Peak bone mass is considered a major determinant in the emergence of osteoporosis and is mainly genetically regulated. Several genes have been investigated, among them the vitamin D receptor ( VDR) gene. A single-nucleotide polymorphism (defined by the endonuclease FokI) located in the start codon of the VDR creates the alleles F and f, resulting in different proteins. A number of previous studies have proved the F allele to be more advantageous as concerns bone mineral density (BMD). In this longitudinal study of 88 adolescent boys, we have investigated whether the different genotypes are associated with BMD, bone mineral content (BMC), or bone area. BMD, BMC, and bone area of the right femoral neck, lumbar spine, and total body were measured using dual-energy X-ray absorptiometry. Differences in phenotypes in relation to the FokI polymorphism were calculated by means of an analysis of variance (ANOVA), with Bonferroni's correction for multiple comparisons. At the first examination, the FokI genotypes were significantly related to lumbar spine BMC and total body bone area in boys aged 16.9 +/- 0.3 years (mean +/- SD). There was a strong tendency towards significance as regards pubertal stage, total body and femoral neck BMC, weight, lean body mass, lumbar spine bone area, and lumbar spine BMD. There were no significant differences in height, fat mass, birth height and weight, total body and femoral neck BMD, and femoral neck bone area. Regression analysis proved the FokI genotypes to be independently related to lumbar spine BMD ( FF > ff; P < 0.01), and possibly total body BMD ( P = 0.06), but not femoral neck BMD. At the second examination, approximately 2 years later, our ANOVA results showed significance as regards femoral neck BMC and weight. Using multiple regression, the FokI genotypes were independently related to lumbar spine BMD ( FF > ff; P = 0.03), and total body BMD ( P < 0.05), but not femoral neck BMD. This study proves the FokI polymorphism to be an independent predictor of lumbar spine BMD are probably total body BMD, but not femoral neck BMD.