| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Division of Endocrinology (M.J.H., M.B.T., A.G.-O., A.F.S.), The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213; and Department of Orthopedics (C.G.), Yale University School of Medicine, New Haven, Connecticut 06520
Address all correspondence and requests for reprints to: Andrew F. Stewart, M.D., Division of Endocrinology, BST E-1140, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, Pennsylvania 15213. E-mail: stewart{at}msx.dept-med.pitt.edu.
PTH-related protein (PTHrP) is homologous with PTH. PTH, an effective anabolic agent for treating osteoporosis, has been shown to stimulate both bone resorption by osteoclasts and bone formation by osteoblasts. We examined whether PTHrP might share anabolic properties in osteoporosis. A 3-month double-blind, prospective, placebo-controlled, randomized clinical trial was performed in 16 healthy postmenopausal women with osteoporosis. All received calcium and vitamin D, and all continued their prior hormone replacement therapy. One group also received daily sc PTHrP (6.56 µg/kg·d, or approximately 400 µg/d), and the other group received placebo injections.
The PTHrP group displayed a 4.7% increase in lumbar spine bone mineral density (BMD) and also demonstrated an increase in osteoblastic bone formation, as assessed using serum osteocalcin measurements. In contrast, there was no increase in bone-specific alkaline phosphatase and collagen-1 propeptide or either of two markers of osteoclastic bone resorption, N-telopeptide, or deoxypyridinoline. One subject in the placebo group withdrew from the study, but there were no significant adverse events in the PTHrP group.
PTHrP administered sc in high doses for only 3 months appears to be a potent anabolic agent, producing a 4.7% increase in lumbar spine BMD. This compares very favorably to available antiresorptive drugs for osteoporosis and is similar to the increases in BMD at this early time point reported for PTH. Despite the high doses, PTHrP was well tolerated. Larger clinical trials are required to confirm these results and fully assess the anabolic potential of PTHrP in osteoporosis.
This work was supported by NIH Grants DK 55081 and AR 38460.
Abbreviations: BMD, Bone mineral density; DPD, deoxypyridinoline; NS, not significant; NTX, N-telopeptide; P1CP, collagen-1 propeptide; PTHrP, PTH-related protein.
This article has been cited by other articles:
 |
|
 |
|
  T. J. Gardella Mimetic Ligands for the PTHR1: Approaches, Developments, and Considerations IBMS BoneKEy, February 1, 2009; 6(2): 71 - 85. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. F. Nemeth Anabolic Therapy for Osteoporosis: Calcilytics IBMS BoneKEy, June 1, 2008; 5(6): 196 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. Mundy and J. R. Edwards PTH-Related Peptide (PTHrP) in Hypercalcemia J. Am. Soc. Nephrol., April 1, 2008; 19(4): 672 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dean, J.-P. Vilardaga, J. T. Potts Jr., and T. J. Gardella Altered Selectivity of Parathyroid Hormone (PTH) and PTH-Related Protein (PTHrP) for Distinct Conformations of the PTH/PTHrP Receptor Mol. Endocrinol., January 1, 2008; 22(1): 156 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Canalis, A. Giustina, and J. P. Bilezikian Mechanisms of Anabolic Therapies for Osteoporosis N. Engl. J. Med., August 30, 2007; 357(9): 905 - 916. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fuentes, P. M. Guerreiro, T. Modesto, J. Rotllant, A. V. M. Canario, and D. M. Power A PTH/PTHrP receptor antagonist blocks the hypercalcemic response to estradiol-17beta Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R956 - R960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Dean, A. Linglart, M. J. Mahon, M. Bastepe, H. Juppner, J. T. Potts Jr., and T. J. Gardella Mechanisms of Ligand Binding to the Parathyroid Hormone (PTH)/PTH-Related Protein Receptor: Selectivity of a Modified PTH(1-15) Radioligand for G{alpha}S-Coupled Receptor Conformations Mol. Endocrinol., April 1, 2006; 20(4): 931 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Godler, A. N. Stein, O. Bakharevski, M. M. L. Lindsay, and P. F. J. Ryan Parathyroid hormone-related peptide expression in rat collagen-induced arthritis Rheumatology, September 1, 2005; 44(9): 1122 - 1131. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bisello, M. J. Horwitz, and A. F. Stewart Parathyroid Hormone-Related Protein: An Essential Physiological Regulator of Adult Bone Mass Endocrinology, August 1, 2004; 145(8): 3551 - 3553. [Full Text] [PDF]
|
|
|
|
|
|
D. Miao, J. Li, Y. Xue, H. Su, A. C. Karaplis, and D. Goltzman Parathyroid Hormone-Related Peptide Is Required for Increased Trabecular Bone Volume in Parathyroid Hormone-Null Mice Endocrinology, August 1, 2004; 145(8): 3554 - 3562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Stossi, D. H. Barnett, J. Frasor, B. Komm, C. R. Lyttle, and B. S. Katzenellenbogen Transcriptional Profiling of Estrogen-Regulated Gene Expression via Estrogen Receptor (ER) {alpha} or ER{beta} in Human Osteosarcoma Cells: Distinct and Common Target Genes for These Receptors Endocrinology, July 1, 2004; 145(7): 3473 - 3486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Wilson New Treatments for Growing Scourge of Brittle Bones Ann Intern Med, January 20, 2004; 140(2): 153 - 156. [Full Text] [PDF]
|
|
|
|
 |
|
 S.P. Barros, M.A.D. Silva, M.J. Somerman, and F.H. Nociti Jr. Parathyroid Hormone Protects against Periodontitis-associated Bone Loss Journal of Dental Research, October 1, 2003; 82(10): 791 - 795. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
