Vitamin D receptor gene allelic variants, bone density, and bone turnover in community-dwelling men

The role of vitamin D receptor (VDR) gene polymorphisms in the determination of bone mass and bone turnover is controversial in women. The aim of the study was to determine whether VDR polymorphisms are associated with indices of bone mineral density (BMD) (by dual-energy X-ray absorptiometry and by ultrasound) and/or with bone turnover and muscle strength, factors related to both BMD and fracture risk. For this purpose, we investigated a cohort of community-dwelling men >70 years (n = 271) and a group of healthy control subjects between the ages of 20 and 50 years (n = 137). VDR TaqI, ApaI, and FokI genotypes were determined using enzymatic restriction digestion of polymerase chain reaction (PCR) fragments. In the elderly group, the lowest BMD value at the femoral neck and at the calcaneus was observed in subjects with the "At-At" haplotype genotype, with differences between extreme haplotype groups ("At-At" vs. noncarriers of the "At" allele) ranging from 5.8% to 34.3% (p < or = 0.05). Moreover, at the different subregions of the distal forearm and the tibia, the lowest BMD estimates were consistently associated in both elderly and younger men with the "At" haplotype allele, although this did not approach statistical significance. Elderly subjects with the "At-At" genotype had a significantly higher serum osteocalcin level. BMD was not significantly related to the FokI VDR polymorphism at any of the assessed skeletal sites, nor were any of the biochemical markers associated with the FokI VDR genotype. There were no differences between genotype groups for any of the indices of muscle strength. The present study indicates that the VDR genotype is associated with BMD in healthy community-dwelling elderly men and tends to be associated with biochemical markers, particularly of bone formation, in elderly men.