Selected extraskeletal effects of systemic treatment with basic fibroblast growth factor in ovariectomized rats.
Basic fibroblast growth factor (bFGF) is a pleiotropic mitogen with a potent bone-forming effect, rendering it a potential osteoporosis therapy. This study examined selected extraskeletal effects of bFGF in ovariectomized rats, a well-established model of human postmenopausal osteopenia, to more fully characterize side effects associated with bFGF treatment. Five-month-old, osteopenic, ovariectomized rats were injected subcutaneously with vehicle or bFGF (1 mg/kg) daily for 3 weeks. Hematologic and biochemical analyses were performed; and kidneys, livers, and proximal tibiae were examined histologically and histomorphometrically. bFGF administration resulted in anemia that was due to a shift toward granulocyte production in the bone marrow. Increased granulocyte production was also observed in the liver of bFGF-treated rats, which exhibited a markedly increased number and area of hematopoietic foci. bFGF administration also caused mild glomerular hypertrophy that was not attended by significant biochemical evidence of glomerular dysfunction. The bone anabolic effect of subcutaneous bFGF administration was confirmed in the proximal tibia, and was associated with a significant decrease in urine fractional excretion of calcium in bFGF-treated rats. Though bFGF strongly stimulates bone formation at osteopenic skeletal sites, its extraskeletal effects may restrict the long-term use of bFGF in its current form as an osteoporosis therapy.
Wamsley
Heather L
HL
Department of Pathobiology, College of Veterinary Medicine, Veterinary Medical Teaching Hospital, Clinical Pathology Service, University of Florida, Gainesville, Florida 32610, USA. wamsleyh@mail.vetmed.ufl.edu
Iwaniec
Urszula T
UT
Wronski
Thomas J
TJ
D000740:Anemia / Q000209:etiology; D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000378:metabolism*; D002118:Calcium / Q000652:urine; D004195:Disease Models, Animal; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects; D006411:Hematopoiesis, Extramedullary / Q000187:drug effects; D007279:Injections, Subcutaneous; D010012:Osteogenesis / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D016222:Fibroblast Growth Factor 2; D002118:Calcium