Publication: The development of bone changes induced in rats by recombinant human granulocyte colonystimulating factor is suppressed by bisphosphonate
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Date
1999
Authors
Suzuki, M. ; Adachi, K. ; Sugimoto, T. ; Nakayama, Hiroyuki ; Doi, K.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
We have previously demonstrated that high
doses of recombinant human granulocyte colonystimulating
factor (rhG-CSF) induce bone changes
characterized by osteoclastic bone resorption and
osteogenesis due to intramembranous ossification in rats.
In this communication we examined the effects of a
pretreatment with 3-amino-l-hydroxypropylidene-1,lbisphosphonate
(AHPrBP), which is a powerful inhibitor
of osteoclastic bone resorption, on bone changes induced
by rhG-CSF in order to investigate the relation between
osteoclastic bone resorption and osteogenesis. AHPrBP
(5 mg/kg/day) was subcutaneously given to 6-week-old
rats for 2 days. From the following day of the final
injection of AHPrBP, rats received a subcutaneous
injection of rhG-CSF (1,000 pg/kg/day) for 14 days, and
the femur and tibia were evaluated histopathologically.
By the analysis of peripheral blood leukocyte counts,
spleen weights and bone marrow findings, the
pretreatment with AHPrBP had no effect on the
activation of hematopoiesis related to the major
pharmacological activity of rhG-CSF. In the rats treated
with rhG-CSF alone, accelerated osteoclastic bone
resorption and osteogenesis due to intramernbranous
ossification were observed in the trabeculae of
metaphyseal spongiosa. The accelerated osteoclastic
bone resorption induced by rhG-CSF was suppressed by
the pharmacological activity of AHPrBP. Furthermore,
the osteogenesis induced by rhG-CSF was also suppressed by AHPrBP. These results suggest that the
osteogenesis induced by rhG-CSF is a sequential
reaction of accelerated osteoclastic bone resorption, and
moreover that the main action of rhG-CSF on bone is an
acceleration of osteoclastic bone resorption.
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