|
|
 Previous Article | Table of Contents | Next Article 
A histomorphometric comparison of the effects of heparin and low-
molecular-weight heparin on cancellous bone in rats
JM Muir, J Hirsh, JI Weitz, M Andrew, E Young and SG Shaughnessy
Department of Pathology, McMaster University and the Hamilton Civic
Hospitals Research Centre, Ontario, Canada.
Long-term heparin treatment causes osteoporosis through, an as yet,
undefined mechanism. To investigate this phenomenon and to determine the
relative benefits of low-molecular-weight heparin (LMWH) use, we treated
rats with once daily subcutaneous injections of either unfractionated
heparin (1.0 U/g or 0.5 U/g), the LMWH, Tinzaparin (1.0 U/g or 0.5 U/g), or
placebo (saline) for a period of 32 days. The effects on bone were then
compared both histomorphometrically and biochemically by measuring urinary
type I collagen cross-linked pyridinoline (PYD) and serum alkaline
phosphatase, markers of bone resorption and formation, respectively.
Histomorphometric analysis of the distal third of the right femur, in the
region proximal to the epiphyseal growth plate, demonstrated that both
heparin and LMWH decrease cancellous bone volume in a dose-dependent
fashion, but that heparin causes significantly more cancellous bone loss
than does LMWH. Although both heparin and LMWH decrease osteoblast and
osteoid surface to a similar extent, only heparin increases osteoclast
surface. In support of these histomorphometric findings, biochemical
markers of bone turnover demonstrated that both heparin and LMWH treatment
produce a dose-dependent decrease in serum alkaline phosphatase, consistent
with reduced bone formation, whereas only heparin causes a transient
increase in urinary PYD, consistent with an increase in bone resorption.
Based on these observations, we conclude that heparin decreases cancellous
bone volume both by decreasing the rate of bone formation and increasing
the rate of bone resorption. In contrast, LMWH, causes less osteopenia than
heparin because it only decreases the rate of bone formation.
Volume 89,
Issue 9,
pp. 3236-3242,
05/01/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
B. Giannakopoulos and S. A. Krilis
How I treat the antiphospholipid syndrome
Blood,
September 3, 2009;
114(10):
2020 - 2030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Hirsh, K. A. Bauer, M. B. Donati, M. Gould, M. M. Samama, and J. I. Weitz
Parenteral Anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Chest,
June 1, 2008;
133(6_suppl):
141S - 159S.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
T. Kelly, L. J. Suva, Y. Huang, V. MacLeod, H.-Q. Miao, R. C. Walker, and R. D. Sanderson
Expression of Heparanase by Primary Breast Tumors Promotes Bone Resorption in the Absence of Detectable Bone Metastases
Cancer Res.,
July 1, 2005;
65(13):
5778 - 5784.
[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]
|
|
|
|
|
|
|
J. I. Weitz
New Anticoagulants for Treatment of Venous Thromboembolism
Circulation,
August 31, 2004;
110(9_suppl_1):
I-19 - I-26.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W Streif, G Goebel, A K C Chan, and M P Massicotte
Use of low molecular mass heparin (enoxaparin) in newborn infants: a prospective cohort study of 62 patients
Arch. Dis. Child. Fetal Neonatal Ed.,
September 1, 2003;
88(5):
F365 - F370.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. J. Caine and G. Y. H. Lip
Is Low-Molecular-Weight Heparin Safer Than Warfarin for Secondary Prevention of Venous Thromboembolism in Cancer Patients?
Arch Intern Med,
May 26, 2003;
163(10):
1243 - 1244.
[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]
|
|
|
|
|
|
|
N. Murashige and R. F. Schneider
Extended Out-of-Hospital Low-Molecular-Weight Heparin for Prophylaxis against Deep Venous Thrombosis
Ann Intern Med,
October 1, 2002;
137(7):
620 - 621.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Walton, J. M. Duncan, P. Deschamps, and S. G. Shaughnessy
Heparin acts synergistically with interleukin-11 to induce STAT3 activation and in vitro osteoclast formation
Blood,
September 18, 2002;
100(7):
2530 - 2536.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. Kock and A. E. Handschin
Osteoblast Growth Inhibition by Unfractionated Heparin and by Low Molecular Weight Heparins: An in-vitro Investigation
Clinical and Applied Thrombosis/Hemostasis,
July 1, 2002;
8(3):
251 - 255.
[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
(2009):
64S - 94S.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Ginsberg, I. Greer, and J. Hirsh
Use of Antithrombotic Agents During Pregnancy
Chest,
January 1, 2001;
119
(2009):
122S - 131S.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Mocetti, P. Ballanti, S. Zalzal, G. Silvestrini, E. Bonucci, and A. Nanci
A Histomorphometric, Structural, and Immunocytochemical Study of the Effects of Diet-induced Hypocalcemia on Bone in Growing Rats
J. Histochem. Cytochem.,
August 1, 2000;
48(8):
1059 - 1078.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
R. L. Bick and E. P. Frenkel
Clinical Aspects of Heparin-Induced Thrombocytopenia and Thrombosis and Other Side Effects of Heparin Therapy
Clinical and Applied Thrombosis/Hemostasis,
October 1, 1999;
5(1_suppl):
S7 - S15.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. G. Shaughnessy, J. Hirsh, M. Bhandari, J. M. Muir, E. Young, and J. I. Weitz
A Histomorphometric Evaluation of Heparin-Induced Bone Loss After Discontinuation of Heparin Treatment in Rats
Blood,
February 15, 1999;
93(4):
1231 - 1236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. Dhodapkar, E. Abe, A. Theus, M. Lacy, J. K. Langford, B. Barlogie, and R. D. Sanderson
Syndecan-1 Is a Multifunctional Regulator of Myeloma Pathobiology: Control of Tumor Cell Survival, Growth, and Bone Cell Differentiation
Blood,
April 15, 1998;
91(8):
2679 - 2688.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
