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The age-related difference in bone changes in rats induced by recombinant human granulocyte colony-stimulating factor
M Suzuki1, Y Sakamaki, A Miyoshi
1Toxicology Research Laboratory, Chugai Pharmaceutical Co., Ltd., Nagano, Japan.
Abstract:
We examined the bone changes in recombinant granulocyte colon-stimulating factor (rhG-CSF)-treated young and young adult rats in order to investigate the effect of age-related conditions of bone growth on the bone changes induced by rhG-CSF. Recombinant human G-CSF (100 and 1,000 micrograms/kg/day) was given to rats by daily intravenous injection for 28 days starting at the age of either 6 or 14 wk, and the hindlimb bones were evaluated histopathologically. In the young rats, bone lesions were observed in the 100- and 1,000-micrograms/k groups. In the young adult rats, lesions were found only in the 1,000-micrograms/kg group. The lesions involved accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification and there was no age-related difference in these histopathological findings. However, both the incidence of bone involvement and the severity of lesions were greater in the young rats than in the dose-matched young adult rats. The results suggest that the higher dose of rhG-CSF may intrinsically induce bone lesions of a particular histopathological nature in rats regardless of their age, and the action of rhG-CSF on bone may be stronger in young growing rats than in young adults.