each participant was genotyped for BsmI polymorphism at the VDR gene locus. The presence of a restriction site within VDR, specif ied as bb (189, 40.2%) (n, %) was associated,vith reduced spinal BMD, whereas absence of this site in BE (97, 20.6%) conferred greater spina l BMD, as did the genotype Bb (184, 39.1%). Associations between smoki ng, alcohol use, oral contraceptives, education level, multivitamins, number of children, degree of obesity, body weight, physical activity, dietary calcium intake, and VDR genotype to BMDs were examined. VDR g enotype, body weight, degree of obesity, physical activity, and dietar y calcium intake were all significant determinants of BMD. The associa tion of VDR genotype,vith BMD at the femoral neck appeared to be modif ied by calcium intake (BE and Bb: 0.797 +/- 0.11 g/cm(2) vs. 0.844 +/- 0.11 g/cm(2), interaction term,p = 0.06) for low (<1036 mg/day) and h igh (greater than or equal to 1036 mg/day; upper quartile) calcium int akes, respectively. A similar trend was demonstrated for physical acti vity. These findings suggest that prophylactic interventions aimed at achieving and maintaining optimal BMD, such as greater calcium intake or physical activity, may be important in maximizing one's genetic pot ential for BMD.