Although some studies have reported a relationship between several candidate polymorphic genes and bone mineral density (BMD), little is known concerning the genetic factors influencing BMD in children. This study examined this relationship in healthy Japanese girls (n=125; age, 13.4 +/- 0.89 years; range, 12-15 years). We investigated allelic variants of the vitamin D receptor (VDR) gene, the estrogen receptor (ER) gene, the parathyroid hormone (PTH) gene, the Ca-sensing receptor (CaSR) gene, and the beta3-adrenergic receptor (beta3-AR) gene. The genotype of the VDR gene (Fok I) correlated with lumbar spine, and femoral neck BMD. The PTH polymorphisms (BstB I, Dra II) were also associated with lumbar spine BMD. No relationship was found between genotypes of the ER gene, CaSR gene, or beta3-AR gene and BMD. The age, height, weight, and body mass index did not differ significantly among girls with different VDR and PTH genotypes. These results suggest that the Fok I polymorphism of the VDR gene and the Dra II polymorphism of the PTH gene are risk factors for low bone density in Japanese girls.