Osteoporosis-treating parathyroid hormone peptides: What are they? What do they do? How might they do it? 2006

James F Whitfield
Institute for Biological Sciences, The National Research Council of Canada, Building M-54, Montreal Road Campus, Ottawa, Ontario, K1A 0R6, Canada. pthosteo@rogers.com

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.

UI MeSH Term Description Entries
D010024 Osteoporosis Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis. Age-Related Osteoporosis,Bone Loss, Age-Related,Osteoporosis, Age-Related,Osteoporosis, Post-Traumatic,Osteoporosis, Senile,Senile Osteoporosis,Osteoporosis, Involutional,Age Related Osteoporosis,Age-Related Bone Loss,Age-Related Bone Losses,Age-Related Osteoporoses,Bone Loss, Age Related,Bone Losses, Age-Related,Osteoporoses,Osteoporoses, Age-Related,Osteoporoses, Senile,Osteoporosis, Age Related,Osteoporosis, Post Traumatic,Post-Traumatic Osteoporoses,Post-Traumatic Osteoporosis,Senile Osteoporoses
D010281 Parathyroid Hormone A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates. Natpara,PTH (1-84),PTH(1-34),Parathormone,Parathyrin,Parathyroid Hormone (1-34),Parathyroid Hormone (1-84),Parathyroid Hormone Peptide (1-34),Hormone, Parathyroid
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D001846 Bone Development The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS. Bone Growth
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071679 Glycogen Synthase Kinase 3 beta A glycogen synthase kinase-3 type enzyme that functions in ENERGY METABOLISM; EMBRYONIC DEVELOPMENT; and NEUROGENESIS. It is also involved in PROTEIN BIOSYNTHESIS and regulates cell growth and proliferation as a component of the WNT SIGNALING PATHWAY and other signaling pathways. Certain polymorphisms in the GSK3B gene have been associated with PARKINSON DISEASE; ALZHEIMER DISEASE; and BIPOLAR DISORDER. GSK-3beta,GSK3B Protein,GSK3beta,GSK 3beta
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014057 Tomography, X-Ray Computed Tomography using x-ray transmission and a computer algorithm to reconstruct the image. CAT Scan, X-Ray,CT Scan, X-Ray,Cine-CT,Computerized Tomography, X-Ray,Electron Beam Computed Tomography,Tomodensitometry,Tomography, Transmission Computed,X-Ray Tomography, Computed,CAT Scan, X Ray,CT X Ray,Computed Tomography, X-Ray,Computed X Ray Tomography,Computerized Tomography, X Ray,Electron Beam Tomography,Tomography, X Ray Computed,Tomography, X-Ray Computer Assisted,Tomography, X-Ray Computerized,Tomography, X-Ray Computerized Axial,Tomography, Xray Computed,X Ray Computerized Tomography,X Ray Tomography, Computed,X-Ray Computer Assisted Tomography,X-Ray Computerized Axial Tomography,Beam Tomography, Electron,CAT Scans, X-Ray,CT Scan, X Ray,CT Scans, X-Ray,CT X Rays,Cine CT,Computed Tomography, Transmission,Computed Tomography, X Ray,Computed Tomography, Xray,Computed X-Ray Tomography,Scan, X-Ray CAT,Scan, X-Ray CT,Scans, X-Ray CAT,Scans, X-Ray CT,Tomographies, Computed X-Ray,Tomography, Computed X-Ray,Tomography, Electron Beam,Tomography, X Ray Computer Assisted,Tomography, X Ray Computerized,Tomography, X Ray Computerized Axial,Transmission Computed Tomography,X Ray Computer Assisted Tomography,X Ray Computerized Axial Tomography,X Ray, CT,X Rays, CT,X-Ray CAT Scan,X-Ray CAT Scans,X-Ray CT Scan,X-Ray CT Scans,X-Ray Computed Tomography,X-Ray Computerized Tomography,Xray Computed Tomography
D015519 Bone Density The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS. Bone Mineral Content,Bone Mineral Density,Bone Densities,Bone Mineral Contents,Bone Mineral Densities,Density, Bone,Density, Bone Mineral
D044168 Receptor, Parathyroid Hormone, Type 1 A parathyroid hormone receptor subtype that recognizes both PARATHYROID HORMONE and PARATHYROID HORMONE-RELATED PROTEIN. It is a G-protein-coupled receptor that is expressed at high levels in BONE and in KIDNEY. Parathyroid Hormone Receptor Type 1,PTH-PTHrP Receptor,PTH-Related Peptide Receptor,PTH-Related Protein Receptor,PTHLP Receptor,PTHrP Receptor,Parathyroid Hormone Receptor,Parathyroid Hormone Receptor 1,Parathyroid Hormone Receptor Type I,Parathyroid Hormone-Like Peptide Receptor,Parathyroid Hormone-Related Peptide Receptor,Receptor, Parathyroid Hormone-Like Peptide,PTH PTHrP Receptor,PTH Related Peptide Receptor,PTH Related Protein Receptor,Parathyroid Hormone Like Peptide Receptor,Parathyroid Hormone Related Peptide Receptor,Receptor, PTH-PTHrP,Receptor, PTH-Related Peptide,Receptor, PTH-Related Protein,Receptor, PTHLP,Receptor, PTHrP,Receptor, Parathyroid Hormone

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