|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 4 (February 15), 1999:
pp. 1231-1236
A Histomorphometric Evaluation of Heparin-Induced Bone Loss After
Discontinuation of Heparin Treatment in Rats
Stephen G. Shaughnessy,
Jack Hirsh,
Mohit Bhandari,
Jeffrey M. Muir,
Edward Young, and
Jeffrey I. Weitz
From the Departments of Pathology and Medicine, McMaster University
and the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario,
Canada.
Although it is well established that long-term heparin therapy
causes osteoporosis, it is unknown whether heparin-induced bone loss is
reversible when heparin treatment is stopped. To address this question,
we randomized rats to once daily subcutaneous injections of either
unfractionated heparin (1.0 U/g or 0.5 U/g) or saline for 28 days and
then followed the rats for an additional 28 days off treatment. Based
on histomorphometric analysis of the distal third of the right femur
proximal to the epiphyseal growth plate, 1.0 U/g heparin caused a 30%
loss in cancellous bone volume over the first 28 days. This was
accompanied by a 137% increase in osteoclast surface and a 60%
decrease in both osteoblast and osteoid surface. One month after
cessation of heparin treatment, no recovery in these parameters was
observed. Similarly, serum levels of alkaline phosphatase, a
biochemical marker of bone formation, which continued to decrease over
the course of heparin treatment, showed no signs of recovery in the
subsequent 28 days off treatment. To explore the mechanism responsible
for the prolonged effect of heparin on bone, we repeated the experiment giving 125I-labeled heparin in place of unlabeled heparin.
125I-labeled heparin was found to accumulate in bone during
the course of its administration, and be retained in bone for at least
56 days after stopping heparin treatment. These findings suggest that
heparin-induced osteoporosis is not rapidly reversible because heparin
is sequestered in bone for an extended period.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. M. Bates, I. A. Greer, I. Pabinger, S. Sofaer, and J. Hirsh
Venous Thromboembolism, Thrombophilia, Antithrombotic Therapy, and Pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest,
June 1, 2008;
133(6_suppl):
844S - 886S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Rajgopal, M. Butcher, J. I. Weitz, and S. G. Shaughnessy
Heparin Synergistically Enhances Interleukin-11 Signaling through Up-regulation of the MAPK Pathway
J. Biol. Chem.,
July 28, 2006;
281(30):
20780 - 20787.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. F. Pineo and R. D. Hull
Low-Molecular-Weight Heparin for the Treatment of Venous Thromboembolism in the Elderly
Clinical and Applied Thrombosis/Hemostasis,
January 1, 2005;
11(1):
15 - 23.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. A. Smythe, W. E. Dager, and N. M. Patel
Managing Complications of Anticoagulant Therapy
Journal of Pharmacy Practice,
October 1, 2004;
17(5):
327 - 346.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. M. Bates, I. A. Greer, J. Hirsh, and J. S. Ginsberg
Use of Antithrombotic Agents During Pregnancy: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Chest,
September 1, 2004;
126(3_suppl):
627S - 644S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Bates and J. S. Ginsberg
How we manage venous thromboembolism during pregnancy
Blood,
November 15, 2002;
100(10):
3470 - 3478.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G Ruiz-Irastorza, M A Khamashta, C Nelson-Piercy, and G R. Hughes
Lupus pregnancy: is heparin a risk factor for osteoporosis?
Lupus,
September 1, 2001;
10(9):
597 - 600.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. Hirsh, T. E. Warkentin, S. G. Shaughnessy, S. S. Anand, J. L. Halperin, R. Raschke, C. Granger, E. M. Ohman, and J. E. Dalen
Heparin and Low-Molecular-Weight Heparin Mechanisms of Action, Pharmacokinetics, Dosing, Monitoring, Efficacy, and Safety
Chest,
January 1, 2001;
119(1_suppl):
64S - 94S.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Ginsberg, I. Greer, and J. Hirsh
Use of Antithrombotic Agents During Pregnancy
Chest,
January 1, 2001;
119(1_suppl):
122S - 131S.
[Full Text]
[PDF]
|
|
|
| |
