Ferrari S L, Rizzoli R, Slosman D O, Bonjour J P
WHO Collaborating Center for Osteoporosis and Bone Diseases, Department of Internal Medicine, University Hospital, Geneva, Switzerland.
J Bone Miner Res. 1998 Mar;13(3):363-70. doi: 10.1359/jbmr.1998.13.3.363.
Whether vitamin D receptor (VDR) gene polymorphisms are associated with osteoporosis is highly controversial. The relationship between VDR gene polymorphisms and bone mineral density (BMD) might, however, be modified by age-related and/or environmental factors. We studied the potential association between BMD and VDR genotypes in females from prepuberty to premenopause and prospectively investigated the interaction of VDR genotypes with dietary calcium and BMD changes during childhood. Bsm I VDR gene polymorphisms and BMD at the lumbar spine (LS) and femur (neck [FN] and midshaft [FS]) were assessed in 369 healthy Caucasian females, aged 7-56 years (143 prepubertal girls, 54 peri- and postpubertal adolescents, and 172 premenopausal adults). Femoral trochanter (FT) and distal radius BMD (metaphysis and diaphysis) were also measured in 101 of the prepubertal girls who participated in a 1-year, double-blind, randomized study of calcium supplementation (850 mg/day) versus 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 with VDR genotypes and was significantly lower in BB than in Bb or bb subjects. Trends for a similar difference were also detected at the FN level 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 among VDR genotypes in the adults. In 101 prospectively studied prepubertal girls, calcium supplementation significantly increased BMD at most skeletal 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 nonsignificant trend for a calcium effect. Moreover, dietary calcium intake was significantly correlated with BMD changes at various independent bone sites in Bb girls but not in bb girls. In contrast, BMD gain in bb girls appeared to be higher than among the other genotypes when the dietary calcium intake was low, i.e., in the absence of calcium supplements. BMD was significantly associated with VDR gene polymorphisms only before puberty, BB girls having significantly lower BMD (Z scores) than the other genotypes. By increasing dietary calcium intake, BMD accrual was increased in Bb and possibly BB prepubertal girls, whereas bb subjects had the highest spontaneous BMD accrual and remained unaffected by calcium supplements. Taking into account complex interactions between VDR gene polymorphisms and environmental factors, including calcium intake, may thus help to understand the discordant relationships between BMD and VDR gene polymorphisms.
维生素D受体（VDR）基因多态性是否与骨质疏松症相关存在高度争议。然而，VDR基因多态性与骨密度（BMD）之间的关系可能会受到年龄相关和/或环境因素的影响。我们研究了青春期前至绝经前女性BMD与VDR基因型之间的潜在关联，并前瞻性地调查了VDR基因型与儿童期膳食钙及BMD变化之间的相互作用。对369名年龄在7至56岁的健康白种女性（143名青春期前女孩、54名青春期及青春期后青少年和172名绝经前成年人）进行了Bsm I VDR基因多态性以及腰椎（LS）和股骨（颈[FN]和骨干[FS]）BMD的评估。还对101名参与了一项为期1年的关于补钙（850毫克/天）与安慰剂对骨矿物质积累影响的双盲随机研究的青春期前女孩测量了股骨转子（FT）和桡骨远端BMD（干骺端和骨干）。在所有女性中，150名（40.7%）具有bb、167名（45.3%）具有Bb、52名（14%）具有BB VDR基因型。在青春期前和青春期女孩中，LS BMD（Z评分）与VDR基因型相关，BB基因型的女孩显著低于Bb或bb基因型的女孩。在FN水平以及所测量的三个部位（LS、FN和FS）的平均BMD（Z评分）上也检测到了类似差异的趋势。相比之下，在成年人中，各VDR基因型之间未检测到BMD差异。在101名前瞻性研究的青春期前女孩中，补钙显著增加了大多数骨骼部位的BMD，但LS除外。按VDR基因型分类（40名bb、47名Bb和14名BB）后，补钙对Bb基因型女孩有显著影响，对bb基因型女孩则无显著影响，而对BB基因型女孩，补钙有正向但不显著的影响趋势。此外，膳食钙摄入量与Bb基因型女孩不同独立骨部位的BMD变化显著相关，而与bb基因型女孩无关。相反，当膳食钙摄入量较低时，即不补钙时，bb基因型女孩的BMD增加似乎高于其他基因型。仅在青春期前，BMD与VDR基因多态性显著相关，BB基因型女孩的BMD（Z评分）显著低于其他基因型。通过增加膳食钙摄入量，青春期前Bb基因型女孩以及可能还有BB基因型女孩的BMD积累增加，而bb基因型个体的自发BMD积累最高，且不受补钙影响。因此，考虑到VDR基因多态性与包括钙摄入量在内的环境因素之间的复杂相互作用，可能有助于理解BMD与VDR基因多态性之间不一致的关系。
