A developmental genetic approach to understanding skeletal metabolism and anatomy

Abstract

The most obvious function of the skeleton is to provide support and protection for the body. Its role as an endocrine organ is well recognized but extends from providing a valuable reservoir of minerals – notably calcium and phosphate – to include functions in regulating global energy homeostasis, particularly in altering insulin sensitivity. Healthy bone undergoes extensive remodelling throughout life through the action of bone-resorbing osteoclasts and bone-forming osteoblasts coordinated by osteocytes embedded in the bone matrix that sense the stresses acting on the skeleton. Genetic factors play a key role in many processes of bone development and regulation. Investigation of animal models and rare human genetic diseases has yielded major insights into many aspects of bone biology, which in some cases has led to the development of new strategies for treating metabolic bone diseases (e.g. osteoporosis, X-linked hypophosphataemia). The process of bone mineralization is incompletely understood but involves local regulation of inorganic phosphate and pyrophosphate ratios as well as other local inhibitors of phosphate mineralization. This article gives examples of some of the genetic factors that cause abnormal bone metabolism, including osteoporosis, osteomalacia, hyperostosis and ectopic ossification.