Effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on rat bone: inhibition of bone formation at the endosteal surface of vertebra and tibia.
The effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on bone was evaluated by histomorphometry using Sprague-Dawley rats. rh G-CSF was injected at doses of 0, 50, 150, and 450 microg/kg for 6 weeks. In vivo double fluorochrome labeling was performed before sacrifice. No significant change in body weight was observed. Bone mineral density (BMD) of lumbar vertebrae and femora was significantly decreased in G-CSF-treated groups. In the lumbar vertebra, osteoid surface, osteoid thickness, trabecular thickness, and labeled surface in G-CSF-treated groups were also significantly lower. In addition, osteoclast number and osteoclast surface were significantly higher in the G-CSF-treated groups. The endocortical surface at the mid-tibia showed lower labeled surface and mineral apposition rate in G-CSF-treated groups, without significant changes at the periosteal surface. Furthermore, numerous granulocytes fully occupied the bone marrow area. We conclude that proliferating granulocytes in the bone marrow may inhibit bone-forming cells from contacting the bone surface, resulting in reduction of bone formation; and increased osteoclastic bone resorption induced by G-CSF treatment contributed to the reduction of BMD.
Soshi
S
S
Department of Orthopedic Surgery, Niigata University School of Medicine, Niigata City, Japan 951.
Takahashi
H E
HE
Tanizawa
T
T
Endo
N
N
Fujimoto
R
R
Murota
K
K
D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000187:drug effects*; D005269:Femur; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D008159:Lumbar Vertebrae; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013977:Tibia
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor