Growth Plate, Bone and Mineral Metabolism

Recent substantial advances in molecular genetic methodology have led to a rapid expansion of our knowledge and understanding of molecular mechanisms governing normal skeletal growth and homeostasis. The complexity of the regulatory networks and the number of players therein is remarkable. Several key pieces in this puzzle have been discovered by studies involving children with rare skeletal diseases, such as osteogenesis imperfecta or other skeletal dysplasias, or children with disturbed mineral metabolism, such as hypophosphatemic rickets. Understanding the pathophysiology and the molecular mechanisms leading to skeletal or mineral disorders provides a solid background for the development of specific therapies. During the past year several new genes in various skeletal conditions have been discovered, as seen in the selected papers. However, equally exciting is to see the increasing number of studies describing attempts to find therapies for these skeletal disorders, such as achondroplasia and hypochondroplasia caused by overactive FGF receptor, or hypophosphatemic disorders caused by increased FGF23. As shown in this chapter, the preliminary results are promising, but much work remains to be done before these therapies are available for patient care. While research on pathological conditions moves forward, several aspects in the skeletal physiology still remain poorly understood: How do bones grow? How do growth plate cells function without oxygen (or with little oxygen)? And what is the role of the osteocytes, the quiet bone cells entrapped within the mineralized matrix?