Introduction

The genetic and physiological relationships between the two calciotropic hormones, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP), and their roles in bone growth and calcium homeostasis will be reviewed. Present understanding of the regulation of calcium homeostasis and skeletal development at the molecular level has been derived in part from an analysis of the effects of disruption or overexpression of particular genes in humans or animals. Such loss of function or gain of function may be either naturally occurring or experimentally induced. The ongoing elucidation of the roles of the calciumsensing receptor (CaSR) in calcium homeostasis and of PTHrP and the PTH/PTHrP receptor in skeletogenesis provides a good example of this.

Overview of calcium homeostasis

Keeping the concentration of the extracellular fluid calcium concentration within a narrow normal range is critical for many physiological processes, including neuromuscular activity, and normal skeletal development and maintenance. The parathyroid gland plays a central role in calcium homeostasis by sensing a decrease in the blood calcium concentration and responding by synthesizing and secreting more PTH (Fig. 6.1). PTH acts on the kidney to enhance renal calcium reabsorption and to promote the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D [1,25-(OH)2D]. This hormonally active metabolite of vitamin D increases gastrointestinal absorption of calcium and, with PTH, induces skeletal resorption, causing an increase in the circulating calcium concentration.