VITAMIN-D-RECEPTOR GENE POLYMORPHISMS ARE NOT RELATED TO BONE TURNOVER, RATE OF BONE LOSS, AND BONE MASS IN POSTMENOPAUSAL WOMEN - THE OFELY STUDY

Vitamin D receptor (VDR) gene polymorphisms have been reported to acco unt for most of the well established genetic influence on bone mineral density (BMD). However, discordant studies have been published and it is still not clear whether VDR genotypes influence bone mass accretio n and/or postmenopausal bone loss. In this study, we analyzed VDR gene polymorphisms, i.e., that of BsmI, ApaI, and TaqI restriction enzymes in 268 untreated postmenopausal women 1-26 years postmenopausal. Ther e were 37 BBAA homozygote (absence of BsmI and ApaI restriction sites on both alleles), 55 bbaa homozygote (presence of restriction sites on both alleles), and 176 heterozygotes. At baseline, women between the three genotypes did not differ significantly in age, years since menop ause, body mass index (BMI), nor dietary calcium intake. We found no r elationship between VDR genotypes and bone turnover assessed by three serum markers of bone formation and three urinary bone resorption mark ers, nor with BMD measured at the spine, hip, forearm, and whole body by dual-energy X-ray absorptiometry (DXA). Rates of bone loss assessed by repeated DXA measurements over 2 years were highly significant (p = 0.02-0.0001) at all skeletal sites except for the lumbar spine but d id not differ between genotypes at any sites either before or after ad justment for potential confounding factors such as years since menopau se, BMI, calcium intake, serum 25 hydroxyvitamin D levels, and baselin e BMD. When we restricted the analysis to early postmenopausal women, within 10 years of menopause (n = 128), lumbar spine bone loss became significant, but no significant difference between VDR genotypes in th e rate of bone loss measured at any site was found. We conclude that V DR genotypes are not predictive of bone turnover, rate of postmenopaus al bone loss, and bone mass in either early or late postmenopausal wom en. In a subgroup of women with a low calcium intake (below 600 mg/day ), we also found no significant differences between genotypes in BMD a nd the rate of bone loss measured at any site, although the sample siz e (n = 64) may be too small to detect small differences. In conclusion , these data, along with the absence of relationships between VDR gene polymorphisms and peak bone mass that we recently reported, suggest t hat the determination of VDR genotypes is probably not a useful clinic al test for the risk assessment of osteoporosis.