DO DIETARY CALCIUM AND AGE EXPLAIN THE CONTROVERSY SURROUNDING THE RELATIONSHIP BETWEEN BONE-MINERAL DENSITY AND VITAMIN-D-RECEPTOR GENE POLYMORPHISMS

Whether vitamin D receptor (VDR) gene polymorphisms are associated wit h osteoporosis is highly controversial. The relationship between VDR g ene polymorphisms and bone mineral density (BMD) might, however, be mo dified by age-related and/or environmental factors. We studied the pot ential association between BMD and VDR genotypes in females from prepu berty to premenopause and prospectively investigated the interaction o f VDR genotypes with dietary calcium and BMD changes during childhood. Bsm I VDR gene polymorphisms and BMD at the lumbar spine (LS) and fem ur (neck [FN] and midshaft [FS]) were assessed in 369 healthy Caucasia n females, aged 7-56 years (143 prepubertal girls, 54 peri-and postpub ertal adolescents, and 172 premenopausal adults). Femoral trochanter ( FT) and distal radius BMD (metaphysis and diaphysis) were also measure d in 101 of the prepubertal girls who participated in a 1-year, double -blind, randomized study of calcium supplementation (850 mg/day) versu s placebo on bone mineral mass accrual. Among all females, 150 (40.7%) had bb, 167 (45.3%) Bb, and 52 (14%) BB VDR genotypes. In prepubertal and adolescent girls altogether, LS BMD (Z scores) was associated wit h VDR genotypes and was significantly lower in BB than in Bb or bb sub jects. Trends for a similar difference were also detected at the FN le vel as well as on the mean BMD (Z scores) of the three sites measured (LS, FN, and FS). By contrast, no BMD differences were detectable amon g VDR genotypes in the adults. in 101 prospectively studied prepuberta l girls, calcium supplementation significantly increased BMD at most s keletal sites, except LS. After segregation for VDR genotypes (40 bb, 47 Bb, and 14 BB), a significant calcium effect was present in Bb but not bb girls, whereas in BB girls there was a positive but nonsignific ant trend for a calcium effect. Moreover, dietary calcium intake was s ignificantly correlated with BMD changes at various independent bone s ites in Bb girls but not in bb girls. In contrast, BMD gain in bb girl s appeared to be higher than among the other genotypes when the dietar y calcium intake was low, i.e., in the absence of calcium supplements. BMD was significantly associated with VDR gene polymorphisms only bef ore puberty, BB girls having significantly lower BMD (Z scores) than t he other genotypes. By increasing dietary calcium intake, BMD accrual was increased in Bb and possibly BB prepubertal girls, whereas bb subj ects had the highest spontaneous BMD accrual and remained unaffected b y calcium supplements. Taking into account complex interactions betwee n VDR gene polymorphisms and environmental factors, including calcium intake, may thus help to understand the discordant relationships betwe en BMD and VDR gene polymorphisms.