Department of Oral Biology, University of Missouri - Kansas City School of Dentistry, 650 East 25th Street, Kansas City, MO 64108, USA.
Genome Med. 2009 Sep 7;1(9):84. doi: 10.1186/gm84.
Osteoporosis is a skeletal disorder characterized by compromised bone strength that predisposes a person to an increased risk of fracture. Osteoporosis is a complex trait that involves multiple genes, environmental factors, and gene-gene and gene-environment interactions. Twin and family studies have indicated that between 25% and 85% of the variation in bone mass and other skeletal phenotypes is heritable, but our knowledge of the underlying genes is limited. Bone mineral density is the most common assessment for diagnosing osteoporosis and is the most often used quantitative value in the design of genetic studies. In recent years, our understanding of the pathophysiology of osteoporosis has been greatly facilitated by advances brought about by the Human Genome Project. Genetic approaches ranging from family studies of monogenic traits to association studies with candidate genes, to whole-genome scans in both humans and animals have identified a small number of genes that contribute to the heritability of bone mass. Studies with transgenic and knockout mouse models have revealed major new insights into the biology of many of these identified genes, but much more needs to be learned. Ultimately, we hope that by revealing the underlying genetics and biology driving the pathophysiology of osteoporosis, new and effective treatment can be developed to combat and possibly cure this devastating disease. Here we review the rapidly evolving field of the genomics of osteoporosis with a focus on important gene discoveries, new biological/physiological paradigms that are emerging, and many of the unanswered questions and hurdles yet to be overcome in the field.
骨质疏松症是一种骨骼疾病，其特征是骨强度受损，使患者骨折风险增加。骨质疏松症是一种复杂的特征，涉及多个基因、环境因素以及基因-基因和基因-环境相互作用。双胞胎和家族研究表明，骨骼表型的骨量和其他特征的 25%至 85%的变化是可遗传的，但我们对潜在基因的了解有限。骨矿物质密度是诊断骨质疏松症最常用的评估方法，也是遗传研究设计中最常用的定量值。近年来，人类基因组计划带来的进展极大地促进了我们对骨质疏松症病理生理学的理解。遗传方法从单基因特征的家族研究到候选基因的关联研究，再到人类和动物的全基因组扫描，已经确定了少数几个基因对骨量的遗传性有贡献。使用转基因和基因敲除小鼠模型的研究揭示了许多已识别基因的生物学的新的重要见解，但仍有许多需要了解。最终，我们希望通过揭示导致骨质疏松症病理生理学的潜在遗传学和生物学，开发出新的有效治疗方法来对抗甚至可能治愈这种破坏性疾病。在这里，我们将重点介绍重要的基因发现、新兴的新生物学/生理学范例，以及该领域尚未解决的许多问题和障碍，来回顾骨质疏松症基因组学这一快速发展的领域。
