A large-scale random sample cohort study for planning preventive procedures of osteoporosis allowing for genetic risks

我们对从日本不同地区的三个市的居民中随机选择的1，650名日本妇女进行了基线后3年的随访研究。两项研究均包括骨矿物质密度（BMD）测量，生活方式因素的详细访谈和维生素D受体（VDR）基因型的测定。1285例（80%）完成随访，结果表明：（1）绝经前后骨丢失最大的部位是脊柱和前臂。然而，在股骨颈，70岁及以上的受试者表现出最大的损失。(2)体重增加、体力活动量增加、牛奶摄入量增加、膳食钙摄入量增加、经常食用发酵大豆“纳豆”和不吸烟是减少骨丢失的因素。(3)我们确定了VDR基因3端和5端多态性的基因型。等位基因频率与日本人的相似。然而，这两种多态性对BMD均无显著影响。(4)基因型和生活方式因素对骨密度的影响有显著的交互作用。运动对3-末端多态性为tt和Tt基因型的受试者的BMD有有益的影响，而摄入牛奶对5-末端多态性为FF和Ff基因型的受试者的BMD有有益的影响。然而，在本研究中观察到的VDR基因型和生活方式因素的显着相互作用表明，骨质疏松症的预防程序可以为具有特定基因型的个体设计，这可能会导致在不久的将来量身定制的预防。

We performed a follow-up study 3 years after the baseline on 1,650 Japanese women randomly selected from the inhabitants of three municipalities in different areas in Japan. Both studies comprised bone mineral density (BMD) measurement, detailed interviews on lifestyle factors and determination of the vitamin D receptor (VDR) genotype. 1285 subjects (80%) completed the follow-up study.The results obtained were as follows :(1) The greatest bone loss was observed around the age at menopause at the spine and forearm. At the femoral neck, however, the subjects aged 70 years and older showed the greatest loss.(2) Factors suggested to reduce bone loss were as follows : heavier weight, higher physical activity, greater intake of milk, greater intake of dietary calcium, frequent intake of fermented soybean "natto" and non-smoking.(3) We determined genotypes of 3-end and 5-end polymorphisms of the VDR gene. The allele frequency was similar to the previously reported for Japanese. However, either of the polymorphism did not show a significant effect on BMD.(4) Some significant interactions of the genotypes and lifestyle factors on BMD were observed. Exercise had a beneficial effect on BMD in the subjects with genotypes defined as tt and Tt at 3-end polymorphism and intake of milk did so in those with the genotypes FF and Ff at 5-end polymorphism.Genetic factors may play a less role in determining the bone mass after the acquisition of the peak bone mass in comparison with lifestyle factors. However, significant interactions of the VDR genotype and lifestyle factors observed in the present study suggest that preventive procedures for osteoporosis could be designed for an individual with a particular genotype, which may lead to tailor-made prevention in near future.