Summary Bone mineral density (BMD) reflects both genetic and lifestyle factors. The aim of this cross-sectional study was to investigate the influence of vitamin D receptor ( VDR ) gene polymorphism and lifestyle factors on BMD in premenopausal female workers. The subjects were 162 premenopausal female employees aged 22-44 y who worked at a large-scale integrated manufacturing facility in Japan. BMD was measured at the nondominant radius by dual energy X-ray absorptiometry. Lifestyle information was obtained by a questionnaire at the same time and genomic DNA was isolated from peripheral leukocytes. BMD was positively correlated with age, weight, and body mass index (BMI). The genotype frequencies of VDR gene polymorphism detected by Taq I analysis were 77.2, 22.8, and 0.0% for TT , Tt , and tt , respectively. Analysis of covariance with adjustment for age and BMI showed that the mean BMD was significantly lower in subjects with the Tt genotype than in those with the TT genotype. Subjects who drank alcohol also showed a significantly lower BMD if they had the Tt genotype than if they had the TT genotype. According to multiple linear regression analysis, the independent determinants of BMD were age, BMI, and VDR gene polymorphism. Our data show that BMD is negatively correlated with the Tt genotype of the VDR gene, but positively correlated with age and BMI. These findings suggest that analysis of VDR gene polymorphism may be useful for identifying individuals who are susceptible to osteoporosis so that early preventive measures can be provided. Key Words bone mineral density, gene polymorphism, lifestyle factors, vitamin D receptor In Japan, prevention of osteoporosis is a high-priority issue because osteoporotic fracture is one of the primary causes of elderly persons becoming bedridden ( 1 ). Measurement of bone mineral density (BMD) is the best tool available to assess osteoporotic fracture risk, since low BMD is an important risk factor for osteoporotic fracture ( 2 ). The peak BMD of Japanese women is reached around 35-40 y of age, and it falls rapidly during the first 10 y after menopause and then decreases gradually ( 3 ). Because a decrease of BMD is inevitable after menopause, it is necessary to identify and manage any premenopausal decrease of BMD. BMD can be influenced by various lifestyle factors, such as smoking, alcohol intake, exercise, and nutrition ( 4 ). Among the genes that may be associated with the development of osteoporosis, polymorphism of the vitamin D receptor ( VDR ) gene has been most widely studied ( 5 ), and a meta-analysis ( 6 ) suggested that BMD is influenced by VDR gene polymorphism. BMD is affected by both genetic and lifestyle factors ( 5 ), but most studies have separately investigated the effects of VDR gene polymorphism or lifestyle factors on BMD. Better understanding of this combined effect may allow us to identify a highrisk group for osteoporosis and lead to more effective osteoporosis prevention and to improvement of public health. A few previous studies ( 7-10 ) have ...