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Histomorphometric analysis of the effects of standard heparin on trabecular
bone in vivo
JM Muir, M Andrew, J Hirsh, JI Weitz, E Young, P Deschamps and SG Shaughnessy
Department of Pathology, McMaster University, Ontario, Canada.
Long-term heparin treatment causes osteoporosis through an as yet undefined
mechanism. To investigate this phenomenon, we treated rats with once daily
subcutaneous injections of heparin (in doses ranging from 0.25 to 1.0 U/g)
or saline for 8 to 32 days and monitored the effects on bone both
histomorphometrically and by serial measurements of urinary type 1 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 showed that heparin induces both a time- and
dose-dependent decreased in trabecular bone volume, with the majority of
trabecular bone loss occurring within the first 8 days of treatment. Thus,
heparin doses of 1.0 U/g/d resulted in a 32% loss of trabecular bone.
Heparin-treated rats also showed a 37% decrease in osteoblast surface as
well as a 75% decrease in osteoid surface. In contrast, heparin treatment
had the opposite effect on osteoclast surface, which was 43% higher in
heparin- treated rats, as compared with that in control rats. Biochemical
markers of bone turnover showed that heparin treatment produced a dose-
dependent decrease in serum alkaline phosphatase and a transient increase
in urinary PYD, thus confirming the histomorphometric data. Based on these
observations, we conclude that heparin decreases trabecular bone volume
both by decreasing the rate of bone formation and increasing the rate of
bone resorption.
Volume 88,
Issue 4,
pp. 1314-1320,
08/15/1996
Copyright © 1996 by The American Society of Hematology
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