Parathyroid hormone: anabolic and catabolic actions on the skeleton

Abstract

Parathyroid hormone (PTH) is essential for the maintenance of calcium homeostasis through, in part, its actions to regulate bone remodeling. While PTH stimulates both bone formation and bone resorption, the duration and periodicity of exposure to PTH governs the net effect on bone mass, that is whether it is catabolic or anabolic. PTH receptor signaling in osteoblasts and osteocytes can increase the RANKL/OPG ratio, increasing both osteoclast recruitment and osteoclast activity, and thereby stimulating bone resorption. In contrast, PTH-induced bone formation is explained, at least in part, by its ability to downregulate SOST/sclerostin expression in osteocytes, permitting the anabolic Wnt signaling pathway to proceed. The two modes of administration of PTH, that is, continuous vs. intermittent, can regulate, in bone cells, different sets of genes; alternatively, the same sets of genes exposed to PTH in sustained vs. transient way, will favor bone resorption or bone formation, respectively. This article reviews the effects of PTH on bone cells that lead to these dual catabolic and anabolic actions on the skeleton.