Histopathological study on bone changes induced by recombinant granulocyte colony-stimulating factor in rats.
Histopathological bone changes were examined in growing rats intravenously administered with high doses (100 and 1000 micrograms/kg/day) of recombinant human granulocyte colony-stimulating factor (rG-CSF) for 28 days. The changes were observed in the region where physiological bone resorption actively occurs in the growth phase, that is the trabeculae of metaphyseal spongy bone and the endosteum region of diaphyseal compact bone. Histologically, the changes involved accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification. While osteoclastic bone resorption was observed in almost all lesions, about half of which were accompanied by osteogenesis. Bone changes which appeared after administration of rG-CSF were characterized by frequent occurrence at the site of highly osteoclastic activity and by initial osteoclastic resorption followed by osteogenesis due to intramembranous ossification. These results suggest that the main action of rG-CSF on bone may be an acceleration of osteoclastic bone resorption.
Suzuki
M
M
Toxicology Research Laboratory, Chugai Pharmaceutical Co., Ltd., Nagano, Japan.
Sakamaki
Y
Y
Miyoshi
A
A
Adachi
K
K
Usami
M
M
Nakayama
H
H
Doi
K
K
D000818:Animals; D001835:Body Weight; D001847:Bone Diseases / Q000139:chemically induced* / Q000473:pathology*; D001853:Bone Marrow / Q000473:pathology; D001862:Bone Resorption / Q000139:chemically induced / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology*; D005260:Female; D005269:Femur; D016179:Granulocyte Colony-Stimulating Factor / Q000633:toxicity*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008684:Metatarsus; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000633:toxicity
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor