Anabolic and Catabolic Pathways of Parathyroid Hormone on the Skeleton

Parathyroid hormone (PTH) is essential for the maintenance of the serum calcium concentration within narrow, normal limits, a feat that is achieved, in part, by its ability to regulate bone resorption. In addition to this traditional catabolic role, the osteoanabolic actions of PTH are also well known. Clinically, the catabolic effect of PTH is best represented by primary hyperparathyroidism (PHPT), whereas its osteoanabolic effect is best seen when PTH or its biological amino-terminal fragment [PTH(1–34)] is used as a therapy for osteoporosis. At the cellular level, PTH favors bone resorption, mostly by affecting the RANKL–OPG–RANK system and ultimately increasing both osteoclast recruitment and osteoclast activity. On the osteoanabolic level, PTH increases bone formation, a feat mediated, in part, by control of sclerostin, a regulator of the osteoanabolic Wnt signaling pathway. This chapter focuses on the cellular bases by which PTH exerts these dual anabolic and catabolic actions on the skeleton.