Genetic and Environmental Factors Affecting Peak Bone Mass in Premenopausal Japanese Women

ABSTRACT

The purpose of this study was to examine the relationships between peak bone mass and genetic and environmental factors. We measured whole-body bone mineral density (BMD), lumbar spine BMD, and radius BMD with dual-energy X-ray absorptiometry (DXA) and analyzed eight genetic factors vitamin D receptor (VDR)-3', VDR-5', estrogen receptor (ER), calcitonin receptor (CTR), parathyroid hormone (PTH), osteocalcin (OC), apolipoprotein E (ApoE), and fatty acid binding protein 2 (FABP2) allelic polymorphisms using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs). We also surveyed menstrual history, food intake, and history of physical activity using questionnaires. After adjusting for age, body mass index (BMI), current smoking status, current Ca intake, alcohol intake, menoxenia, and physical activity, the mean BMD in subjects with the HH/Hh genotype was significantly higher than that of subjects with the hh genotype for whole-body BMD (mean±SD, 1.20±0.10 vs. 1.18 ±0.09 g/cm2; HH/Hh vs. hh, p=0.04) and at lumbar spine BMD (mean±SD, 1.18±0.14 vs. 1.14±0.12 g/cm2; HH/Hh vs. hh, p=0.02) in OC allelic polymorphism. Furthermore, the results of multiple regression analyses taking the 8 genetic factors plus the 7 environmental factors listed above into account showed that the strongest factor contributing to BMD was BMI at any site (whole-body and lumbar BMD p<0.0001, radius BMD p=0.0029). In addition, OC polymorphism (p=0.0099), physical activity (p=0.0245), menoxenia (p=0.0384), and PTH polymorphism (p=0.0425) were independent determinants for whole-body BMD, and OC polymorphism (p=0.0137) and physical activity (p=0.0421) were independent determinants for lumbar BMD and radius BMD, respectively.