HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Iida-Klein, A Articles by Lindsay, R Search for Related Content PubMed PubMed Citation Articles by Iida-Klein, A Articles by Lindsay, R

¹ Regional Bone and
² Clinical Research Centers, Helen Hayes Hospital, West Haverstraw, New York, USA
³ Scanco USA Inc., Wayne, Pennsylvania, USA
⁴ Departments of Clinical Pathology and
⁵ Medicine, Columbia University, College of Physicians and Surgeons, New York, New York, USA

(Requests for offprints should be addressed to A Iida-Klein, Helen Hayes Hospital, Regional Bone Center, 51-55 N Route 9W, West Haverstraw, NY 10993, USA; Email: iida-kleina{at}helenhayeshosp.org)

Parathyroid hormone (PTH) stimulates bone resorption as well as bone formation in vivo and in organ culture. The catabolic actions of PTH have been recognized in patients with hyperparathyroidism, or with acute infusion of the N-terminal 1–34 fragment of human PTH (hPTH1–34). Whereas the anabolic actions of daily injection with PTH have been well studied in both humans and mice, the catabolic actions of PTH on murine bone remain to be defined. To do this we sought to create a model with short-term, sustained hyperparathyroidism using osmotic infusion pumps. We treated 10-week-old female C57BL/J6 mice with continuous infusion of hPTH1–34 (8.1 pmol/0.25 µl per h, equivalent to 40 µg/kg per day) or vehicle for 2 weeks, using Alzet osmotic pumps. Bone mineral density (BMD), serum total calcium, hPTH1–34, mouse intact PTH (mPTH1–84), osteocalcin and mouse tartrate-resistant acid phosphatase (mTRAP) activity, and microarchitectural variables of the distal femur were measured. Separately, we compared the effects of intermittent daily injection of hPTH1–34 (40 µg/kg per day) with continuous infusion of hPTH1–34 on BMD and bone markers. Exogenous hPTH1–34 was detected only in the PTH-infused mice. Both intermittent and continuous treatment with hPTH1–34 markedly suppressed endogenous mPTH1–84, but only the latter induced hypercalcemia. Daily PTH injection significantly increased both serum osteocalcin and mTRAP, while continuous PTH infusion showed a strong trend to stimulate mTRAP, with a slight but non-significant increase in osteocalcin. There were significant differences in BMD at all sites between animals treated with the same daily dose of intermittent and continuous hPTH1–34. Microcomputed tomography (µCT) analysis of the distal femurs revealed that hPTH1–34 infusion significantly decreased trabecular connectivity density (P<0.05). Thus, the murine bone response to continuous PTH infusion was quite different from that seen with daily PTH injection. Short-term infusion of hPTH1–34 appears to be a good model to study the mechanisms underlying the catabolic action of PTH in mice.

This article has been cited by other articles:

				S. Johnston, S. Andrews, V. Shen, F. Cosman, R. Lindsay, D. W. Dempster, and A. Iida-Klein The Effects of Combination of Alendronate and Human Parathyroid Hormone(1 34) on Bone Strength Are Synergistic in the Lumbar Vertebra and Additive in the Femur of C57BL/6J Mice Endocrinology, September 1, 2007; 148(9): 4466 - 4474. [Abstract] [Full Text] [PDF]

				M. S. Huang, S. Morony, J. Lu, Z. Zhang, O. Bezouglaia, W. Tseng, S. Tetradis, L. L. Demer, and Y. Tintut Atherogenic Phospholipids Attenuate Osteogenic Signaling by BMP-2 and Parathyroid Hormone in Osteoblasts J. Biol. Chem., July 20, 2007; 282(29): 21237 - 21243. [Abstract] [Full Text] [PDF]