Basic Aspects of PTH in Skeletal Health

We review in vivo studies of parathyroid hormone (PTH) anabolic actions at the cellular and molecular level, include updated information obtained from genetically modified mice, and new information on human skeletal responses to PTH that now better guides the use of animal models. Molecular mechanisms that underlie the anabolic effects of PTH are still not fully understood. Trabecular bone increases as bone formation processes dominate. This response has been intensively studied in mice and rats. Lifetime treatment of rats at higher doses increased the frequency of osteosarcoma, but the relevance of this finding to humans remains unknown. Cortical bone mass may increase or remain unchanged, as both bone resorption and bone formation are stimulated in remodeling of osteonal bone. The net effect is to increase bone strength. This response has been best demonstrated in rabbits and monkey models. In PTH-responsive osteoporotic humans, the complex of responses translate into reduction in fracture rate.