Endocrinology of bone and growth disorders

Multiple dynamic cellular events underlie de novo bone formation. Osteoblasts synthesis, and deposit an extracellular matrix, which together with phosphatases participate in matrix mineralization and the formation of bone. The skeleton affords a number of diverse functions such as a biomechanical and protective scaffold, calcium and phosphorus homeostasis and linear growth. To enable these roles, bones must be of the correct shape, size and structure and able to faithfully renew themselves in order to maintain a healthy, robust and structurally functional skeleton. These functions are finely tuned by local and endocrine factors but when errors occur in the activity of osteoblasts, osteocytes, osteoclasts and epiphyseal chondrocytes both skeletal and growth abnormalities occur. This article will focus on the physiology, pathophysiology and clinical treatments of endocrine, paracrine and autocrine disorders that disrupt the bone remodeling balance which in some cases predispose the skeleton to increased risk of fracture. Such disorders include primary and secondary osteoporosis, Paget's disease, osteopetrosis, hypophosphatasia and nutritional and vitamin D resistant rickets. We also consider the causes and therapeutic options available for a number of growth disorders such as achondroplasia and growth hormone deficiency, which lead to aberrant linear growth and compromised final height.