Developments in parathyroid hormone and related peptides as bone-formation agents.
Osteoporosis is a major and growing healthcare concern. When administered by daily injection, parathyroid hormone (PTH) and its N-terminal fragments and analogs are potent bone-formation agents. Teriparatide, recombinant human PTH(1-34), is likely to be the first anabolic agent approved for treating osteoporosis, despite inducing osteosarcomas in rats. Native PTH and other PTH fragments and analogs are also in development. N-terminal fragments sometimes differ in activity from the native hormone, however, and the C-terminal region of PTH, acting through a receptor different from the classical PTH-1 receptor, initiates a variety of distinct biological activities. In particular, the C-terminal region of PTH, by promoting bone-cell apoptosis, may be important in opposing the anti-apoptotic effects of teriparatide in these cells, thereby maintaining normal bone-cell turnover. Because of these differences, care must be taken to consider the effects of native PTH and N-terminal PTH fragments and analogs separately.
Fox
John
J
NPS Pharmaceuticals, Inc., 420 Chipeta Way, Salt Lake City, UT 84108, USA. jfox@npsp.com
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001862:Bone Resorption / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy; D012516:Osteosarcoma / Q000139:chemically induced / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology* / Q000627:therapeutic use*; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D019379:Teriparatide / Q000627:therapeutic use
D010281:Parathyroid Hormone; D010455:Peptides; D019379:Teriparatide