Osteoporosis-treating parathyroid hormone peptides: What are they? What do they do? How might they do it?
The first experiments demonstrating parathyroid hormone's (PTH's) dramatic bone-building activity in rat pups, using a bovine parathyroid extract called parathormone were reported 74 years ago. Over the next decades, the native parathyroid hormone (human (h)PTH(1-84)) was purified and two of its fragments (hPTH(1-34) and (Leu27)cycloGlu22-Lys26hPTH(1-31)NH2) have been developed for the treatment of osteoporosis. One of these, recombinant (r)hPTH(1-34), is now on the market under the trade name of Forteo. The native hormone has also completed clinical trials and (Leu27)cycloGlu22-Lys26hPTH(1-31)NH2 is in phase II clinical trials under the trade name Ostabolin-C. All three of these peptides potently stimulate bone growth, reinforce bone microstructure weakened by estrogen deprivation and reduce further fracturing. Furthermore, future studies may demonstrate that these peptides also promote the repair of existing fractures and implant anchorage in both healthy and osteoporotic humans. PTHs have the potential to become more successful by using cost-cutting, but still effective, cyclical treatment regimens and by formulating them for non-injectable delivery. This review will discuss the identification of PTH peptides, how they function and their future role in the treatment of osteoporosis.
Whitfield
James F
JF
Institute for Biological Sciences, The National Research Council of Canada, Building M-54, Montreal Road Campus, Ottawa, Ontario, K1A 0R6, Canada. pthosteo@rogers.com
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000502:physiology; D014057:Tomography, X-Ray Computed; D051176:beta Catenin / Q000502:physiology
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D044168:Receptor, Parathyroid Hormone, Type 1; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3